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Background/Objectives: Tumor-infiltrating lymphocytes (TILs) play a crucial role in the tumor microenvironment (TME), influencing the progression, prognosis, and response to treatment in oral squamous cell carcinoma (OSCC) and its precursors, oral potentially malignant disorders (OPMDs). This scoping review assesses the current literature on TILs in the TME of OSCC and OPMDs, aiming to identify trends and gaps in the research. Methods: A comprehensive search was performed in PubMed, using the following query terms: "Tumor Microenvironment AND (mouth neoplasms OR oral lichen OR leukoplakia OR oral lichenoid OR dysplasia OR GVHD OR lupus)". Based on the inclusion criteria, we selected in vivo human original research and clinical observational studies that focused on TILs within the TME of OSCC and OPMDs. Results: Out of 1152 results in PubMed, 58 studies were selected and analyzed. These studies investigated various TILs, including T cells, B cells, and natural killer (NK) cells. Of these, 47 studies focused on the OSCC TME, 4 examined the OPMDs ME, and 7 compared OSCC TME and OPMDs ME. Discussion: While TILs in OSCC have been extensively studied, research on infiltrating lymphocytes in OPMDs is still limited. In OSCC, CD8+ T cells, T helper 1 cells, and NK cells are associated with strong antitumor activity, whereas CD4+ T cells, including T helper 2 and regulatory T cells, are linked to protumoral effects. B cells remain less explored due to their low frequency in the TME. In OPMDs, trends suggest an increase in activated CD8+ T cells in OLP and lower NK cell numbers compared to OSCC, which may contribute to malignant transformation. Understanding the spatial distribution and activation status of TILs within the TME is essential for deciphering their role. The variability in TIL composition highlights the complexity of the TME. Conclusions: Current knowledge remains preliminary, though it highlights the crucial role of TILs in carcinogenesis and OSCC. A more in-depth understanding could improve diagnostic and therapeutic strategies, including the assessment of the risk of malignant transformation in OPMDs. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer occurs when cells grow uncontrollably, leading to the formation of tumors. This review examines how maintaining a balance of essential minerals, known as ions, in our cells influences the progression of cancer. It explains that normal levels of ions like sodium and calcium are necessary for healthy cell function. When ion levels are disrupted during cancer, it can lead to rapid cell growth and changes in genes. By restoring the right balance of these ions, we might be able to slow down the growth of both cancerous and normal cells, which could help improve cancer treatments and prevention methods. Cancer is a complex disease characterized by uncontrolled cell proliferation at various levels, leading to tumor growth and spread. This review focuses on the role of ion homeostasis in cancer progression. It describes a model of ion-mediated regulation in both normal and cancerous cell proliferation. The main function of this system is to maintain the optimal number of cells in the body by regulating intra- and extracellular ion content. The review discusses the key points of ion regulation and their impact on tumor growth and spread during cancer development. It explains that normal levels of sodium, potassium, calcium, chloride, and hydrogen ions are regulated at different levels. Damage to ion transport mechanisms during carcinogenesis can lead to an increase in sodium cations and water content in cells, disrupting the balance of calcium and hydrogen ions. This, in turn, can lead to chromatin compaction reduction, gene overexpression, and instability at the epigenetic and genomic levels, resulting in increased cell proliferation and mutagenesis. Restoring normal ion balance can reduce the proliferative potential of both normal and tumor cell populations. The proposed model of systemic ionic regulation of proliferation aims to reconcile diverse data related to cell mitotic activity in various physiological conditions and explain tumor growth. Understanding the mechanisms behind pathological cell proliferation is important for developing new approaches to control ion homeostasis in the body, potentially leading to more effective cancer treatment and prevention. [ABSTRACT FROM AUTHOR]

Simple Summary: Telomeres play an integral role in preventing genomic instability by protecting chromosomal ends using telomeric repeats, and their dysfunction may lead to premature aging disorders and age-related diseases. During cellular division, they undergo telomere attrition, resulting in the gradual shortening of those protective caps, leading to genomic instability and cellular aging. Critically short telomeres in normal cells trigger senescence, a major contributor to age-related diseases, and opens the door for genomic instability, which promotes carcinogenesis. This review aims to provide an updated overview of telomere biology and therapeutic strategies around telomere attrition. We emphasize the importance of understanding the complex balance between preserving telomere length in aging while inhibiting telomere maintenance in cancer by proposing Optimal Therapeutic Approaches based on the most updated literature. Background/Objectives: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer. The purpose of this review is to provide an updated overview of telomere biology and therapeutic tactics to address aging and cancer. Methods: We used the Rayyan platform to review the PubMed database and examined the ClinicalTrial.gov registry to gain insight into clinical trials and their results. Results: Cancer cells activate telomerase or utilize alternative lengthening of telomeres to escape telomere shortening, leading to near immortality. Contrarily, normal cells experience telomeric erosion, contributing to premature aging disorders, such as Werner syndrome and Hutchinson–Gilford Progeria, and (2) aging-related diseases, such as neurodegenerative and cardiovascular diseases. Conclusions: The literature presents several promising therapeutic approaches to potentially balance telomere maintenance in aging and shortening in cancer. This review highlights gaps in knowledge and points to the potential of these optimal interventions in preclinical and clinical studies to inform future research in cancer and aging. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with inflammatory bowel diseases (IBD) are at an increased risk of colorectal cancer (CRC) due to the chronic inflammation in the colon. This review examines potential strategies to prevent CRC in these patients, focusing on medications such as mesalazine, thiopurines, anti-TNF agents, and statins, as well as nutraceuticals and dietary interventions. These approaches aim to address inflammation and other mechanisms related to cancer in order to reduce CRC risk. Although many treatments show promise, further studies are needed to refine dosages, assess long-term safety, and investigate the combined use of different therapies. Regular colonoscopy and personalized prevention strategies are essential for lowering cancer risk and improving outcomes. Background: Inflammatory bowel diseases (IBDs) have been associated with a higher risk of colorectal cancer (CRC) development and chronic colonic inflammation seems to have a critical role in the pathogenesis of CRC in patients suffering from IBD. In respect to that, surveillance colonoscopy at regular intervals is recommended in patients with colitis. Objective: This review aims to explore the chemopreventive potential of a range of agents, including mesalazine, thiopurines, anti-TNF agents, statins, ursodeoxycholic acid, aspirin, folic acid, and nutraceuticals. Results: These agents target inflammation, oxidative stress, and oncogenic pathways, thereby offering the potential to reduce the risk of CRC in patients with IBD. Anti-TNF agents, such as infliximab and adalimumab, not only reduce colonic inflammation, but also play a protective role against CRC by lessening the carcinogenic effects associated with prolonged inflammatory processes. Furthermore, mesalazine and thiopurines have demonstrated established efficacy, while newer biologics, including interleukin inhibitors, show promising advancements. Although nutraceuticals and dietary interventions require further clinical validation, they offer additional possibilities for non-pharmacological prevention. Conclusion: Despite progress, knowledge gaps persist regarding the long-term safety, optimal dosing, and combined use of these agents. A significant reduction in the incidence of CRC in patients with IBD could be achieved by advancing chemoprevention and personalizing strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer initiation is not precisely defined yet. It should be the point of shift from normal/benign to malignant. However, it is still controversial in spite of the abundant accumulation of data on carcinogenesis. Cancer initiation is overviewed here from different viewpoints of genetics, epigenetics, viral/microbial infections, and chronic inflammation. The advent of cancer stem cells is discussed as the point at which a normal cell acquires malignancy. Exposure to radiation and chemicals, oncogenic viruses, microbiomes, and inflammation are the major events of cancer initiation. DNA damage and chromosomal aberrations are classically considered the main causes of cancer. The recent idea of epigenetics is broadening the concept, including the suggestion that oncogenic virus infection disrupts various intracellular signaling cascades. Chronic inflammation was proposed as the origin of cancer in the 19th century, and the molecular level of events has been made clear with scientific development. Much knowledge of cancer initiation has become available for integration into research. Simultaneously, the presence of cancer stem cells has been identified and characterized. However, the point of shift from normal to malignant still appears obscure even when taking cancer stem cells into consideration. From these points of view, the advent of cancer stem cells and cancer initiation are briefly discussed as the points of shift from normal to malignant in this paper. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence and mortality of anal cancer has risen in recent years. This longitudinal study over a ten-year period analyzed 2214 outpatient visits of 537 patients using high-resolution anoscopy (HRA)-based screening and standardized surveillance and treatment protocols. Dysplastic lesions were revealed in 49% of patients. While no invasive carcinomas developed during a median follow-up period of 48 months, 3% of HSIL patients progressed to carcinoma in situ. HIV-positive status showed an almost three-fold increased progression risk. The present study highlights the importance of dedicated screening, close surveillance, and early intervention in high-risk groups to reduce the risk of disease progression to anal cancer. In 2012, the Department of Visceral Surgery of the Lausanne University Hospital CHUV implemented a dedicated high-resolution anoscopy (HRA) outpatient clinic for surveillance and follow-up purposes. This 10-year longitudinal study analyzed 537 patients (2214 visits) using a structured screening protocol. Dysplastic lesions were detected in 49% of patients, predominantly low-grade squamous intraepithelial lesions (LSILs, 74%). Among LSIL cases, 6% progressed to high-grade squamous intraepithelial lesions (HSILs) within 24 months, reaching 25% cumulative progression at 36 months. Of HSIL patients, 3% developed carcinoma in situ after 48 months. Notably, no invasive carcinoma was observed during the follow-up. Four patients diagnosed with squamous cell carcinoma at initial screening were treated with chemoradiotherapy, and one required salvage surgery. Independent risk factors for the presence of higher-stage precancerous lesions (≥HSILs) were the presence of high-risk HPV genotypes (OR 14.5, 95% CI 5–42.2, p < 0.001), detectable HIV viral load (OR 5.4, 95% CI 1.8–16.7, p = 0.003), and symptoms at the first screening visit (OR 3.2, 95% CI 1.1–9.9, p = 0.04). HIV-positive status was associated with a trend towards an increased risk of progression (OR 2.79, p = 0.073). These findings highlight the importance of systematic follow-up and early intervention in high-risk populations to prevent anal cancer progression. [ABSTRACT FROM AUTHOR]

Simple Summary: The microbiota and Fusobacterium nucleatum (Fn) in particular are potential actors in oral oncology. The evidence about the role of Fn and the potential underlying mechanisms are reviewed on the basis of the more robust evidence concerning colorectal cancer. The translational potential of the different scenarios linking Fn to oral squamous cell carcinoma is discussed. Oral squamous cell carcinoma (OSCC) is one the most prevalent head and neck cancers and represents a major cause of morbidity and mortality worldwide. The main established risk factors for OSCC include tobacco and alcohol consumption and betel quid chewing, which may contribute alone or in combination with other environmental factors to carcinogenesis. The oral microbiota is emerging as a key player in the establishment of the molecular and cellular mechanisms that may trigger or promote carcinogenesis, including in the oral cavity. Among the bacterial species found in the oral microbiota, Fusobacterium nucleatum, an anaerobic bacterium commonly found in oral biofilms and a periodontal pathogen, has gained attention due to solid evidence implicating F. nucleatum in colorectal cancer (CRC). F. nucleatum has been shown to induce chronic inflammation, promote cell proliferation and trigger cellular invasion while deploying immune evasion mechanisms. These experimental findings were first obtained in in vitro and in vivo models of CRC and are being confirmed in studies on OSCC. In this review, we summarize the most recent findings on the role of F. nucleatum in OSCC, discuss the clinical implications in terms of prognosis and provide an overview of the key mechanisms involved. Moreover, we identify research questions and aspects that require investigations to clarify the role of F. nucleatum in OSCC. We anticipate that studies in this emerging field may have a significant clinical impact on the diagnosis, prognosis and management of OSCC. [ABSTRACT FROM AUTHOR]

Liver tumors represent a serious clinical health problem that threatens human life. Previous studies have demonstrated that the pathogenesis of liver tumors is complex and influenced by various factors, highlighting limitations in both basic pathological research and clinical treatment. Traditional research methods often begin with the discovery of phenomena and gradually progress to the development of animal models and human trials. Among these, liver tumor animal models play a critical role in advancing related research. The zebrafish liver closely resembles the human liver in structure, function, and regenerative capacity. Additionally, the high transparency and rapid development of zebrafish embryos and larvae make them ideal model organisms for studying liver tumors. This review systematically summarizes recent methods for constructing zebrafish liver tumor models, including transplantation, transgenesis, induction, and gene knockout. Furthermore, the present paper explores the applications of these models in the study of liver cancer pathogenesis, metastasis, the tumor microenvironment, drug screening, and other related areas. By comparing the advantages and limitations of various models and integrating their distinct characteristics, this review provides insights for developing a novel liver tumor model that better aligns with clinical needs. This approach will offer valuable reference information for further in-depth studies of the pathological mechanisms of liver tumors and the development of new therapeutic drugs or strategies. [ABSTRACT FROM AUTHOR]

Jun/JUN is a basic leucine zipper (bZIP) protein and a prototypic member of the activator protein-1 (AP-1) family of transcription factors that can act as homo- or heterodimers, interact with DNA elements and co-factors, and regulate gene transcription. Jun is expressed by both immune and inflammatory cells. Jun is traditionally seen as an oncoprotein that regulates processes involved in transformation and oncogenesis in human tumours. This article examines the traditional view that Jun plays a permissive role in cancer development and progression, whilst exploring emerging evidence supporting Jun's potential to prevent immune cell exhaustion and promote anti-tumour efficacy. [ABSTRACT FROM AUTHOR]

Background: Ionizing radiation (IR) is a well-known inducer of cellular senescence and the senescence-associated secretory phenotype (SASP). SASP factors play dual roles in cancer, either promoting or inhibiting its development. This study investigates IR-induced SASP factors specifically secreted by renal cortical epithelial (RCE) cells and their role in promoting renal cell carcinoma (RCC) progression. Methods: Proteomic data from the SASP Atlas were analyzed to identify IR-induced factors unique to RCE cells, with subsequent evaluations performed at both the gene and protein levels. Thirty-seven proteins were identified as exclusively upregulated and secreted by senescent RCE cells. Gene expression analysis of these RCE-specific SASP factors was conducted using the Gene Expression database of Normal and Tumor tissues (GENT2) and The Cancer Genome Atlas (TCGA). To assess their prognostic relevance in RCC, the corresponding proteins were further analyzed using the Human Protein Atlas (HPA), emphasizing the relationship between SASP factor expression and RCC progression. Results: ALDH18A1 and ASPH emerged as key RCE-specific SASP factors with significant upregulation at both the gene and protein levels (Log2 ratio > 1.15, p < 0.05). These proteins are implicated in pro-cancer activities and are strongly associated with poor prognostic outcomes in RCC. Their critical roles in RCC progression underscore their potential as promising therapeutic targets for the prevention and treatment of the disease. Conclusions: This study provides novel insights into the role of IR-induced SASP in renal carcinogenesis, marking the first identification of ALDH18A1 and ASPH as specific secreted proteins associated with tumor progression in RCC. This study suggests that ALDH18A1 and ASPH hold promise as early biomarkers for RCC and as therapeutic targets for disease prevention and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: Metabolites play a critical role within the tumor microenvironment (TME) by imposing changes on cell signaling, gene expression, and metabolic reprogramming of several tumor cell types. The TME has been found to impact the efficacy of emerging immunotherapies, and current work in the cancer metabolism space is focused on targeting the metabolic pathways that promote tumorigenesis and chemoresistance. This review summarizes recent discoveries in tumor metabolism and the impact metabolites have on altering cell signaling, preventing an effective immune response, and promoting tumor growth. Cancer cells must reprogram their metabolism to sustain rapid growth. This is accomplished in part by switching to aerobic glycolysis, uncoupling glucose from mitochondrial metabolism, and performing anaplerosis via alternative carbon sources to replenish intermediates of the tricarboxylic acid (TCA) cycle and sustain oxidative phosphorylation (OXPHOS). While this metabolic program produces adequate biosynthetic intermediates, reducing agents, ATP, and epigenetic remodeling cofactors necessary to sustain growth, it also produces large amounts of byproducts that can generate a hostile tumor microenvironment (TME) characterized by low pH, redox stress, and poor oxygenation. In recent years, the focus of cancer metabolic research has shifted from the regulation and utilization of cancer cell-intrinsic pathways to studying how the metabolic landscape of the tumor affects the anti-tumor immune response. Recent discoveries point to the role that secreted metabolites within the TME play in crosstalk between tumor cell types to promote tumorigenesis and hinder the anti-tumor immune response. In this review, we will explore how crosstalk between metabolites of cancer cells, immune cells, and stromal cells drives tumorigenesis and what effects the competition for resources and metabolic crosstalk has on immune cell function. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic inflammation is associated with the onset and progression of many non-human diseases including type-2 diabetes, coronary artery disease, and cancer. The effects of chronic inflammation in adult cancers are widely studied. However, pediatric cancers demonstrate significant genetic/epigenetic disparities from their adult counterparts, requiring separate classifications. Because of this, findings from adult malignancies cannot be applied to pediatrics cancers. In this review, we examine how chronic inflammation contributes to the unique genetic and epigenetic changes, tumor microenvironment, and immune response that underly pediatric cancers. Finally, we highlight current and developing therapies aimed at restoring inflammatory balance during and after treatment. Inflammation plays a crucial role in wound healing and the host immune response following pathogenic invasion. However, unresolved chronic inflammation can result in tissue fibrosis and genetic alterations that contribute to the pathogenesis of human diseases such as cancer. Recent scientific advancements exploring the underlying mechanisms of malignant cellular transformations and cancer progression have exposed significant disparities between pediatric and adult-onset cancers. For instance, pediatric cancers tend to have lower mutational burdens and arise in actively developing tissues, where cell-cycle dysregulation leads to gene, chromosomal, and fusion gene development not seen in adult-onset counterparts. As such, scientific findings in adult cancers cannot be directly applied to pediatric cancers, where unique mutations and inherent etiologies remain poorly understood. Here, we review the role of chronic inflammation in processes of genetic and chromosomal instability, the tumor microenvironment, and immune response that result in pediatric tumorigenesis transformation and explore current and developing therapeutic interventions to maintain and/or restore inflammatory homeostasis. [ABSTRACT FROM AUTHOR]

Simple Summary: Acute myeloid leukemia (AML) is a challenging blood cancer to treat, with only about 24% of patients surviving for 5 years after diagnosis. A key challenge is that AML cells stick to normal cells in the bone marrow (BM), and these BM cells protect them from chemotherapy. The aim of this project is to find drugs that disrupt AML cell adherence to BM cells and release them into the blood, where chemotherapy will be more effective. To achieve this, we have created a model of adhesive BM and shown that it mimics the drug resistance seen clinically. We have used the model as a testing platform for drugs that disrupt AML cell adhesion. We have shown that the combined targeting of CD44 and FAK, using anti-CD44 and the clinical-grade FAK inhibitor defactinib, inhibits the adhesion of the most primitive AML cells that are associated with drug resistance and disease relapse. Background/Objectives: Acute myeloid leukemia (AML) is an aggressive neoplasm. Although most patients respond to induction therapy, they commonly relapse due to recurrent disease in the bone marrow microenvironment (BMME). So, the disruption of the BMME, releasing tumor cells into the peripheral circulation, has therapeutic potential. Methods: Using both primary donor AML cells and cell lines, we developed an in vitro co-culture model of the AML BMME. We used this model to identify the most effective agent(s) to block AML cell adherence and reverse adhesion-mediated treatment resistance. Results: We identified that anti-CD44 treatment significantly increased the efficacy of cytarabine. However, some AML cells remained adhered, and transcriptional analysis identified focal adhesion kinase (FAK) signaling as a contributing factor; the adhered cells showed elevated FAK phosphorylation that was reduced by the FAK inhibitor, defactinib. Importantly, we demonstrated that anti-CD44 and defactinib were highly synergistic at diminishing the adhesion of the most primitive CD34high AML cells in primary autologous co-cultures. Conclusions: Taken together, we identified anti-CD44 and defactinib as a promising therapeutic combination to release AML cells from the chemoprotective AML BMME. As anti-CD44 is already available as a recombinant humanized monoclonal antibody, the combination of this agent with defactinib could be rapidly tested in AML clinical trials. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancers of the gastrointestinal (GI) tract are most aggressive, with poor prognosis and survival rates. The main factors that contribute to cancer development are genetic modifications, Helicobacter infection, gut dysbiosis, inflammation, and altered drug metabolism. Microbial metabolites like SCFA and secondary bile acids have dual roles, and a disruption in microbial balance may contribute to cancer progression. Understanding microbiota–tumour interactions is crucial in cancer therapies. Chronic inflammation promotes cancer progression and resistance to therapy, while acute inflammation activates antitumour activity. Significant pathways such as NF-κB, JAK-STAT, cGAS/STING, cytokines, chemokines and microbial metabolites control inflammation. Modern strategies in cancer treatment are use of recombinant cytokines, small-molecule inhibitors, and dendritic cell vaccines which target the signal pathways. Probiotics play a pivotal role in chemotherapy-induced gastroenteritis and in restoring gut microbiota balance. Moreover, reducing digestive disorders can improve the diversity of gut flora, improve thyroid hormone, and have antitumour activity by regulating the TLR4/MyD88/NF-κB pathway. Developing evidence emphasises on the gut microbiota's diagnostic and therapeutic potential in screening for colorectal cancer, treatment outcomes, and prevention strategies. Dysbiosis in the gut microbiota plays a significant role in GI cancer development by influencing immune function and disrupting metabolic functions. Dysbiosis can drive carcinogenesis through pathways like immune dysregulation and the release of carcinogenic metabolites, and altered metabolism, genetic instability, and pro-inflammatory signalling, contributing to GI cancer initiation and progression. Helicobacter pylori infection and genotoxins released from dysbiosis, lifestyle and dietary habits are other factors that contribute to GI cancer development. Emerging diagnostic and therapeutic approaches show promise in colorectal cancer treatment, including the multitarget faecal immunochemical test (mtFIT), standard FIT, and faecal microbiota transplantation (FMT) combined with PD-1 inhibitors. We used search engine databases like PubMed, Scopus, and Web of Science. This review discusses the role of dysbiosis in GI cancer onset and explores strategies such as FMT, probiotics, and prebiotics to enhance the immune response and improve cancer therapy outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Tumor-associated macrophages (TAMs) represent a challenge in developing an effective and safe therapy for HCC. TAMs are considered to be one of the major mechanisms for HCC resistance to current therapies. TAMs, known as M1-like and M2-like macrophages, were discovered to be subdivided into four subsets (M2a, M2b, M2c, and M2d). Each subset has a hypothetical contribution as a TAM immunosuppressive cell. Several trials have studied removing or modulating the immune suppressive roles of TAMs in the HCC microenvironment. Identifying TAMs' behavior and subsets may be crucial for modulating the immune suppression in the HCC microenvironment. Hepatocellular carcinoma (HCC) is a major global health issue characterized by poor prognosis and complex tumor biology. One of the critical components of the HCC tumor microenvironment (TME) is tumor-associated macrophages (TAMs), which play a pivotal role in modulating tumor growth, immune evasion, and metastasis. Macrophages are divided into two major subtypes: pro-inflammatory M1 and anti-inflammatory M2, both of which may exist in TME with altered function and proportion. The anti-inflammatory M2 macrophages are further subdivided into four distinct immune suppressive subsets. TAMs are generally counted as M2-like macrophages with altered immune suppressive functions that exert a significant influence on both cancer progression and the ability of tumors to escape immune surveillance. Their involvement in modulating immune responses via different mechanisms at the local and systemic levels has made them a key target for therapeutic interventions seeking to enhance treatment outcomes. How TAMs' depletion influences immune responses in cancer is the primary interest in cancer immunotherapies. The purpose of this review is to delve into the recent progress made in TAM-targeting therapies. We will explore the current theories, benefits, and challenges associated with TAMs' depletion or inhibition. The manuscript concludes with future directions and potential implications for clinical practice. [ABSTRACT FROM AUTHOR]

Cancer cells undergo remarkable metabolic changes to meet their high energetic and biosynthetic demands. The Warburg effect is the most well-characterized metabolic alteration, driving cancer cells to catabolize glucose through aerobic glycolysis to promote proliferation. Another prominent metabolic hallmark of cancer cells is their increased reliance on glutamine to replenish tricarboxylic acid (TCA) cycle intermediates essential for ATP production, aspartate and fatty acid synthesis, and maintaining redox homeostasis. In this context, mitochondria, which are primarily used to maintain energy homeostasis and support balanced biosynthesis in normal cells, become central organelles for fulfilling the heightened biosynthetic and energetic demands of proliferating cancer cells. Mitochondrial coordination and metabolite exchange with other cellular compartments are crucial. The human SLC25 mitochondrial carrier family, comprising 53 members, plays a pivotal role in transporting TCA intermediates, amino acids, vitamins, nucleotides, and cofactors across the inner mitochondrial membrane, thereby facilitating this cross-talk. Numerous studies have demonstrated that mitochondrial carriers are altered in cancer cells, actively contributing to tumorigenesis. This review comprehensively discusses the role of SLC25 carriers in cancer pathogenesis and metabolic reprogramming based on current experimental evidence. It also highlights the research gaps that need to be addressed in future studies. Understanding the involvement of these carriers in tumorigenesis may provide valuable novel targets for drug development. [ABSTRACT FROM AUTHOR]

Background and clinical significance: Viral infections are typically considered contributing or secondary factors in the development of breast cancer. Case presentation: This case report presents three instances of advanced breast cancer associated with triple viral infections. Case 1 involves a 78-year-old woman diagnosed with grade 2 invasive ductal carcinoma positive for HPV-18, CMV, and BLV. Case 2 describes a 39-year-old woman with grade 2 invasive ductal carcinoma, positive for HPV-16, CMV, and BLV. Case 3 is a 52-year-old woman with grade 3 invasive ductal carcinoma, positive for HPV-16, BLV, and MMTV. These cases suggest a possible correlation between viral co-infections and breast cancer aggressiveness, posing new questions about the role of viral infections in cancer development and prognosis. Conclusions: The findings contribute to growing evidence that viral infections may influence the progression and therapeutic response of breast cancer, warranting further investigation into targeted preventive measures including vaccinations. [ABSTRACT FROM AUTHOR]

Ubiquitin-conjugating enzyme E2 T (UBE2T) is a crucial E2 enzyme in the ubiquitin-proteasome system (UPS), playing a significant role in the ubiquitination of proteins and influencing a wide range of cellular processes, including proliferation, differentiation, apoptosis, invasion, and metabolism. Its overexpression has been implicated in various malignancies, such as lung adenocarcinoma, gastric cancer, pancreatic cancer, liver cancer, and ovarian cancer, where it correlates strongly with disease progression. UBE2T facilitates tumorigenesis and malignant behaviors by mediating essential functions such as DNA repair, apoptosis, cell cycle regulation, and the activation of oncogenic signaling pathways. High levels of UBE2T expression are associated with poor survival outcomes, highlighting its potential as a molecular biomarker for cancer prognosis. Increasing evidence suggests that UBE2T acts as an oncogene and could serve as a promising therapeutic target in cancer treatment. This review aims to provide a detailed overview of UBE2T's structure, functions, and molecular mechanisms involved in cancer progression as well as recent developments in UBE2T-targeted inhibitors. Such insights may pave the way for novel strategies in cancer diagnosis and treatment, enhancing our understanding of UBE2T's role in cancer biology and supporting the development of innovative therapeutic approaches. [ABSTRACT FROM AUTHOR]

The human endogenous retroviruses (HERVs) are ancient exogenous retroviruses that were embedded in the germline over 30 million years ago and underwent an endogenization process. They make up roughly 8% of the human genome. HERVs exhibit many physiological and non-physiological functions; for example, they play a role in the development of many diseases. They have been shown to affect carcinogenesis by modifying the expression of host genes through their functions as enhancers and promoters. Additionally, some molecules derived from HERVs may stimulate the immune system. Recently research has been focused on the effect of human endogenous retroviruses on the development of neurodegenerative diseases, including Alzheimer's disease (AD), which is the most common cause of dementia. AD is also linked to a significant deterioration in quality of life. The article aims to highlight the potential role of HERVs in neurodegenerative diseases such as Alzheimer's disease and senescence. Moreover, it is estimated that HERVs may be potential targets for diagnosis and therapy of AD. [ABSTRACT FROM AUTHOR]

Simple Summary: Iron is essential for many bodily functions, including energy production and immune defense. However, in cancer patients, both low and high iron levels can negatively impact disease progression and treatment effectiveness. Iron deficiency can weaken the immune system, reducing the effectiveness of therapies that rely on immune responses. On the other hand, excess iron can promote tumor growth and create an environment that protects cancer cells from treatments. This review explores how managing iron levels in cancer patients may improve treatment outcomes, aiming to guide future research and help develop better strategies for personalized cancer care. Iron metabolism plays a dual role in cancer, serving as an essential nutrient for cellular functions and a potential catalyst for tumor growth and immune evasion. Here, we cover the complex interplay between iron levels within the serum or in the microenvironment and cancer therapy, focusing on how iron deficiency and overload can impact immune function, tumor progression, and treatment efficacy. On the one hand, we highlight iron deficiency as a factor of primary immune responses and its adverse effects on anti-cancer immunotherapy efficacy. On the other hand, we also stress the impact of iron overload as an essential factor contributing to tumor growth, creating a suppressive tumor microenvironment that hinders immune checkpoint inhibitor immunotherapy. Overall, we emphasize the necessity of the personalized management of iron levels in oncology patients as a critical element in treatment optimization to achieve favorable outcomes. Based on these considerations, we believe that close and careful monitoring and the tailored balancing of iron supplementation strategies should be the subject of further clinical studies, and routine iron management should be implemented in oncology clinical practice and integrated into cancer therapy protocols. [ABSTRACT FROM AUTHOR]

The evolution of man on Earth took place under conditions of constant exposure to background ionizing radiation (IR). From this point of view, it would be reasonable to hypothesize the existence of adaptive mechanisms that enable the human organism to safely interact with IR at levels approximating long-term natural background levels. In some situations, the successful operation of molecular mechanisms of protection against IR is observed at values significantly exceeding the natural background level, for example, in cancer cells. In 15–25% of cancer patients, cancer cells develop a phenotype that is resistant to high doses of IR. While further investigations are warranted, the current evidence suggests a strong probability of observing positive health effects, including an increased lifespan, a reduced cancer risk, and a decreased incidence of congenital pathologies, precisely at low doses of ionizing radiation. This review offers arguments primarily based on a phenomenological approach and critically reconsidering existing methodologies for assessing the biological risks of IR to human health. Currently, in the most economically developed countries, there are radiation safety rules that interpret low-dose radiation as a clearly negative environmental factor. Nowadays, this approach may pose significant challenges to the advancement of radiomedicine and introduce complexities in the regulation of IR sources. The review also examines molecular mechanisms that may play a key role in the formation of the positive effects of low-dose IR on human radioadaptive capabilities. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive analysis of mitochondrial DNA (mtDNA) variations in dogs diagnosed with primary and recurrent tumours, employing Oxford Nanopore Technologies (ONT) for sequencing. Our investigation focused on mtDNA extracted from blood and tumour tissues of three dogs, aiming to pinpoint polymorphisms, mutations, and heteroplasmy levels that could influence mitochondrial function in cancer pathogenesis. Notably, we observed the presence of mutations in the D-loop region, especially in the VNTR region, which may be crucial for mitochondrial replication, transcription, and genome stability, suggesting its potential role in cancer progression. The study is pioneering in its use of long-read sequencing to explore the mutational landscape of mtDNA in canine tumours, revealing that while the overall mutational load did not differ between primary and recurrent tumours, specific changes in m.16168A/G, m.16188G/A, and m.16298A/G are linked with tumour tissues. Interestingly, the heteroplasmy outside the D-loop region was not specific to tumour tissues and did not provoke any malignant damage in protein-coding sequences, which in turn may be a tolerant effect of the reactive oxygen species (ROS) cellular stress mechanism. [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with HER2-positive breast cancer, the goal of neoadjuvant therapy is to achieve a pathological complete response (pCR). However, half of patients have residual invasive disease at definitive surgery after neoadjuvant treatment. For these patients, T-DM1, a drug that combines trastuzumab with a chemotherapy agent, is employed in the adjuvant setting to reduce the risk of recurrence. This study primarily aimed to evaluate the tolerability of T-DM1 in these patients in a real-world setting, with a secondary focus on its effectiveness. Among 410 patients treated across multiple Italian cancer centers, more than half experienced side effects, with a small proportion developing more severe adverse events. In terms of effectiveness, the median follow-up period and number of recurrence events were insufficient to allow for a formal analysis. Consequently, extended follow-up is necessary to fully understand the long-term impact of T-DM1 in routine clinical practice. Background/Objectives: HER2-positive breast cancer (HER2+BC) is an aggressive subtype, with neoadjuvant treatment (NAT) aiming to achieve a pathological complete response (pCR) to improve long-term outcomes. Trastuzumab emtansine (T-DM1) has been established as the standard of care in the adjuvant setting for HER2+BC patients who do not obtain pCR. The ATD study aimed to evaluate the real-world tolerability of T-DM1 in this setting. The secondary objective was to assess the effectiveness. Methods: This was a multicenter, retrospective study across 24 Italian oncology centers, including 410 patients with HER2+BC treated with adjuvant T-DM1 following a lack of pCR after NAT. Patient characteristics, NAT regimens, and surgical outcomes were recorded. Tolerability was assessed by documenting adverse events (AEs) according to the CTCAE (v5.0). Preliminary effectiveness was evaluated in terms of relapse-free survival (RFS) and overall survival (OS). Results: Overall, 228 patients (55.6%) experienced at least one AE related to T-DM1, with 4.9% experiencing grade 3 or higher AEs. The most common AEs were hepatotoxicity (18.5%) and thrombocytopenia (17.6%). T-DM1 was discontinued in 10.0% of patients due to toxicity. After a median follow-up of 25 months, 31 relapse events (7.6%) and 22 deaths (5.4%) were reported. The preliminary incidence of RFS and OS events was similar between patients who completed the T-DM1 course and those who discontinued it early. Conclusions: T-DM1 demonstrated a manageable safety profile, and the adverse events were consistent with those reported in randomized trials. The data are not yet sufficient to allow for a formal analysis of RFS and OS, and long-term follow-up is required. [ABSTRACT FROM AUTHOR]

Simple Summary: Pancreatic ductal adenocarcinoma (PDAC) is a highly aggressive and often deadly cancer with limited treatment options. Sirtuins, a group of NAD+-dependent enzymes, have recently been identified as key players in PDAC progression and therapy resistance. Each sirtuin has a distinct role in PDAC biology. SIRT1 helps cancer cells survive chemotherapy, SIRT2 inhibits cell growth, and SIRT3 controls mitochondrial health, while SIRT4, SIRT5, SIRT6, and SIRT7 each influence metabolism, angiogenesis, and metastasis. This review explores how these sirtuins contribute to cancer development and highlights their potential as therapeutic targets. By specifically targeting sirtuin activity, new treatments could disrupt PDAC's survival mechanisms, improve drug responses, and potentially offer more effective options for patients with this challenging cancer. Pancreatic ductal adenocarcinoma (PDAC) stands as one of the most lethal cancers, marked by rapid progression, pronounced chemoresistance, and a complex network of genetic and epigenetic dysregulation. Within this challenging context, sirtuins, NAD+-dependent deacetylases, have emerged as pivotal modulators of key cellular processes that drive pancreatic cancer progression. Each sirtuin contributes uniquely to PDAC pathogenesis. SIRT1 influences apoptosis and chemoresistance through hypoxia, enhancing glycolytic metabolism and HIF-1α signaling, which sustain tumor survival against drugs like gemcitabine. SIRT2, conversely, disrupts cancer cell proliferation by inhibiting eIF5A, while SIRT3 exerts tumor-suppressive effects by regulating mitochondrial ROS and glycolysis. SIRT4 inhibits aerobic glycolysis, and its therapeutic upregulation has shown promise in curbing PDAC progression. Furthermore, SIRT5 modulates glutamine and glutathione metabolism, offering an avenue to disrupt PDAC's metabolic dependencies. SIRT6 and SIRT7, through their roles in angiogenesis, EMT, and metastasis, represent additional targets, with modulators of SIRT6, such as JYQ-42, showing potential to reduce tumor invasiveness. This review aims to provide a comprehensive exploration of the emerging roles of sirtuins, a family of NAD+-dependent enzymes, as critical regulators within the oncogenic landscape of pancreatic cancer. This review meticulously explores the nuanced involvement of sirtuins in pancreatic cancer, elucidating their contributions to tumorigenesis and suppression through mechanisms such as metabolic reprogramming, the maintenance of genomic integrity and epigenetic modulation. Furthermore, it emphasizes the urgent need for the development of targeted therapeutic interventions aimed at precisely modulating sirtuin activity, thereby enhancing therapeutic efficacy and optimizing patient outcomes in the context of pancreatic malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Hepcidin is a peptide hormone classically known as a regulator of iron balance. Hepcidin is mainly produced in the liver, but recent studies have shown that hepcidin expression is up-regulated in many cancers, including advanced stages of colorectal cancer (CRC), one of the most frequent neoplasms and a major cause of cancer death worldwide. Accumulating evidence suggests that hepcidin controls multiple steps that sustain CRC cell growth, survival, and diffusion. Hence, the inhibition of CRC-derived hepcidin helps attenuate CRC progression. In this review article, we review the data supporting the regulatory effects of hepcidin on colon tumorigenesis and discuss the potential impact of hepcidin inhibition on the evolutive phases of CRC. Colorectal cancer (CRC) is one of the most frequent neoplasms and a major cause of cancer death worldwide. Despite recent advances in treatment approaches, the prognosis of advanced CRC remains poor, thus indicating the necessity of more effective treatments for CRC patients. CRC cells produce high levels of hepcidin, a peptide hormone that binds to the membrane-bound ferroportin and promotes its internalization and degradation, thus sequestering iron into the cancer cells with the downstream effect of enhancing tumor growth. Additionally, CRC cell-expressed hepcidin prolongs cell survival and, by targeting both CD8+ T cells and myeloid cells, restrains the induction of an efficient immune response against tumor antigens. The greatest expression of hepcidin is found in patients with metastatic CRC, and CRC patients with high hepcidin content have a worse survival rate than those with low hepcidin content. In the present article, we review the data supporting the prominent role of hepcidin in colon tumorigenesis and discuss how hepcidin inhibitors can help treat CRC patients in the metastatic setting with particular regard to the impact of hepcidin modulation on immunotherapeutic outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastasis, the growth of secondary tumors at distant sites, is responsible for the majority of cancer-related deaths. Most of the metastasis growth appears at the same time as the primary tumor or some years after treatment. Nevertheless, very late metastasis can develop, sometimes more than a decade after the end of treatment. At the origin of this late metastasis are isolated dormant tumor cells in the targeted secondary organ. The extracellular matrix of the metastasis-targeted organ plays an important role in maintaining tumor cells in dormancy or in reactivating tumor cell growth. Metastasis is the main cause of cancer-related deaths. The formation and growth of metastasis is a multistep process. Tumor cells extravasating in the secondary organ are in contact with a new microenvironment and a new extracellular matrix (ECM), called the metastatic niche. Some components of the ECM, such as periostin, can induce tumor cell growth in macrometastasis. In contrast, other components, such as Thrombospondin 1 (TSP-1), can maintain isolated cells in a dormant state. During dormancy, intracellular signaling activation, such as p38, maintains tumor cells arrested in the cell-cycle G0 phase for years. At any moment, stress can induce ECM modifications and binding to their specific receptors (mainly integrins) and reactivate dormant tumor cell growth in macrometastasis. In this review, we describe the tumor microenvironment of the different niches implicated in tumor cell dormancy. The role of ECM components and their associated receptors and intracellular signaling in the reactivation of dormant tumor cells in macrometastasis will be emphasized. We also present the different methodologies and experimental approaches used to study tumor cell dormancy. Finally, we discuss the current and future treatment strategies to avoid late metastasis relapse in patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Sex steroid hormones, including estrogens and androgens, are synthesized locally in breast cancer tissue. The estrogen/estrogen receptor (ER) signaling pathway serves as a major therapeutic target for endocrine therapy in ER-positive breast cancer; however, resistance to these therapies poses significant challenges. The androgen receptor (AR) is also highly expressed in breast cancer cells, and intratumoral androgens are implicated in tumor progression and resistance to endocrine therapy. The tumor microenvironment comprises not only tumor cells but also various stromal cells, which play a critical role in tumor development. Estrogen and androgen signaling influence the tumor microenvironment, and variations in hormone receptor expression in breast cancer lead to stromal cell diversity. This review focuses on the roles of ER and AR signaling in both breast cancer cells and stromal cells, summarizing recent findings regarding the effects of estrogens and androgens on stromal cells within the breast cancer microenvironment. Breast cancer is a prevalent hormone-dependent malignancy, and estrogens/estrogen receptor (ER) signaling are pivotal therapeutic targets in ER-positive breast cancers, where endocrine therapy has significantly improved treatment efficacy. However, the emergence of both de novo and acquired resistance to these therapies continues to pose challenges. Additionally, androgens are produced locally in breast carcinoma tissues by androgen-producing enzymes, and the androgen receptor (AR) is commonly expressed in breast cancer cells. Intratumoral androgens play a significant role in breast cancer progression and are closely linked to resistance to endocrine treatments. The tumor microenvironment, consisting of tumor cells, immune cells, fibroblasts, extracellular matrix, and blood vessels, is crucial for tumor progression. Stromal cells influence tumor progression through direct interactions with cancer cells, the secretion of soluble factors, and modulation of tumor immunity. Estrogen and androgen signaling in breast cancer cells affects the tumor microenvironment, and the expression of hormone receptors correlates with the diversity of the stromal cell profile. Notably, various stromal cells also express ER or AR, which impacts breast cancer development. This review describes how sex steroid hormones, particularly estrogens and androgens, affect stromal cells in the breast cancer microenvironment. We summarize recent findings focusing on the effects of ER/AR signaling in breast cancer cells on stromal cells, as well as the direct effects of ER/AR signaling in stromal cells. [ABSTRACT FROM AUTHOR]

Simple Summary: Children with aggressive acute lymphoblastic leukemia (ALL) currently undergo frequent, invasive bone marrow biopsies to monitor their treatment response. This research explores a less invasive alternative using circulating tumor DNA (ctDNA) in blood plasma. We used a mouse model of ALL to study how ctDNA levels change during leukemia progression and treatment. Our findings show that ctDNA can accurately reflect the spread of leukemia and may be better at detecting the presence of residual cancer cells in organs compared to traditional blood tests. This research could lead to less invasive and more effective ways of monitoring treatment response in young leukemia patients, potentially improving their care and outcomes. Background: In infant KMT2A (MLL1)-rearranged (MLL-r) acute lymphoblastic leukemia (ALL), early relapse and treatment response are currently monitored through invasive repeated bone marrow (BM) biopsies. Circulating tumor DNA (ctDNA) in peripheral blood (PB) provides a minimally invasive alternative, allowing for more frequent disease monitoring. However, a poor understanding of ctDNA dynamics has hampered its clinical translation. We explored the predictive value of ctDNA for detecting minimal/measurable residual disease (MRD) and drug response in a patient-derived xenograft (PDX) model of infant MLL-r ALL. Methods: Immune-deficient mice engrafted with three MLL-r ALL PDXs were monitored for ctDNA levels before and after treatment with the menin inhibitor SNDX-50469. Results: The amount of ctDNA detected strongly correlated with leukemia burden during initial engraftment prior to drug treatment. However, following SNDX-50469 treatment, the leukemic burden assessed by either PB leukemia cells through flow cytometry or ctDNA levels through droplet digital polymerase chain reaction (ddPCR) was discrepant. This divergence could be attributed to the persistence of leukemia cells in the spleen and BM, highlighting the ability of ctDNA to reflect disease dynamics in key leukemia infiltration sites. Conclusions: Notably, ctDNA analysis proved to be a superior predictor of MRD compared to PB assessment alone, especially in instances of low disease burden. These findings highlight the potential of ctDNA as a sensitive biomarker for monitoring treatment response and detecting MRD in infant MLL-r ALL. [ABSTRACT FROM AUTHOR]

Simple Summary: Female astronauts on deep-space missions are at increased risk of breast cancer due to exposure to galactic cosmic radiation (GCR). This study aimed to understand how GCR might lead to breast cancer by focusing on a hormone-related pathway involving estrogen receptor alpha (ERα) and other related molecules (ERRα and SPP1). In mice exposed to simulated GCR, we observed increased levels of estrogen, changes in breast tissue growth, and activation of genes that promote tumor formation. Similar results were found when analyzing human breast cancer tissues, suggesting that this pathway is also important in human breast cancer. These findings highlight the ERα-ERRα-SPP1 pathway as a key player in radiation-induced breast cancer risk, providing a potential target for developing protective therapies to safeguard female astronauts during deep-space missions. Background: Exposure to galactic cosmic radiation (GCR) is a breast cancer risk factor for female astronauts on deep-space missions. However, the specific signaling mechanisms driving GCR-induced breast cancer have not yet been determined. Methods: This study aimed to investigate the role of the estrogen-induced ERα-ERRα-SPP1 signaling axis in relation to mammary tumorigenesis in female ApcMin/+ mice exposed to simulated GCR (GCRsim) at 100–110 days post-exposure. Results: In GCRsim-exposed mice, we observed marked elevations in serum estradiol, increased ductal overgrowth, ERα activation, and upregulation of ERα target genes with pro-tumorigenic functions in mammary tissues that was coupled with a higher mammary tumorigenesis, relative to control. Additionally, the ERα target gene Esrra, which encodes ERRα, was also upregulated along with its oncogenic target gene Spp1, indicating the activation of the ERα-ERRα-SPP1 axis in mouse mammary tissues after GCRsim exposure. Using a human tissue microarray and human breast cancer gene expression analysis, we also highlighted the conserved nature of the ERα-ERRα-SPP1 signaling in human breast cancer development. Conclusions: We identified the ERα-ERRα-SPP1 signaling axis as a potential key mediator in GCR-induced breast cancer with conserved activation in human breast cancer. These findings suggest that targeting this pathway could serve as a potential target for therapeutic intervention to safeguard female astronauts during and after a prolonged outer space mission. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases and cancer represent the largest disease burden worldwide. Previously, these two conditions were considered independent, except in terms of cardiotoxicity, which links cancer treatment to subsequent cardiovascular issues. However, recent studies suggest that there are further connections between cancer and heart disease beyond cardiotoxicity. It has been revealed that myocardial dysfunction may promote carcinogenesis, indicating that additional common pathophysiological mechanisms might be involved in the relationship between cardiology and oncology, rather than simply a connection through cardiotoxic effects. These mechanisms may include shared risk factors and common molecular pathways, such as persistent inflammation and neurohormonal activation. This review explores the connection between myocardial dysfunction and cancer, emphasizing their shared risk factors, similar biological mechanisms, and causative factors like cardiotoxicity, along with their clinical implications. [ABSTRACT FROM AUTHOR]

MicroRNAs (miRNAs) are small non-coding RNAs (ncRNAs) that negatively regulate gene expression. MiRNAs regulate fundamental biological processes and have significant roles in several pathologies, including cancer. Cervical cancer is the best-known example of a widespread human malignancy with a demonstrated viral etiology. Infection with high-risk human papillomavirus (hrHPV) has been shown to be a causative factor for cervical carcinogenesis. Despite the occurrence of prophylactic vaccines, highly sensitive HPV diagnostics, and innovative new therapies, cervical cancer remains a main cause of death in developing countries. The relationship between hrHPV infection and cervical cancer depends on the integration of viral DNA to the host genome, disrupting the viral regulator E2 and the continuous production of the viral E6 and E7 proteins, which are necessary to acquire and maintain a transformed phenotype but insufficient for malignant cervical carcinogenesis. Lately, miRNAs, the tumor microenvironment, and immune evasion have been found to be major players in cervical carcinogenesis after hrHPV infection. Many miRNAs have been widely reported as deregulated in cervical cancer. Here, the relevance of miRNA in HPV-mediated transformation is critically reviewed in the context of the natural history of hrHPV infection and cervical cancer. [ABSTRACT FROM AUTHOR]

Cancer cell dormancy is a critical phase in cancer development, wherein cancer cells exist in a latent state marked by temporary but reversible growth arrest. This dormancy phase contributes to anticancer drug resistance, cancer recurrence, and metastasis. Treatment strategies aimed at cancer dormancy can be categorized into two contradictory approaches: inducing cancer cells into a dormant state or eliminating dormant cells. While the former seeks to establish permanent dormancy, the latter aims at eradicating this small population of dormant cells. In this review, we explore the current advancements in therapeutic methods targeting cancer cell dormancy and discuss future strategies. The concept of cancer cell dormancy has emerged as a promising avenue for novel cancer treatments, holding the potential for breakthroughs in the future. [ABSTRACT FROM AUTHOR]

High-grade serous ovarian cancer (HGSOC) remains the most lethal gynecological malignancy, and there is still an unmet medical need to deepen basic research on its origins and mechanisms of progression. Patient-derived organoids of high-grade serous ovarian cancer (HGSOC-PDO) are a powerful model to study the complexity of ovarian cancer as they maintain, in vitro, the mutational profile and cellular architecture of the cancer tissue. Genetic modifications by lentiviral transduction allow novel insights into signaling pathways and the potential identification of biomarkers regarding the evolution of drug resistance. Here, we provide an in-depth and detailed protocol to successfully modify the gene expression of HGSOC-PDOs by lentiviral transduction. As an example, we validate our protocol and create a stable knockdown of the MACC1 oncogene with an efficacy of ≥72% in two HGSOC-PDO lines, which remained stable for >3 months in culture. Moreover, we explain step-by-step the sample preparation for the validation procedures on transcriptional (qPCR) and protein (Western Blot) levels. Sustained downregulation of specific genes by lentiviral transduction enables the analysis of the resulting phenotypic and morphological changes. It serves as a valuable in-vitro model to study the mechanisms of ovarian cancer pathogenesis and allows for the evaluation of therapeutic approaches. [ABSTRACT FROM AUTHOR]

Papillomaviruses (PVs) frequently infect humans as well as non-human species. While most PV infections are asymptomatic, PVs can also cause hyperplastic papillomas (warts) as well as pre-neoplastic and neoplastic lesions. In this review, the life cycle of PVs is discussed, along with the mechanisms by which PVs cause hyperplastic and neoplastic diseases. The humoral and cell-mediated immune responses to PVs are reviewed, giving context to the later discussion on the use of vaccines to reduce canine and feline PV-associated disease. Both dogs and cats are infected by numerous different PV types classified into multiple different PV genera. The taxonomic classification of PVs is reviewed, along with the significance of this classification. The PV-associated diseases of dogs and cats are then described. These descriptions include the clinical presentation of the disease, the causative PV types, the histological features that allow diagnosis, and, where appropriate, possible treatment options. The review is comprehensive and contains the latest information about PVs and the diseases they cause in dogs and cats. [ABSTRACT FROM AUTHOR]

Tumor vaccine is a promising immunotherapy for solid tumors. Therapeutic tumor vaccines aim at inducing tumor regression, establishing durable antitumor memory, and avoiding non-specific or adverse reactions. However, tumor-induced immune suppression and immune resistance pose challenges to achieving this goal. In this article, we review multiple challenges currently faced in the development of therapeutic tumor vaccines, with a particular focus on anonymous antigen vaccines in situ as a new direction. We summarize the research progress in this area, aiming to provide a reference for future studies on tumor vaccines. [ABSTRACT FROM AUTHOR]

Background: Intraductal papillary mucinous neoplasms (IPMNs) display four histological subtypes: gastric foveolar, pancreaticobiliary, intestinal, and oncocytic. All of these subtypes harbor a different risk of cancer development. The clinical impact of these subtypes concerning the occurrence of high-grade dysplasia (HGD)/cancer (C) in specific morphological types, such as branch-duct (BD), main-duct (MD), and mixed-type (MT) IPMNs, has been less investigated. Hence, our aim was to investigate the prevalence of histological subtypes and their possible association with HGD/C concerning morphologically different IPMNs. Methods: This was a retrospective review of demographics, risk factors, and histological features in a surgical cohort of patients having undergone resection for suspect malignant IPMNs at a high-volume tertiary center from 2007 to 2017. Results: A total of 273 patients were resected for IPMNs from during the study period, of which 188 were included in the final analysis. With sex- and age-adjusted multivariable logistic regression analysis across the entire cohort, gastric foveolar subtypes were associated with a reduced prevalence of HGD/C (OR = 0.30; 0.11–0.81, 95% CI, 95%CI; p = 0.01). With univariable logistic regression analysis, in the BD-IPMN subgroup, the pancreaticobiliary subtype was associated with an increased prevalence of HGD/C (OR = 18.50, 1.03–329.65, 95% CI; p = 0.04). In MD- and MT-IPMNs, the gastric foveolar subtype was associated with a decreased prevalence of HGD/cancer (OR = 0.30, 0.13–0.69, 95% CI; p = 0.004). Conclusions: In MD and MT-IPMNs, the gastric-foveolar subtype is associated with a lower prevalence of HGD/C, possibly identifying in such a high-risk group, a subgroup with more indolent behavior. In BD-IPMNs, the pancreaticobiliary subtype is associated with a higher prevalence of HGD/C, conversely identifying among those patients, a subgroup deserving special attention. [ABSTRACT FROM AUTHOR]

Simple Summary: FOXM1 is a pro-oncogenic transcription factor that is often upregulated in triple-negative breast cancer and aggressive solid cancers. FOXM1 drives cell proliferation, invasion, metastasis, drug resistance, and tumor growth and progression, and its expression is associated with poor prognosis and shorter patient survival. Therefore, FOXM1 is considered as an emerging therapeutic target. This review highlights the role of FOXM1, the mechanisms regulating its expression, its potential as a novel molecular target in TNBC and solid tumors, and attempts to develop FOXM1 inhibitors. Triple-negative breast cancer (TNBC) is one of the most aggressive forms of breast cancer, lacking common treatment targets such as estrogen (ER), progesterone (PR), and HER2 receptors. This subtype is associated with significant heterogeneity, chemoresistance, early recurrence, metastasis, and poor patient survival. FOXM1 is a cancer-promoting transcription factor that plays a critical role in TNBC and other highly aggressive cancers by driving cell proliferation, invasion, metastasis, and drug resistance. In TNBC, mutations in the TP53 gene—detected in approximately 80% of patients—lead to the overexpression of FOXM1, making it a promising therapeutic target. Beyond TNBC, FOXM1 is implicated in other solid cancers, such as brain (glioblastoma), lung, and pancreatic cancers, and is considered an Achilles' heel of aggressive cancers. Despite its potential as a therapeutic target, there are currently no FDA-approved FOXM1 inhibitors, and none have advanced to clinical trials. This review explores the role of FOXM1 in cancer progression and highlights the current status of efforts to develop effective FOXM1 inhibitors. [ABSTRACT FROM AUTHOR]

Simple Summary: Upper tract urothelial carcinoma (UTUC) is a rare but aggressive cancer that is difficult to predict and treat effectively. Current methods for assessing a patient's outlook often fall short. Our research introduces a new approach that could change this. We look at the fat surrounding the kidney using detailed CT scan analysis, combined with standard clinical information. This method provides a more accurate prediction of how patients with UTUC might fare. By examining the texture and patterns in this fat tissue, we can potentially detect early signs of cancer spread that are not visible to the naked eye. Our findings could help doctors make better treatment decisions, such as whether to use chemotherapy before surgery or how extensive the surgery should be. This personalized approach aims to improve outcomes for patients with this challenging cancer. Background: Upper tract urothelial carcinoma (UTUC) presents significant challenges in prognostication due to its rarity and complex anatomy. This study introduces a novel approach integrating perirenal fat (PRF) radiomics with clinical factors to enhance prognostic accuracy in UTUC. Methods: The study retrospectively analyzed 103 UTUC patients who underwent radical nephroureterectomy. PRF radiomics features were extracted from preoperative CT scans using a semi-automated segmentation method. Three prognostic models were developed: clinical, radiomics, and combined. Model performance was assessed using concordance index (C-index), time-dependent Area Under the Curve (AUC), and integrated Brier score. Results: The combined model demonstrated superior performance (C-index: 0.784, 95% CI: 0.707–0.861) compared to the radiomics (0.759, 95% CI: 0.678–0.840) and clinical (0.653, 95% CI: 0.547–0.759) models. Time-dependent AUC analysis revealed the radiomics model's particular strength in short-term prognosis (12-month AUC: 0.9281), while the combined model excelled in long-term predictions (60-month AUC: 0.8403). Key PRF radiomics features showed stronger prognostic value than traditional clinical factors. Conclusions: Integration of PRF radiomics with clinical data significantly improves prognostic accuracy in UTUC. This approach offers a more nuanced analysis of the tumor microenvironment, potentially capturing early signs of tumor invasion not visible through conventional imaging. The semi-automated PRF segmentation method presents advantages in reproducibility and ease of use, facilitating potential clinical implementation. [ABSTRACT FROM AUTHOR]

Understanding the regulation of somatic stem cells, both during homeostasis and in response to environmental challenges like injury, infection, chemical exposure, and nutritional changes, is critical because their dysregulation can result in tissue degeneration or tumorigenesis. The use of models such as the Drosophila and mammalian adult intestines offers valuable insights into tissue homeostasis and regeneration, advancing our knowledge of stem cell biology and cancer development. This review highlights significant findings from recent studies, unveiling the molecular mechanisms that govern self-renewal, proliferation, differentiation, and regeneration of intestinal stem cells (ISCs). These insights not only enhance our understanding of normal tissue maintenance but also provide critical perspectives on how ISC dysfunction can lead to pathological conditions such as colorectal cancer (CRC). [ABSTRACT FROM AUTHOR]

Simple Summary: This research explores the impact of modern lifestyle factors, such as exposure to artificial light, shift work, and dietary habits, on our body's internal clock and its association with increased body fat deposits and cancer risk. By reviewing various published studies, we aim to understand the physiological mechanisms underlying the increased risk of cancer associated with an unhealthy lifestyle. In particular, there is evidence that disruptions in the body's natural rhythms can lead to abnormal cortisol levels, which in turn may promote fat buildup and create an adipose environment favorable for cancer growth. Additionally, we explore the anticancer effects of melatonin, either directly on cancer cells or through its role in preventing the formation of an adipose microenvironment conducive to tumor development. Our findings could offer new insights into how lifestyle choices and melatonin regulation influence cancer development, helping researchers and healthcare professionals better understand and address these risks. Background: Recent research underscores a crucial connection between circadian rhythm disruption and cancer promotion, highlighting an urgent need for attention. Objectives: Explore the molecular mechanisms by which modern lifestyle factors—such as artificial light exposure, shift work, and dietary patterns—affect cortisol/melatonin regulation and cancer risk. Methods: Employing a narrative review approach, we synthesized findings from Scopus, Google Scholar, and PubMed to analyze lifestyle impacts on circadian health, focusing on cortisol and melatonin chronobiology as molecular markers. We included studies that documented quantitative changes in these markers due to modern lifestyle habits, excluding those lacking quantitative data or presenting inconclusive results. Subsequent sections focused solely on articles that quantified the effects of circadian disruption on adipogenesis and tumor microenvironment modifications. Results: This review shows how modern habits lead to molecular changes in cortisol and melatonin, creating adipose microenvironments that support cancer development. These disruptions facilitate immune evasion, chemotherapy resistance, and tumor growth, highlighting the critical roles of cortisol dysregulation and melatonin imbalance. Conclusions: Through the presented findings, we establish a causal link between circadian rhythm dysregulation and the promotion of certain cancer types. By elucidating this relationship, the study emphasizes the importance of addressing lifestyle factors that contribute to circadian misalignment, suggesting that targeted interventions could play a crucial role in mitigating cancer risk and improving overall health outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This study investigates the critical yet understudied role of miRNAs in areca nut-induced carcinogenesis in head and neck cancer (HNC). Through comprehensive profiling, we identified 84 miRNAs, comprising 39 oncogenic miRNAs (OncomiRs) and 45 tumor-suppressive miRNAs (TsmiRs) associated with areca nut-induced HNC. Further analysis of the oncogenic mechanisms revealed that 740 genes are cross-regulated by a cluster of eight hub TsmiRs. These areca nut-modulated miRNAs significantly impact key cancer-related pathways, including p53, PI3K-AKT, MAPK, and Ras signaling, and regulate critical oncogenic processes related to cell motility and survival. Moreover, miR-499a-5p was validated as a vital regulator, which mitigated areca nut-induced cancer progression, including cell migration, invasion, and chemoresistance. Our findings highlight the potential of this miRNA panel for clinical applications in risk assessment, diagnosis, and prognosis of areca nut-associated malignancies, opening new avenues for future research and clinical practice. Background: While miRNAs are increasingly recognized for their role in tumorigenesis, their involvement in head and neck cancer (HNC) remains insufficiently explored. Additionally, the carcinogenic mechanisms of areca nut, a major habitual carcinogen in Southeast Asia, are not well understood. Methods and results: This study adopts a systematic approach to identify miRNA profiles associated with areca nut-induced HNC. Using miRNA microarray analysis, we identified 292 miRNAs dysregulated in areca nut-treated HNC cells, with 136 upregulated and 156 downregulated. Bioinformatic analysis of the TCGA-HNSC dataset uncovered a set of 692 miRNAs relevant to HNC development, comprising 449 overexpressed and 243 underexpressed in tumor tissues. Integrating these datasets, we defined a signature of 84 miRNAs, including 39 oncogenic miRNAs (OncomiRs) and 45 tumor-suppressive miRNAs (TsmiRs), highlighting their pivotal role in areca nut-induced carcinogenesis. MultiMiR analysis identified 740 genes cross-regulated by eight hub TsmiRs, significantly impacting key cancer-related pathways (p53, PI3K-AKT, MAPK, and Ras) and critical oncogenic processes. Moreover, we validated miR-499a-5p as a vital regulator, demonstrating its ability to mitigate areca nut-induced cancer progression by reducing cell migration, invasion, and chemoresistance. Conclusions: Thus, this miRNA signature addresses a crucial gap in understanding the molecular underpinnings of areca nut-induced carcinogenesis and offers a promising platform for clinical applications in risk assessment, diagnosis, and prognosis of areca nut-associated malignancies. [ABSTRACT FROM AUTHOR]

Simple Summary: Environmental pollution caused by nano- and microplastics (MPs) is widespread and has become a global issue. There is a confirmed accumulation of MPs in animal and human tissues, raising concerns about potential health effects. The accumulation of NMPs in human tissues, as well as their genotoxicity, mutagenicity, and impact on cancer development, is a relatively new area of research that presents several challenges, mainly related to instrumental limitations and ensuring quality assurance and quality control (QA/QC) in studies of both exposure and subsequent fate in the body, such as translocation and possible accumulation. Background: Humans cannot avoid plastic exposure due to its ubiquitous presence in the natural environment. The waste generated is poorly biodegradable and exists in the form of MPs, which can enter the human body primarily through the digestive tract, respiratory tract, or damaged skin and accumulate in various tissues by crossing biological membrane barriers. There is an increasing amount of research on the health effects of MPs. Most literature reports focus on the impact of plastics on the respiratory, digestive, reproductive, hormonal, nervous, and immune systems, as well as the metabolic effects of MPs accumulation leading to epidemics of obesity, diabetes, hypertension, and non-alcoholic fatty liver disease. MPs, as xenobiotics, undergo ADMET processes in the body, i.e., absorption, distribution, metabolism, and excretion, which are not fully understood. Of particular concern are the carcinogenic chemicals added to plastics during manufacturing or adsorbed from the environment, such as chlorinated paraffins, phthalates, phenols, and bisphenols, which can be released when absorbed by the body. The continuous increase in NMP exposure has accelerated during the SARS-CoV-2 pandemic when there was a need to use single-use plastic products in daily life. Therefore, there is an urgent need to diagnose problems related to the health effects of MP exposure and detection. Methods: We collected eligible publications mainly from PubMed published between 2017 and 2024. Results: In this review, we summarize the current knowledge on potential sources and routes of exposure, translocation pathways, identification methods, and carcinogenic potential confirmed by in vitro and in vivo studies. Additionally, we discuss the limitations of studies such as contamination during sample preparation and instrumental limitations constraints affecting imaging quality and MPs detection sensitivity. Conclusions: The assessment of MP content in samples should be performed according to the appropriate procedure and analytical technique to ensure Quality and Control (QA/QC). It was confirmed that MPs can be absorbed and accumulated in distant tissues, leading to an inflammatory response and initiation of signaling pathways responsible for malignant transformation. [ABSTRACT FROM AUTHOR]

Simple Summary: Kaposi sarcoma-associated herpesvirus (KSHV) is associated with lymphoproliferative disorders, including primary effusion lymphoma and multicentric Castleman disease. KSHV expresses viral proteins that aid in the evasion of antiviral immune responses and manipulate host factors and signaling to promote cell survival. By altering the cell environment, KSHV contributes to lymphomagenesis. Approximately 15–20% of cancers are caused by viruses. Kaposi sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus 8 (HHV8), is an oncogenic virus that is the etiologic agent of not only Kaposi sarcoma but also the lymphoproliferative disorders, primary effusion lymphoma (PEL) and multicentric Castleman disease (MCD). KSHV can infect a broad tropism of cells, including B lymphocytes, wherein KSHV encodes specific viral proteins that can transform the cell. KSHV infection precedes the progression of PEL and MCD. KSHV establishes lifelong infection and has two phases of its lifecycle: latent and lytic. During the latent phase, viral genomes are maintained episomally with limited gene expression. Upon sporadic reactivation, the virus enters its replicative lytic phase to produce infectious virions. KSHV relies on its viral products to modulate host factors to evade immune detection or to co-opt their function for KSHV persistence. These manipulations dysregulate normal cell pathways to ensure cell survival and inhibit antiviral immune responses, which in turn, contribute to KSHV-associated malignancies. Here, we highlight the known molecular mechanisms of KSHV that promote lymphomagenesis and how these findings identify potential therapeutic targets for KSHV-associated lymphomas. [ABSTRACT FROM AUTHOR]

Simple Summary: Mucosal melanoma is a rare and aggressive form of melanoma that is different from the more common skin melanoma. Unfortunately, current treatments have not significantly improved outcomes for patients with this disease. Our research focuses on understanding the biological mechanisms that drive mucosal melanoma and finding new treatment strategies. We discovered that the enhancer of zeste homolog 2 (EZH2) plays a crucial role in promoting the growth of mucosal melanoma cells and contributes to their resistance to a type of cell death known as ferroptosis. By inhibiting EZH2 and combining this with drugs that induce ferroptosis, we were able to effectively slow tumor growth. Our findings suggest that targeting the EZH2 pathway could offer a new therapeutic approach to treating mucosal melanoma, potentially improving patient outcomes. Background: Mucosal melanoma (MM) is epidemiologically, biologically, and molecularly distinct from cutaneous melanoma. Current treatment strategies have failed to significantly improve the prognosis for MM patients. This study aims to identify therapeutic targets and develop combination strategies by investigating the mechanisms underlying the tumorigenesis and progression of MM. Methods: We analyzed the copy number amplification of enhancer of zeste homolog 2 (EZH2) in 547 melanoma patients and investigated its correlation with clinical prognosis. Utilizing cell lines, organoids, and patient-derived xenograft models, we assessed the impact of EZH2 on cell proliferation and sensitivity to ferroptosis. Further, we explored the mechanisms of ferroptosis resistance associated with EZH2 by conducting RNA sequencing and chromatin immunoprecipitation sequencing. Results: EZH2 copy number amplification was closely associated with malignant phenotype and poor prognosis in MM patients. EZH2 was essential for MM cell proliferation in vitro and in vivo. Moreover, genetic perturbation of EZH2 rendered MM cells sensitized to ferroptosis. Combination treatment of EZH2 inhibitor with ferroptosis inducer significantly inhibited the growth of MM. Mechanistically, EZH2 inhibited the expression of Krüpple-Like factor 14 (KLF14), which binds to the promoter of solute carrier family 7 member 11 (SLC7A11) to repress its transcription. Loss of EZH2 therefore reduced the expression of SLC7A11, leading to reduced intracellular SLC7A11-dependent glutathione synthesis to promote ferroptosis. Conclusion: Our findings not only establish EZH2 as a biomarker for MM prognosis but also highlight the EZH2-KLF14-SLC7A11 axis as a potential target for MM treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: A pseudogene, by definition, is a segment of DNA that structurally resembles an established gene but has undergone mutation drift or genomic translocation where it no longer codes for an active protein. An example of this type of relationship is seen with the oncofetal protein Cripto-1 (CR1) and its pseudogene homolog Cripto-3 (CR3). The CR1 gene is expressed on chromosome 3 and CR3 on the X chromosome. They both code for a 188AA protein but differ by six AAs. Given the closeness of their protein structure, commercially available antibodies cannot differentiate CR1 from CR3. Hence, CR3 remains a pseudogene in human biology and its relationship with tumor malignancies underdetermined. Our newly generated discriminatory anti-CR1/anti-CR3 monoclonal antibodies have now proven that CR3 is a translated protein found in diverse human cancers, tracking with disease severity, involved with cell signaling and expressed as a cell-tethered or soluble entity, thus negating its pseudogene status. Background/Objectives: Cripto-1 (CR1) is a plurifunctional embryonic protein required for implantation and re-expressed in the adult during wound repair, inflammation, and tumorigenesis. CR1 and its predicted CR1 pseudogene product Cripto-3/CR3 are highly homologous proteins, and given this physical attribute, commercially available antibodies cannot discriminate between CR1 and CR3. Methods: A series of mouse monoclonal antibodies [MoAbs] were developed with a high-affinity binding that can differentiate human CR1/CR3 proteins and showed no measurable cross-reactivity. Results: Using these reagents, we confirm that CR3 is a bona fide translated protein found in human tumor tissue, cancer cell lysates, and in normal/cancer patient donor sera. We also reveal that CR1 and CR3 compete for binding to signal transduction protein Nodal, glucose-regulated protein 78Da (GRP78), and activin receptor-like kinase 4 (Alk4). Our discriminatory MoAbs provide new reagents to help clarify current CR1/CR3 protein expression vagaries in the Cripto field of study, challenging established CR1 conventions. In addition, our data validate CR3 involvement in human carcinogenesis and cell signaling pathways, with potential clinical relevance in determining cancer patient prognosis and disease severity. [ABSTRACT FROM AUTHOR]

Since Epstein–Barr Virus (EBV) was isolated 60 years ago, it has been studied clinically, epidemiologically, immunologically, and molecularly in the ensuing years. These combined studies allow a broad mechanistic understanding of how this ubiquitous human pathogen which infects more than 90% of adults can rarely cause multiple types of lymphomas. We survey these findings to provide a coherent description of its oncogenesis. [ABSTRACT FROM AUTHOR]

The host transcription factor p53 is a critical tumor suppressor in HPV-induced carcinogenesis, regulating target genes involved in cell cycle arrest and apoptosis. However, the p53 targets have not been thoroughly analyzed in HPV-infected cells. In this study, p53 signaling in HPV16 and HPV18 cells was activated by depleting the viral oncoprotein E6. Subsequently, p53-regulated genes were identified by comparing them with genes altered in p53-silenced cells. True p53 targets were defined as genes with at least one overlapping p53 binding site and ChIP peak near their locus. Our analysis revealed that while some p53 targets were common to both the HPV16 and HPV18 cells, the majority of the targets differed between these two types, potentially contributing to the varying prevalence of HPV16 and HPV18 in cervical cancer. Additionally, we identified SCN2A as a novel p53 target involved in p53-induced cell cycle arrest in HPV-related carcinogenesis. This study provides new insights into the mechanisms by which p53 inhibits HPV-induced carcinogenesis. [ABSTRACT FROM AUTHOR]

Birds, especially the chick and hen, have been important biomedical research models for centuries due to the accessibility of the avian embryo and the early discovery of avian viruses. Comprehension of avian tumor virology was a milestone in basic cancer research, as was that of non-viral genesis, as it enabled the discovery of oncogenes. Furthermore, studies on avian viruses provided initial insights into Kaposi's sarcoma and EBV-induced diseases. However, the role of birds in human carcinogenesis extends beyond the realm of virology research. Utilization of CAM, the chorioallantoic membrane, an easily accessible extraembryonic tissue with rich vasculature, has enabled studies on tumor-induced angiogenesis and metastasis and the efficient screening of potential anti-cancer compounds. Also, the chick embryo alone is an effective preclinical in vivo patient-derived xenograft model, which is important for the development of personalized therapies. Furthermore, adult birds may also closely resemble human oncogenesis, as evidenced by the laying hen, which is the only animal model of a spontaneous form of ovarian cancer. Avian models may create an interesting alternative compared with mammalian models, enabling the creation of a relatively cost-effective and easy-to-maintain platform to address key questions in cancer biology. [ABSTRACT FROM AUTHOR]

Cancers of the nose, and especially the nose vestibule, represent a significant challenge for clinicians due to their rarity, the intricate nature of surrounding vital structures, the nonspecific early symptoms, and the etiological factors that are not completely understood. Emerging research suggests that alterations in the nasal microbiome, also known as microbial dysbiosis, may contribute to the pathogenesis of those malignancies through mechanisms involving chronic inflammation, immune modulation, and cellular changes. The aims of this paper are to review the current literature covering the nasal microbiome's role in carcinogenesis, particularly in the context of squamous cell carcinoma, and to explore how microbial dysbiosis might foster a pro-tumorigenic environment. It further discusses potential future directions for research and therapeutic approaches. [ABSTRACT FROM AUTHOR]