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The chromatin-associated protein WD Repeat Domain 5 (WDR5) is a promising target for cancer drug discovery, with most efforts blocking an arginine-binding cavity on the protein called the WIN site that tethers WDR5 to chromatin. WIN site inhibitors (WINi) are active against multiple cancer cell types in vitro, the most notable of which are those derived from MLL-rearranged (MLLr) leukemias. Peptidomimetic WINi were originally proposed to inhibit MLLr cells via dysregulation of genes connected to hematopoietic stem cell expansion. Our discovery and interrogation of small-molecule WINi, however, revealed that they act in MLLr cell lines to suppress ribosome protein gene (RPG) transcription, induce nucleolar stress, and activate p53. Because there is no precedent for an anticancer strategy that specifically targets RPG expression, we took an integrated multi-omics approach to further interrogate the mechanism of action of WINi in human MLLr cancer cells. We show that WINi induce depletion of the stock of ribosomes, accompanied by a broad yet modest translational choke and changes in alternative mRNA splicing that inactivate the p53 antagonist MDM4. We also show that WINi are synergistic with agents including venetoclax and BET-bromodomain inhibitors. Together, these studies reinforce the concept that WINi are a novel type of ribosome-directed anticancer therapy and provide a resource to support their clinical implementation in MLLr leukemias and other malignancies.

Glutamine, a multifaceted nonessential/conditionally essential amino acid integral to cellular metabolism and immune function, holds pivotal importance in the landscape of cancer therapy. This review delves into the intricate dynamics surrounding both glutamine antagonism strategies and glutamine supplementation within the context of cancer treatment, emphasizing the critical role of glutamine metabolism in cancer progression and therapy. Glutamine antagonism, aiming to disrupt tumor growth by targeting critical metabolic pathways, is challenged by the adaptive nature of cancer cells and the complex metabolic microenvironment, potentially compromising its therapeutic efficacy. In contrast, glutamine supplementation supports immune function, improves gut integrity, alleviates treatment-related toxicities, and improves patient well-being. Moreover, recent studies highlighted its contributions to epigenetic regulation within cancer cells and its potential to bolster anti-cancer immune functions. However, glutamine implementation necessitates careful consideration of potential interactions with ongoing treatment regimens and the delicate equilibrium between supporting normal cellular function and promoting tumorigenesis. By critically assessing the implications of both glutamine antagonism strategies and glutamine supplementation, this review aims to offer comprehensive insights into potential therapeutic strategies targeting glutamine metabolism for effective cancer management.

As part of a symposium, current and former directors of Immune Monitoring cores and investigative oncologists presented insights into the past, present and future of immune assessment. Dr. Gnjatic presented a classification of immune monitoring technologies ranging from universally applicable to experimental protocols, while emphasizing the need for assay harmonization. Dr. Obeng discussed physiologic differences among CD8 T cells that align with anti-tumor responses. Dr. Lyerly presented the Soldano Ferrone lecture, commemorating the passionate tumor immunologist who inspired many, and covered a timeline of monitoring technology development and its importance to immuno-oncology. Dr. Sonabend presented recent achievements in glioblastoma treatment, accentuating the range of monitoring techniques that allowed him to refine patient selection for clinical trials. Dr. Guevara-Patiño focused on hypoxia within the tumor environment and stressed that T cell viability is not to be confused with functionality. Dr. Butterfield accentuated monitoring of dendritic cell metabolic (dys)function as a determinant for tumor vaccine success. Lectures were interspersed with select abstract presentations. To summarize the concepts, Dr. Maecker from Stanford led an informative forum discussion, pointing towards the future of immune monitoring. Immune monitoring continues to be a guiding light towards effective immunotherapeutic strategies.

Methods for producing drugs directly at the cancer site, particularly using bioorthogonal metal catalysts, are being explored to mitigate the side effects of therapy. Albumin‐based artificial metalloenzymes (ArMs) catalyze reactions in living mice while protecting the catalyst in the hydrophobic pocket. Here, we describe the in situ preparation and application of biocompatible tumor‐targeting ArMs using circulating albumin, which is abundant in the bloodstream. The ArM was formed using blood albumin through the intravenous injection of ruthenium conjugated with an albumin‐binding ligand; the tumor‐targeting unit was conjugated to the ArM using its catalytic activity, and the ArM was transported to the cancer site. The delivered ArM catalyzed a second tagging reaction of the proapoptotic peptide on the cancer surface, successfully suppressing cancer proliferation. This approach, which efficiently leveraged the persisting reactivity twice in vivo, holds promise for future in vivo metal‐catalyzed drug synthesis utilizing endogenous albumin. [ABSTRACT FROM AUTHOR]

In the current preclinical anti-tumor researches, there is a general lack of an in vivo model that can quickly and efficiently screen effective anti-tumor drugs. As a species that is 87% genetically similar to humans, zebrafish have been widely used to model human diseases, and they are considered an alternative economic model for studying cancer development, proliferation, and metastasis. The zebrafish tumor xenograft model has been effectively used for cancer drug development at all levels, including target validation, and high-throughput screening of long non-coding RNAs (lncRNAs) that may be involved in tumor regulation. In this review, we provide a comprehensive overview of zebrafish as an in vivo model for cancer cell growth, migration, anti-tumor immunotherapy, and anti-tumor drug screening. In addition, the regulatory mechanisms of some active lncRNAs have been identified to play a role in the pathogenesis of cancer, but it is still necessary to take advantage of the efficient zebrafish model to screen and learn more about the role of these molecules in tumor development and migration. Current anti-tumor therapies are limited by severe toxicity and multidrug resistance. There is an urgent need for the cost-effective and efficient in vivo research tools to improve our understanding and overcome these problems. This paper reviews the different purposes of anti-tumor research using zebrafish model. We discuss the use of zebrafish in cancer cell proliferation and metastasis, identifying signaling pathways, cancer drug discovery and treatment development, and toxicity studies. Finally, this review highlights the limitations of the field and future directions to effectively utilize zebrafish as a highly efficient model for cancer treatment development. [ABSTRACT FROM AUTHOR]

Background: Traditional chemotherapeutic agents suffer from a lack of selectivity, poor targeting ability, and drug resistance. Developing tumor-specific therapies is crucial for precisely eliminating tumors while circumventing toxicity to normal tissues. Disulfiram (DSF), an FDA-approved drug for treating alcohol dependence, exhibits antitumor effect by forming complexes with copper ions (Cu(DDC)2). Here, we developed a Cu-doped polydopamine-based nanosystem (DSF@CuPDA-PEGM) to achieve in situ generation of toxic Cu(DDC)2. Results: In cancer cells with elevated H2O2 contents, CuPDA responsively degrades to release Cu ions and DSF, allowing on-site synthesis of Cu(DDC)2 with potent antitumor activity. DSF@CuPDA-PEGM exhibits excellent therapeutic efficacy against both drug-sensitive and drug-resistant cancer cells while minimizing toxicity to noncancerous cells. Moreover, DSF@CuPDA-PEGM promotes the immune response by inducing cancer cell immunogenic death, thereby augmenting anti-PD-1-based immune checkpoint blockade therapy. Conclusion: A tumor-specifically degradable Cu-doped polydopamine-based nanosystem is developed to achieve in situ synthesis of antitumor compounds, providing a promising approach to precisely eliminate tumors and heighten chemo-immunotherapy. [ABSTRACT FROM AUTHOR]

Background: Arginase is abundantly expressed in colorectal cancer and disrupts arginine metabolism, promoting the formation of an immunosuppressive tumor microenvironment. This significant factor contributes to the insensitivity of colorectal cancer to immunotherapy. Tumor-associated macrophages (TAMs) are major immune cells in this environment, and aberrant arginine metabolism in tumor tissues induces TAM polarization toward M2-like macrophages. The natural compound piceatannol 3ʹ-O-glucoside inhibits arginase activity and activates nitric oxide synthase, thereby reducing M2-like macrophages while promoting M1-like macrophage polarization. Methods: The natural compounds piceatannol 3ʹ-O-glucoside and indocyanine green were encapsulated within microparticles derived from tumor cells, termed PG/ICG@MPs. The enhanced cancer therapeutic effect of PG/ICG@MP was assessed both in vitro and in vivo. Results: PG/ICG@MP precisely targets the tumor site, with piceatannol 3ʹ-O-glucoside concurrently inhibiting arginase activity and activating nitric oxide synthase. This process promotes increased endogenous nitric oxide production through arginine metabolism. The combined actions of nitric oxide and piceatannol 3ʹ-O-glucoside facilitate the repolarization of tumor-associated macrophages toward the M1 phenotype. Furthermore, the increase in endogenous nitric oxide levels, in conjunction with the photodynamic effect induced by indocyanine green, increases the quantity of reactive oxygen species. This dual effect not only enhances tumor immunity but also exerts remarkable inhibitory effects on tumors. Conclusion: Our research results demonstrate the excellent tumor-targeting effect of PG/ICG@MPs. By modulating arginine metabolism to improve the tumor immune microenvironment, we provide an effective approach with clinical translational significance for combined cancer therapy. [ABSTRACT FROM AUTHOR]

Exosomes which are membrane vesicles released by cells have gained significant interest in the field of cancer therapy as a novel means of intercellular communication. Their role in immune activation and their pathophysiological functions in cancer therapy have been recognized. Exosomes carry diverse bioactive components including proteins, mRNA, microRNAs, and bioactive lipids. These molecules have therapeutic potential in promoting tissue regeneration, supporting stem cell activity, preventing cell death, modulating immune responses, and promoting the growth of new blood vessels. However, the precise roles of exosomes derived from mesenchymal stem cells (MSCs) in the treatment of various cancers are still not fully understood. Consequently, cancer stem cells (CSCs) can self-renew and differentiate into various cell types. Understanding the mechanisms that sustain their persistence is crucial for developing effective therapies. Exosomes have recently gained interest as vehicles for intercellular communication between CSCs and non-CSCs, influencing cancer progression and the microenvironment. Research is ongoing on the utilization of exosomes derived from cancer stem cells (CSC-Exosome) for cancer treatment. The composition of extracellular vesicles is influenced by the specific type and condition of the cells from which they are secreted. Circulating exosomes contain stable RNA molecules such as mRNAs, microRNAs, and long non-coding RNAs (lncRNAs). In this review, we will explore the significance of exosomes and their diverse cellular combinations in the context of cancer therapy. [ABSTRACT FROM AUTHOR]

Tertiary lymphoid structures (TLSs) are ectopic lymphoid aggregates formed by the structured accumulation of immune cells such as B cells and T cells in non-lymphoid tissues induced by infection, inflammation, and tumors. They play a crucial role in the immune response, particularly in association with tumor development, where they primarily exert anti-tumor immune functions during tumorigenesis. Current research suggests that TLSs inhibit tumor growth by facilitating immune cell infiltration and are correlated with favorable prognosis in various solid tumors, serving as an indicator of immunotherapy effectiveness to some extent. Therefore, TLSs hold great promise as a valuable biomarker. Most importantly, immunotherapies aimed to prompting TLSs formation are anticipated to be potent adjuncts to current cancer treatment. This review focuses on the formation process of TLSs and their potential applications in cancer therapy. [ABSTRACT FROM AUTHOR]

The concomitant activation of both the YAP1 co-transcription factor and RAS GTPases is a hallmark of several aggressive cancers, though the intricacies of their relationship and implications for oncogenesis are still poorly understood. This review has presented a cooperative model where YAP1 and RAS are not independently acting oncogenes but rather interdependently acting ones, with each fulfilling an essential role within the oncogenic process. YAP1 is responsible for initiating the expression of key proteins that contribute to various cancer traits. However, these proteins must often be transported into the cytoplasm to exert their effects. We suggest that oncogenic RAS actually facilitates this transport, enabling the phosphorylation and subsequent activation of the nuclear transporter XPO1 (aka Exportin1). This mechanism is particularly crucial for anti-apoptotic proteins. Instead of being sequestered within the nucleus in an ineffective state, these proteins are rather shuttled into the cytoplasm. Within the cytoplasm, they can effectively inhibit apoptosis, undermining by these means the efficacy of chemotherapeutic agents designed to induce cell death in cancer cells. Therefore, a clearer understanding of the oncogenic partnership between RAS and YAP1 will likely provide new insights into the molecular underpinnings of cancer and highlight as well potential targets for therapeutic interventions designed to disrupt this pernicious interaction. I. YAP1 triggers expression of its target genes, some of which encode cargoes with a nuclear export signal. In response to physiological signals, some cargoes are shuttled into the cytoplasm. Exportin1 serves as the transfer vehicle from the nucleus into the cytoplasm (not shown). For functional nuclear proteins, this shuttling terminates their function, whereas for cytoplasmic proteins, it does initiate their function. In this drawing, the topology within the nucleus is not depicted. II. Oncogenic RAS leads to Exportin1 activation and subsequent unwarranted nuclear-cytoplasmic shuttling of cargoes [17, 35]. The cascade from RAS to Exportin1 is not depicted for the sake of clarity. Some of the cargoes are oncoproteins, cytoplasmic GTPases regulators, or antiapoptotic proteins (example shown: BIRC5 aka Survivin). These latter proteins are now empowered to hinder apoptosis, as expected upon anti-cancer therapies. Of course, the BIRC5 is not the only aberrantly shuttled protein. Another example is Beclin1 (BECN1), which is subjected to the same fate; once in the cytoplasm, it does initiate autophagy in the absence of any autophagic clue [35]. [ABSTRACT FROM AUTHOR]

Cancer, a complex and multifaceted group of diseases, continues to challenge the boundaries of medical science and healthcare. Its relentless impact on global health, both in terms of prevalence and mortality, underscores the urgent need for a comprehensive understanding of its underlying mechanisms and innovative therapeutic approaches. In recent years, significant progress has been achieved in identifying the genetic and epigenetic mechanisms that cause cancer development and treatment resistance. Researchers are currently investigating the possibility of epigenetic editing such as CRISPR-dCas9 (Clustered Regularly Interspaced Short Palindromic Repeats/deactivated CRISPR-associated protein 9) technologies, for targeting and modifying cancer related epigenetic alterations. A revolutionary form of precision cancer treatment called CRISPR-dCas9 is derived from the bacterial CRISPR-Cas (CRISPR-associated nuclease) system. CRISPR-dCas9 can be combined with epigenetic effectors (EE) to alter malignant epigenetic characteristics associated with cancer. The purpose of this review article is to provide a thorough analysis of recent advancements in utilizing CRISPR-dCas9 technology to target and modify epigenetic changes associated with cancer. This review aims to summarize the latest research developments, evaluate the effectiveness and limitations of CRISPR-dCas9 applications in cancer therapy, identify key challenges such as delivery methods and explore future directions for improving and expanding these technologies. Here, we address the various obstacles that may arise in clinical applications while showcasing the latest advancements and potential future uses of CRISPR-Cas9 in cancer therapy. [ABSTRACT FROM AUTHOR]

Niosomal and Polymeric-based nanoparticles offer advantages over conventional systems, such as targeted drug delivery and reduced toxicity. These nanoparticles are very promising due to their high drug loading capacity, stability, and ability to target specific cells or tissues. However, developing these nanoparticles presents challenges and requires careful selection of materials. These particles can deliver both hydrophilic and hydrophobic drugs and have applications in cancer therapy, gene therapy, and vaccination. This review aims to provide a comprehensive understanding of the current state of the art in the field of niosomal and polymeric nanoparticle design and optimization for efficient targeted drug delivery. [ABSTRACT FROM AUTHOR]

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Despite breakthroughs in the development of cancer diagnosis and therapy, most current therapeutic approaches lack precise specificity and sensitivity, resulting in damage to healthy cells. Selective delivery of anti-cancer agents is thus an important goal of cancer therapy. Scorpion venom (SV) and/or body parts have been used since early civilizations for medicinal purposes, and in cultures, SV is still applied to the treatment of several diseases including cancer. SV contains numerous active micro and macromolecules with diverse pharmacological effects. These include potent anti-microbial, anti-viral, anti-inflammatory, and anti-cancer properties. This review focuses on the recent advances of SV-derived peptides as promising anti-cancer agents and their diagnostic and therapeutic potential applications in cancers such as glioma, breast cancer, prostate cancer, and colon cancer. Well-characterized SV-derived peptides are thus needed to serve as potent and selective adjuvant therapy for cancer, to significantly enhance the patients' survival and wellbeing. [ABSTRACT FROM AUTHOR]

Introduction: Poly(ADP-ribose) polymerase 1 (PARP1) inhibition has become a major target in anticancer therapy. While PARP inhibitors (PARPi) are approved for homologous recombination (HR) deficient cancers, therapeutic resistance is a challenge and PARPi are now being investigated in cancers lacking HR deficiencies. This creates a need to develop molecular and imaging biomarkers of PARPi response to improve patient selection and circumvent therapeutic resistance. Areas covered: PubMed and clinicaltrials.gov were queried for studies on PARPi resistance and imaging. This review summarizes established and emerging resistance mechanisms to PARPi, and the current state of imaging and theragnostic probes for PARPi, including fluorescently labeled and radiolabeled probes. Expert opinion: While progress has been made in understanding PARPi therapeutic resistance, clinical evidence remains lacking and relatively little is known regarding PARPi response outside of HR deficiencies. Continued research will clarify the importance of known biomarkers and resistance mechanisms in patient cohorts and the broader utility of PARPi. Progress has also been made in PARPi imaging, particularly with radiolabeled probes, and both imaging and theragnostic probes have now reached clinical validation. Reducing abdominal background signal from probe clearance will broaden their applicability, and improvements to molecular synthesis and radiation delivery will increase their utility. [ABSTRACT FROM AUTHOR]

Efficient delivery of therapeutics to immune cells remains a formidable challenge for cancer immunotherapy. In this work, we demonstrate that an aptamer-driven DNA nanodevice, constructed through linkage of a synthetic immunostimulant (Toll-like receptor 9 agonist: CpG motif) to an aptamer, could significantly enhance the immunostimulatory activity by facilitating the uptake and retention of therapeutics in macrophages. Systemic administration of the DNA nanodevice results in efficient tumor growth inhibition in both breast cancer and melanoma mouse models. Our studies suggest that the DNA nanodevice leads to reeducation of tumor-associated macrophages and ultimately to reversing the tumor immune microenvironment. The strategy for aptamer-mediated and vehicle-free delivery of immunostimulatory oligonucleotides provides a potential platform for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Hydrogels are promising candidates for the delivery of therapeutics in the treatment of human cancers. Regarding to the biocomaptiiblity, high drug and encapsulation efficacy and adjustable physico-chemical features, the hydrogels have been widely utilized for the delivery of chemotherapy drugs. Doxorubicin (DOX) is one of the most common chemotherapy drugs used in cancer therapy through impairing topoisomerase II function and increasing oxidative damage. However, the tumor cells have developed resistance into DOX-mediated cytotoxic impacts, requiring the delivery systems to increase internalization and anti-cancer activity of this drug. The hydrogels can deliver DOX in a sustained manner to maximize its anti-cancer activity, improving cancer elimination and reduction in side effects and drug resistance. The natural-based hydrogels such as chitosan, alginate and gelatin hydrogels have shown favourable biocompatibility and degradability in DOX delivery for tumor suppression. The hydrogels are able to co-deliver DOX with other drugs or genes to enhance drug sensitivity and mediate polychemotherapy, synergistically suppressing cancer progression. The incorporation of nanoparticles in the structure of hydrogels can improve the sustained release of DOX and enhancing intracellular internalization, accelerating DOX's cytotoxicity. Furthermore, the stimuli-responsive hydrogels including pH-, redox- and thermo-sensitive platforms are able to improve the specific release of DOX at the tumor site. The DOX-loaded hydrogels can be further employed in the clinic for the treatment of cancer patients and improving efficacy of chemotherapy. Highlights: Hydrogels are 3-dimensional polymeric networks for therapeutic delivery. Doxorubicin (DOX) efficacy has been challenged with drug resistance development. Hydrogels can deliver DOX in a sustained manner to enhance its anti-cancer function. Hydrogels co-deliver drugs and genes in increasing DOX sensitivity. Natural-based hydrogels, nanocomposite-incorporated hydrogels and stimuli-responsive types improve DOX cytotoxicity. [ABSTRACT FROM AUTHOR]

The burgeoning field of pharmacomicrobiomics offers promising insights into the intricate interplay between the microbiome and cancer, shaping responses to diverse treatment modalities. This review aims to analyze the molecular mechanisms underlying interactions between distinct microbiota types and cancer, as well as their influence on treatment outcomes. We explore how the microbiome impacts antitumor immunity, and response to chemotherapy, immunotherapy, and radiation therapy, unveiling its multifaceted roles in cancer progression and therapy resistance. Moreover, we discuss the challenges hindering the development of microbiome-based interventions in cancer therapy, including standardization, validation, and clinical translation. By synthesizing clinical evidence, we underscore the transformative potential of harnessing pharmacomicrobiomics in guiding cancer treatment decisions, paving the way for improved patient outcomes in clinical practice. [ABSTRACT FROM AUTHOR]

Cancer, including gastric cancer, has become a serious disease that jeopardizes public life. Currently, the main treatment methods are surgery, radiation therapy, and chemotherapy. One of the primary causes of death for patients with gastric cancer is drug resistance. Several mechanisms of anticancer drugs resistance have been reported, including changes in drugs transport and metabolism, mutations in drug targets, changes in DNA repair systems, inhibition of cell apoptosis and autophagy, gastric cancer stem cells, invasion and migration. It is becoming more widely known that non-coding RNAs, like circRNAs, play a critical role in the resistance of drugs used to treat gastric cancer. CircRNAs have a unique structure and function that is related to gastric cancer resistance, cell proliferation, apoptosis, autophagy, DNA repair systems, migration, and invasion. A clear understanding of the molecular mechanism of circRNAs mediated the resistance of gastric cancer drugs will open a new window for the treatment and management of gastric cancer. Therefore, in this review, we will summarize the current mechanism of drug resistance, and finally discuss the molecular mechanism of circRNAs in regulating the development of drug resistance in gastric cancer. [ABSTRACT FROM AUTHOR]

Advancing therapeutic effectiveness through the strategic co‐delivery of drugs in a sequential manner represents a compelling strategy. However, achieving precise and selective release of chemotherapeutic agents remains a formidable challenge. In this study, a co‐assembled Arginine‐Glycine‐Aspartate (RGD)‐functionalized dehydropeptide‐based gel loaded with magnetic liposomes and mesoporous silica‐coated gold nanorods is introduced. This composite system serves as a sophisticated tool to independently modulate the release of doxorubicin and methotrexate. The gel's properties are intricately tuned by the incorporation of liposomes or nanorods and/or the co‐assembly with an RGD‐functionalized peptide. Furthermore, the combined effects of sequential drug release, photothermia, and magnetic hyperthermia synergistically enhance therapeutic efficacy against 3D cancer cell cultures. Noteworthy attributes of the gel include its ability to orthogonally trigger loaded drugs, along with features such as injectability, rapid gelation, self‐healing, and mechanical properties suitable for drug delivery. Consequently, this versatile multimodal platform emerges as a promising option for therapeutic applications, particularly in the context of cancer therapy. [ABSTRACT FROM AUTHOR]

ABSTRACT Ataxia telangiectasia and Rad3‐related (ATR) kinase is one of the main regulators of cell response to DNA damage and replication stress. Effectiveness of ATR targeting in human cancers has been confirmed in preclinical studies and ATR inhibitors are currently developed clinically in human oncology. In the presented study, we tested the anticancer efficacy of ATR inhibitor berzosertib in an in vitro model of canine haematopoietic cancers. Using MTT assay and flow cytometry, we assessed the cytotoxicity of berzosertib in four established canine lymphoma and leukaemia cell lines and compared it with its activity against noncancerous canine cells. Further, we estimated the level of apoptosis in berzosertib‐treated cells via flow cytometry and assessed H2AX phosphorylation as a marker of DNA damage using western blot technique. In flow‐cytometric analysis, we also evaluated potential synergism between berzosertib and chlorambucil and assessed the influence of berzosertib on cell cycle disturbances induced by the drug. The results demonstrated that berzosertib, even without additional DNA damaging agent, can be effective against canine lymphoma and leukaemia cells at concentrations that were harmless for noncancerous cells, although sensitivity of individual cancer cell lines varied greatly. Cell death occurred through caspase‐dependent apoptosis via induction of DNA damage. Berzosertib also acted synergistically with chlorambucil, probably by preventing DNA damage repair as a consequence of S‐phase arrest abrogation. In conclusion, ATR inhibition may provide a new therapeutic option for the treatment of canine lymphomas and leukaemias, but further studies are required to determine potential biomarkers of their susceptibility. [ABSTRACT FROM AUTHOR]

Targeted delivery of therapeutic anticancer chimeric molecules enhances drug efficacy. Numerous studies have focused on developing novel treatments by employing cytokines, particularly interleukins, to inhibit the growth of cancer cells. In the present study, we fused interleukin 24 with the tumor-targeting peptide P20 through a rigid linker to selectively target cancer cells. The secondary structure, tertiary structure, and physicochemical characteristics of the constructed chimeric IL-24-P20 protein were predicted by using bioinformatics tools. In-silico analysis revealed that the fusion construct has a basic nature with 175 amino acids and a molecular weight of 20 kDa. By using the Rampage and ERRAT2 servers, the validity and quality of the fusion protein were evaluated. The results indicated that 93% of the chimeric proteins contained 90.1% of the residues in the favoured region, resulting in a reliable structure. Finally, docking and simulation studies were conducted via ClusPro and Desmond Schrödinger, respectively. Our results indicate that the constructed fusion protein exhibits excellent quality, interaction capabilities, validity, and stability. These findings suggest that the fusion protein is a promising candidate for targeted cancer therapy. [ABSTRACT FROM AUTHOR]

Immunotherapy has profoundly changed the treatment of gastric cancer, but only a minority of patients benefit from immunotherapy. Therefore, numerous studies have been devoted to clarifying the mechanisms underlying resistance to immunotherapy or developing biomarkers for patient stratification. However, previous studies have focused mainly on the tumor microenvironment. Systemic immune perturbations have long been observed in patients with gastric cancer, and the involvement of the peripheral immune system in effective anticancer responses has attracted much attention in recent years. Therefore, understanding the distinct types of systemic immune organization in gastric cancer will aid personalized treatment designed to pair with traditional therapies to alleviate their detrimental effects on systemic immunity or to directly activate the anticancer response of systemic immunity. Herein, this review aims to comprehensively summarize systemic immunity in gastric cancer, including perturbations in systemic immunity induced by cancer and traditional therapies, and the potential clinical applications of systemic immunity in the detection, prediction, prognosis and therapy of gastric cancer. [ABSTRACT FROM AUTHOR]

Thermal agents (TAs) have exhibited promise in clinical tests when utilized in cancer thermal therapy (TT). While rapid degradation of TAs may address safety concerns, it limits the thermal stability required for effective treatment. TAs, which possess exceptional thermal stability, experience gradual deterioration. There are few approaches that effectively address the trade-off between improving thermal stability and simultaneously boosting material deterioration. Here, we control the thermal character of tungsten disulfide (WS2)-based 2D materials by utilizing an M13 phage through Joule heating (the M13–WS2–PEG nanostructures were generated and termed a tripartite (T) nanostructure), and developed a T nanostructure-driven TT platform (we called it T-TT) for efficient thermal ablation of clinically relevant MCF-7 cells. A relative cell viability of ~59% was achieved, as well as onset time of degradation of ~0.5 week. The T-TT platform also discloses an energy density of 5.9 J/mL. Furthermore, the phage-conjugated WS2 can be utilized to achieve ultrasound imaging for disease monitoring. Therefore, this research not only presents a thermal agent that overcomes TA limitations, but also demonstrates a practical application of WS2-type material system in ultra-energy efficient and effective cancer therapy. [ABSTRACT FROM AUTHOR]

The increasing interest in bacteriophage technology has prompted its novel applications to treat different medical conditions, most interestingly cancer. Due to their high specificity, manipulability, nontoxicity, and nanosize nature, phages are promising carriers in targeted therapy and cancer immunotherapy. This approach is particularly timely, as current challenges in cancer research include damage to healthy cells, inefficiency in targeting, obstruction by biological barriers, and drug resistance. Some cancers are being kept at the forefront of phage research, such as colorectal cancer and HCC, while others like lymphoma, cervical cancer, and myeloma have not been retouched in a decade. Common mechanisms are immunogenic antigen display on phage coats and the use of phage as transporters to carry drugs, genes, and other molecules. To date, popular phage treatments being tested are gene therapy and phage-based vaccines using M13 and λ phage, with some vaccines having advanced to human clinical trials. The results from most of these studies have been promising, but limitations in phage-based therapies such as reticuloendothelial system clearance or diffusion inefficiency must be addressed. Before phage-based therapies for cancer can be successfully used in oncology practice, more in-depth research and support from local governments are required. [ABSTRACT FROM AUTHOR]

The vascular endothelium, a specialized monolayer of endothelial cells (ECs), is crucial for maintaining vascular homeostasis by controlling the passage of substances and cells. In the tumor microenvironment, Vascular Endothelial Growth Factor A (VEGF-A) drives tumor angiogenesis, leading to endothelial anergy and vascular immunosuppression—a state where ECs resist cytotoxic CD8+ T cell infiltration, hindering immune surveillance. Immunotherapies have shown clinical promise. However, their effectiveness is significantly reduced by tumor EC anergy. Anti-angiogenic treatments aim to normalize tumor vessels and improve immune cell infiltration. Despite their potential, these therapies often cause significant systemic toxicities, necessitating new treatments. The small GTPase Rap1B emerges as a critical regulator of Vascular Endothelial Growth Factor Receptor 2 (VEGFR2) signaling in ECs. Our studies using EC-specific Rap1B knockout mice show that the absence of Rap1B impairs tumor growth, alters vessel morphology, and increases CD8+ T cell infiltration and activation. This indicates that Rap1B mediates VEGF-A's immunosuppressive effects, making it a promising target for overcoming vascular immunosuppression in cancer. Rap1B shares structural and functional similarities with RAS oncogenes. We propose that targeting Rap1B could enhance therapies' efficacy while minimizing adverse effects by reversing endothelial anergy. We briefly discuss strategies successfully developed for targeting RAS as a model for developing anti-Rap1 therapies. [ABSTRACT FROM AUTHOR]

[Display omitted] Nanomedicines that combine reactive oxygen species (ROS)-responsive polyprodrug and photodynamic therapy have shown great potential for improving treatment efficacy. However, the consumption of ROS by overexpressed glutathione in tumor cells is a major obstacle for achieving effective ROS amplification and prodrug activation. Herein, we report a polyprodrug-based nanoparticle that can realize ROS amplification and cascaded drug release. The nanoparticle can respond to the high level of hydrogen peroxide in tumor microenvironment, achieving self-destruction and release of quinone methide. The quinone methide depletes intracellular glutathione and thus decreases the antioxidant capacity of cancer cells. Under laser irradiation, a large amount of ROS will be generated to induce cell damage and prodrug activation. Therefore, the glutathione-depleting polyprodrug nanoparticles can efficiently inhibit tumor growth by enhanced photodynamic therapy and cascaded locoregional chemotherapy. [ABSTRACT FROM AUTHOR]

Mitochondria, pivotal organelles crucial for energy generation, apoptosis regulation, and cellular metabolism, have spurred remarkable advancements in targeted material development. This review surveys recent breakthroughs in targeted mitochondrial nanomaterials, illuminating their potential in drug delivery, disease management, and biomedical imaging. This review approaches from various application perspectives, introducing the specific applications of mitochondria-targeted materials in cancer treatment, probes and imaging, and diseases treated with mitochondria as a therapeutic target. Addressing extant challenges and elucidating potential therapeutic mechanisms, it also outlines future development trajectories and obstacles. By comprehensively exploring the diverse applications of targeted mitochondrial nanomaterials, this review aims to catalyze innovative treatment modalities and diagnostic approaches in medical research. This review presents the latest advancements in mitochondria-targeted nanomaterials for biomedical applications, covering diverse fields such as cancer therapy, bioprobes, imaging, and the treatment of various systemic diseases. The novelty and significance of this work lie in its systematic analysis of the intricate relationship between mitochondria and different diseases, as well as the ingenious design strategies employed to harness the therapeutic potential of nanomaterials. By providing crucial insights into the development of mitochondria-targeted nanomaterials and their applications, this review offers a valuable resource for researchers working on innovative treatment modalities and diagnostic approaches. The scientific impact and interest to the readership lie in the identification of promising avenues for future research and the potential for clinical translation of these cutting-edge technologies. [Display omitted] [ABSTRACT FROM AUTHOR]

Background: For angioimmunoblastic T cell lymphoma (AITL), a rare cancer, no specific treatments are available and survival outcome is poor. We previously developed a murine model for AITL that mimics closely human disease and allows to evaluate new treatments. As in human AITL, the murine CD4+ follicular helper T (Tfh) cells are drivers of the malignancy. Therefore, chimeric antigen receptor (CAR) T cell therapy might represent a new therapeutic option. Methods: To prevent fratricide among CAR T cells when delivering an CD4-specific CAR, we used a lentiviral vector (LV) encoding an anti-CD4 CAR, allowing exclusive entry into CD8 T cells. Results: These anti-CD4CAR CD8-targeted LVs achieved in murine AITL biopsies high CAR-expression levels in CD8 T cells. Malignant CD4 Tfh cells were eliminated from the mAITL lymphoma, while the CAR + CD8 T cells expanded upon encounter with the CD4 receptor and were shaped into functional cytotoxic cells. Finally, in vivo injection of the CAR + CD8-LVs into our preclinical AITL mouse model carrying lymphomas, significantly prolonged mice survival. Moreover, the in vivo generated functional CAR + CD8 T cells efficiently reduced neoplastic T cell numbers in the mAITL tumors. Conclusion: This is the first description of in vivo generated CAR T cells for therapy of a T cell lymphoma. The strategy described offers a new therapeutic concept for patients suffering from CD4-driven T cell lymphomas. [ABSTRACT FROM AUTHOR]

While the influence of size on nanomaterial uptake has been extensively explored, it remains elusive how cells simultaneously respond to multiple, size‐varying particles due to the lack of a proper quantitative assay. In this study, a strategy named "metal‐doping engineering" is developed, and constructed a library of multi‐elemental alloys (MEAs) features precisely controlled size and dopant dosage for quantification with mass spectra. Next a comprehensive study of cellular uptake behaviors is conducted when treated with dual‐, triple‐, and quadra‐, size‐differing nanoparticles. Specifically, the exposure to triple‐, and quadra‐, size‐differing MEAs resulted in an unprecedented, enhanced uptake of counterpart in the middle size as 10/20 nm. Further efforts including RNA‐sequencing and photo‐affinity labeling‐assisted proteomics are devoted to uncovering the underlying mechanism, wherein the role of nonconical endocytic pathways in fast‐endophilin‐mediated endocytosis is uncovered. Given the capacity of MEAs as chaperones to facilitate the uptake of one featuring a predetermined size promoted to propose a straightforward, "bystander nanomaterials"‐assisted drug delivery strategy, whose superior dosage‐reduced radio‐sensitization performance and anti‐tumoral outcome are confirmed in vivo. [ABSTRACT FROM AUTHOR]

Innovative hybrid nanostructures have revolutionized modern therapy by combining different materials at the nanoscale, offering unique synergistic properties that enhance their functionality. These advancements are pivotal in areas such as targeted drug delivery, photothermal and photodynamic therapy, and gene delivery, where they significantly improve therapeutic outcomes. The article discusses the synthesis methods and characterization techniques of HNSs, providing a comprehensive analysis of their mechanisms of action in various therapeutic applications. Highlighted case studies demonstrate their efficacy in treating conditions such as cancer, neurodegenerative diseases, and cardiovascular disorders, underscoring their potential to bridge existing gaps in medical treatments. The review also emphasizes the need for continued innovation and interdisciplinary collaboration to optimize these nanostructures for clinical applications. Future research should focus on enhancing biocompatibility, targeting capabilities, and integrating advanced imaging techniques and AI-driven applications to further improve the precision and efficacy of HNSs in therapy. These advancements herald a new era in medical treatment, offering transformative solutions for complex diseases. [ABSTRACT FROM AUTHOR]

As global population ageing accelerates, cancer emerges as a predominant cause of mortality. Long non-coding RNAs (lncRNAs) play crucial roles in cancer cell growth and death, given their involvement in regulating downstream gene expression levels and numerous cellular processes. Cell death, especially non-apoptotic regulated cell death (RCD), such as ferroptosis, pyroptosis and necroptosis, significantly impacts cancer proliferation, invasion and metastasis. Understanding the interplay between lncRNAs and the diverse forms of cell death in cancer is imperative. Modulating lncRNA expression can regulate cancer onset and progression, offering promising therapeutic avenues. This review discusses the mechanisms by which lncRNAs modulate nonapoptotic RCDs in cancer, highlighting their potential as biomarkers for various cancer types. Elucidating the role of lncRNAs in cell death pathways provides valuable insights for personalised cancer interventions. [ABSTRACT FROM AUTHOR]

The combination of anti-angiogenic drugs and immune checkpoint inhibitors (ICIs) in the treatment of tumors is emerging as a way to improve ICIs-resistant tumor therapy. In addition, gut microbes (GMs) are involved in angiogenesis in the tumor microenvironment and are also associated with the antitumor function of immune checkpoint inhibitors. However, it is unclear whether gut microbes have a role in anti-tumor function in the combination of anti-angiogenic drugs and immune checkpoint inhibitors for cancer treatment. Endostatin, an angiogenesis inhibitor, has been widely used as an antiangiogenic therapy for cancer. We showed that combined therapy with an adenovirus encoding human endostatin, named Ad-E, and PD-1 blockade dramatically abrogated MC38 tumor growth. The structure of intestinal microbes in mice was changed after combination treatment. We found that the antitumor function of combination therapy was inhibited after the elimination of intestinal microbes. In mice with depleted microbiota, oral gavage of Bacteroides fragilis salvaged the antitumor effects of combination Ad-E and αPD-1 monoclonal antibody (mAb) to a certain extent. Further, Bacteroides fragilis could improve CD3+T cells, NK cells, and IFNγ+CD8+ T cells in the tumor microenvironment to inhibit tumor growth. Besides, Bacteroides fragilis might restore antitumor function by down-regulating isobutyric acid (IBA). Our results suggested that GMs may be involved in the combination of Ad-E and αPD-1 mAb for cancer treatment, which has oncological implications for tumor growth dynamics and cancer immune surveillance. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid carcinoma (ATC) is the most aggressive thyroid cancer, and it has a poor prognosis and high probability of metastatic recurrence. The long-term survival of cancer cells depends on their ability to settle in a favorable environment. Cancer cells interact with other cells in the tumor microenvironment to shape the "soil" and make it suitable for cell growth by forming an extremely complex tumor ecosystem. The extracellular matrix (ECM) is an essential component of the tumor ecosystem, and its biological and mechanical changes strongly affect tumor invasion, metastasis, immune escape and drug resistance. Compared to normal tissues, biological processes, such as collagen synthesis and ECM signaling, are significantly activated in ATC tissues. However, how ATC triggers changes in the properties of the ECM and its interaction with the ECM remain poorly characterized. Therefore, an in-depth study of the regulatory mechanism of the abnormal activation of ECM signaling in ATC is highly important for achieving the therapeutic goal of exerting antitumor effects by destroying the "soil" in which cancer cells depend for survival. In this research, we revealed the aberrant activation state of ECM signaling in ATC progression and attempted to uncover the potential mechanism of action of ECM components in ATC, with the aim of providing new drug targets for ATC therapy. [ABSTRACT FROM AUTHOR]

A new type of hybrid polymer particles capable of carrying the cytostatic drug doxorubicin and labeled with a gallium compound was prepared. These microparticles consist of a core and a hydrogel shell, which serves as the structural matrix. The shell can be employed to immobilize gallium oxide hydroxide (GaOOH) nanoparticles and the drug, resulting in hybrid beads with sizes of approximately 3.81 ± 0.09 μm. The microparticles exhibit the ability to incorporate a remarkably large amount of doxorubicin, approximately 0.96 mg per 1 mg of the polymeric carrier. Additionally, GaOOH nanoparticles can be deposited within the hydrogel layer at an amount of 0.64 mg per 1 mg of the carrier. These nanoparticles, resembling rice grains with an average size of 593 nm by 155 nm, are located on the surface of the polymer carrier. In vitro studies on breast and colon cancer cell lines revealed a pronounced cytotoxic effect of the hybrid polymer particles loaded with doxorubicin, indicating their potential for cancer therapies. Furthermore, investigations on doping the hybrid particles with the Ga-68 radioisotope demonstrated their potential application in positron emission tomography (PET) imaging. The proposed structures present a promising theranostic platform, where particles could be employed in anticancer therapies while monitoring their accumulation in the body using PET. [ABSTRACT FROM AUTHOR]

The androgen receptor (AR) is an attractive target for treating prostate cancer, considering its role in the development and progression of localized and metastatic prostate cancer. The high global mortality burden of prostate cancer, despite medical treatments such as androgen deprivation or AR antagonist therapy, highlights the need to explore alternative strategies. One strategy involves the use of heterobifunctional degraders, also known as proteolysis‐targeting chimeras, which are novel small‐molecule therapeutics that inhibit amplified or mutated targets. Here, the study reports a novel cereblon‐based AR degrader, UBX‐390, and demonstrates its superior activity over established AR degraders, such as ARV‐110 or ARCC‐4, in prostate cancer cells under short‐ and long‐term treatment conditions. UBX‐390 suppresses chromatin binding and gene expression of AR and demonstrates substantial efficacy in the degradation of AR mutants in patients with treatment‐resistant prostate cancer. UBX‐390 is presented as an optimized AR degrader with remarkable potential for treating castration‐resistant prostate cancer. [ABSTRACT FROM AUTHOR]

Metal oxide nanoparticles(NPs) contain unique properties which have made them attractive agents in cancer treatment. The CuO nanoparticles were green synthesized using walnut shell powder in different calcination temperatures (400°, 500°, 700°, and 900 °C). The CuO nanoparticles are characterized by FTIR, XRD, BET, SEM and DLS analyses. SEM and DLS analyses showed that by increasing the required calcination temperature for synthesizing the NPs, their size was increased. DPPH analysis displayed no significant anti-oxidative properties of the CuO NPs. The MTT analysis showed that all synthesized CuO NPs exhibited cytotoxic effects on MCF-7, HCT-116, and HEK-293 cell lines. Among the CuO NPs, the CuO-900 NPs showed the least cytotoxic effect on the HEK-293 cell line (IC50 = 330.8 µg/ml). Hoechst staining and real-time analysis suggested that the CuO-900 NPs induced apoptosis by elevation of p53 and Bax genes expression levels. Also, the CuO-900 NPs increased the Nrf-2 gene expression level in MCF-7 cells, despite the HCT-116 cells. As can be concluded from the results, the CuO-900 NPs exerted promising cytotoxic effects on breast and colon cancer cells. [ABSTRACT FROM AUTHOR]

Recent experimental investigations have demonstrated that a substantial amount of H−/D− ions can be formed by thermal desorption processes. Based on these new findings, new mini axial and coaxial-type neutron tubes have been developed for the production of high or low-energy neutrons via the d-d, d-10B, d-7Li or p-7Li nuclear reactions. By operating these mini neutron tubes with a high frequency AC high-voltage supply, short pulses of high intensity neutron beams can be generated. Multiple applications, such as carbon and well logging, neutron imaging, cancer therapy, medical isotope production, fission reactor start-up, fusion reactor material evaluation, homeland security and space exploration can be performed with the subcompact neutron generator system. It is shown that the performance of these new mini neutron tubes can exceed those of the conventional plasma-based neutron sources. [ABSTRACT FROM AUTHOR]

Cardamom (cardamum) is a spice produced from the seeds of several Elettaria and Amomum plants of the Zingiberaceae family. Cardamom has been demonstrated to offer numerous benefits, including its antioxidant, antimicrobial, anti-inflammatory, and other metabolic (anti-diabetic) properties, and its potential to reduce cancer risk. Recently, researchers have extracted and tested multiple phytochemicals from cardamom to assess their potential effectiveness against various types of human malignancy. These studies have indicated that cardamom can help overcome drug resistance to standard chemotherapy and protect against chemotherapy-induced toxicity due to its scavenging properties. Furthermore, chemical compounds in cardamom, including limonene, cymene, pinene, linalool, borneol, cardamonin, indole-3-carbinol, and diindolylmethane, primarily target the programmed cell death lignin-1 gene, which is more prevalent in cancer cells than in healthy cells. This review provides the medicinal properties and pharmacological uses of cardamom, its cellular effects, and potential therapeutic uses in cancer prevention and treatment, as well as its use in reducing drug resistance and improving the overall health of cancer patients. Based on previous preclinical studies, cardamom shows significant potential as an anti-cancer agent, but further exploration for clinical use is warranted due to its diverse mechanisms of action. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are leading the way in nanotechnological innovation, combining the captivating properties of silver with the accuracy of nanoscale engineering, thus revolutionizing material science. Three main techniques arise within the alchemical domains of AgNP genesis: chemical, physical, and biological synthesis. Each possesses its distinct form of magic for controlling size, shape, and scalability—key factors necessary for achieving expertise in the practical application of nanoparticles. The story unravels, describing the careful coordination of chemical reduction, the environmentally sensitive charm of green synthesis utilizing plant extracts, and the precise accuracy of physical techniques. AgNPs are highly praised in the field of healthcare for their powerful antibacterial characteristics. These little warriors display a wide-ranging attack against bacteria, fungi, parasites, and viruses. Their critical significance in combating hospital-acquired and surgical site infections is highly praised, serving as a beacon of hope in the fight against the challenging problem of antibiotic resistance. In addition to their ability to kill bacteria, AgNPs are also known to promote tissue regeneration and facilitate wound healing. The field of cancer has also observed the adaptability of AgNPs. The review documents their role as innovative carriers of drugs, specifically designed to target cancer cells with accuracy, minimizing harm to healthy tissues. Additionally, it explores their potential as cancer therapy or anticancer agents capable of disrupting the growth of tumors. In the food business, AgNPs are utilized to enhance the durability of packing materials and coatings by infusing them with their bactericidal properties. This results in improved food safety measures and a significant increase in the duration that products can be stored, thereby tackling the crucial issue of food preservation. This academic analysis recognizes the many difficulties that come with the creation and incorporation of AgNPs. This statement pertains to the evaluation of environmental factors and the effort to enhance synthetic processes. The review predicts future academic pursuits, envisioning progress that will enhance the usefulness of AgNPs and increase their importance from being new to becoming essential within the realms of science and industry. Besides, AgNPs are not only a subject of scholarly interest but also a crucial component in the continuous effort to tackle some of the most urgent health and conservation concerns of contemporary society. This review aims to explore the complex process of AgNP synthesis and highlight their numerous uses, with a special focus on their growing importance in the healthcare and food business sectors. This review invites the scientific community to explore the extensive possibilities of AgNPs in order to fully understand and utilize their potential. [ABSTRACT FROM AUTHOR]

Background: Breast cancer incidence and mortality exhibit a rising trend globally among both premenopausal and postmenopausal women, suggesting that there are serious errors in our preventive and therapeutic measures. Purpose: Providing a series of valuable, but misunderstood inventions highlighting the role of increasing estrogen signaling in prevention and therapy of breast cancer instead of its inhibition. Results: 1. Breast cells and breast cancer cells with germline BRCA1/2 mutations similarly show defects in liganded estrogen receptor (ER) signaling, demonstrating its role in genomic instability and cancer initiation. 2. In breast tumors, the increased expression of special receptor family maybe an effort for self-directed improvement of genomic defects, while the weakness or loss of receptors indicates a defect requiring medical repair. 3. ER overexpression in breast cancer cells is capable of strengthening estrogen signaling and DNA repair, while in ER negative tumors, HER2 overexpression tries to upregulate unliganded ER activation and genome stabilization. 4. ER-positive breast cancers responsive to endocrine therapy may show a compensatory ER overexpression resulting in a transient tumor response. Breast cancers non-responsive to antiestrogen treatment exhibit HER2-overexpression for compensating the complete inhibition of hormonal ER activation. 5. In breast tumors, somatic mutations serve upregulation of ER activation via liganded or unliganded pathway helping genome stabilization and apoptotic death. 6. The mutual communication between breast cancer and its inflammatory environment is a wonderful partnership among cells fighting for genome stabilization and apoptotic death of tumor. 7. In breast cancers, there is no resistance to genotoxic or immune blocker therapies, but rather, the nonresponsive tumor cells exhaust all compensatory possibilities against therapeutic damages. Conclusions: Understanding the behavior and ambition of breast cancer cells may achieve a turn in therapy via applying supportive care instead of genotoxic measures. [ABSTRACT FROM AUTHOR]

The search for new antineoplastic agents is imperative, as cancer remains one of the most preeminent causes of death worldwide. Since the discovery of the therapeutic potential of cisplatin, the study of metallodrugs in cancer chemotherapy acquired increasing interest. Starting from cisplatin derivatives, such as oxaliplatin and carboplatin, in the last years, different compounds were explored, employing different metal centers such as iron, ruthenium, gold, and palladium. Nonetheless, metallodrugs face several drawbacks, such as low water solubility, rapid clearance, and possible side toxicity. Encapsulation has emerged as a promising strategy to overcome these issues, providing both improved biocompatibility and protection of the payload from possible degradation in the biological environment. In this respect, liposomes, which are spherical vesicles characterized by an aqueous core surrounded by lipid bilayers, have proven to be ideal candidates due to their versatility. In fact, they can encapsulate both hydrophilic and hydrophobic drugs, are biocompatible, and their properties can be tuned to improve the selective delivery to tumour sites exploiting both passive and active targeting. In this review, we report the most recent findings on liposomal formulations of metallodrugs, with a focus on encapsulation techniques and the obtained biological results. [ABSTRACT FROM AUTHOR]

Drug resistance remains a critical barrier in cancer therapy, diminishing the effectiveness of chemotherapeutic, targeted, and immunotherapeutic agents. Overexpression of proteins such as B-cell lymphoma 2 (Bcl-2), inhibitor of apoptosis proteins (IAPs), protein kinase B (Akt), and P-glycoprotein (P-gp) in various cancers leads to resistance by inhibiting apoptosis, enhancing cell survival, and expelling drugs. Although several inhibitors targeting these proteins have been developed, their clinical use is often hampered by systemic toxicity, poor bioavailability, and resistance development. Nanoparticle-based drug delivery systems present a promising solution by improving drug solubility, stability, and targeted delivery. These systems leverage the Enhanced Permeation and Retention (EPR) effect to accumulate in tumor tissues, reducing off-target toxicity and increasing therapeutic efficacy. Co-encapsulation strategies involving anticancer drugs and resistance inhibitors within nanoparticles have shown potential in achieving coordinated pharmacokinetic and pharmacodynamic profiles. This review discusses the mechanisms of drug resistance, the limitations of current inhibitors, and the advantages of nanoparticle delivery systems in overcoming these challenges. By advancing these technologies, we can enhance treatment outcomes and move towards more effective cancer therapies. [ABSTRACT FROM AUTHOR]

Cancer remains a formidable challenge in the field of medicine, necessitating innovative therapeutic strategies to combat its relentless progression. The cell cycle, a tightly regulated process governing cell growth and division, plays a pivotal role in cancer development. Dysregulation of the cell cycle allows cancer cells to proliferate uncontrollably. Therapeutic interventions designed to disrupt the cell cycle offer promise in restraining tumor growth and progression. Telomerase, an enzyme responsible for maintaining telomere length, is often overactive in cancer cells, conferring them with immortality. Targeting telomerase presents an opportunity to limit the replicative potential of cancer cells and hinder tumor growth. Angiogenesis, the formation of new blood vessels, is essential for tumor growth and metastasis. Strategies aimed at inhibiting angiogenesis seek to deprive tumors of their vital blood supply, thereby impeding their progression. Metastasis, the spread of cancer cells from the primary tumor to distant sites, is a major challenge in cancer therapy. Research efforts are focused on understanding the underlying mechanisms of metastasis and developing interventions to disrupt this deadly process. This review provides a glimpse into the multifaceted approach to cancer therapy, addressing critical aspects of cancer biology—cell cycle regulation, telomerase activity, angiogenesis, and metastasis. Through ongoing research and innovative strategies, the field of oncology continues to advance, offering new hope for improved treatment outcomes and enhanced quality of life for cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Antisense oligonucleotide (ASO)-based drugs are a new class of compounds. In this review, we will discuss ASO technology, including improved delivery systems, enhanced stability, increased specificity, and challenges such as off-target effects and immune responses. ASO shows potential in cancer treatment by inhibiting the cell signaling pathways implicated in cancer progression. The inhibition of Grb2 is a potential target for ASO in leukemia treatment. This review may significantly impact the scientific community by providing a comprehensive overview of ASO-based therapies. Advancements in our comprehension of tumor biology and chemoresistance have spurred the development of treatments that precisely target specific molecules within the body. Despite the expanding landscape of therapeutic options, there persists a demand for innovative approaches to address unmet clinical needs. RNA therapeutics have emerged as a promising frontier in this realm, offering novel avenues for intervention such as RNA interference and the utilization of antisense oligonucleotides (ASOs). ASOs represent a versatile class of therapeutics capable of selectively targeting messenger RNAs (mRNAs) and silencing disease-associated proteins, thereby disrupting pathogenic processes at the molecular level. Recent advancements in chemical modification and carrier molecule design have significantly enhanced the stability, biodistribution, and intracellular uptake of ASOs, thereby bolstering their therapeutic potential. While ASO therapy holds promise across various disease domains, including oncology, coronary angioplasty, neurological disorders, viral, and parasitic diseases, our review manuscript focuses specifically on the application of ASOs in targeted cancer therapies. Through a comprehensive examination of the latest research findings and clinical developments, we delve into the intricacies of ASO-based approaches to cancer treatment, shedding light on their mechanisms of action, therapeutic efficacy, and prospects. [ABSTRACT FROM AUTHOR]

Near-infrared-II (NIR-II) photothermal therapy is emerging as a cutting-edge modality for tumor ablation due to its good biosafety, high penetration ability and spatiotemporal controllability. Despite efforts, establishing a link between cellular metabolic regulation and photothermal performance is still promising in synergistic cancer therapy. Herein, we developed a core-shell semiconducting polymer@metal-phenolic network (SP@GFP) nanomotor by assembling diphenol-terminated cisplatin prodrug ligand (cPt-DA) and iron (III) (Fe3+) through metal coordination on SP particles in the presence of GOx and DSPE-PEG-cRGD, for NIR-II-propelled self-propulsion and synergistic cancer therapy. Remotely driving the SP@GFP nanomotor with an NIR-II laser through a thermophoresis mechanism would allow for in-depth penetration and accumulation. The synergistic photothermal effect and continuous Fe2+-mediated ROS generation of SP@GFP nanomotor could activate photothermal, chemotherapeutic effects and ferroptosis pathway for cancer cells through reshaping cellular metabolic pathways (HSP and GPX4). By combining the concepts of chemotherapeutic prodrugs, catalytic ROS generation, photothermal response and cellular metabolic regulation, the NIR-II laser-controlled core-shell SP@GFP nanomotor displayed improved outcomes for enhanced cancer therapy through synergistic oxidative stress-photothermo modulation. • A NIR-II-powered core-shell SP@GFP prodrug nanomotor was constructed through metal coordination assembly for enhanced cancer therapy; • NIR-II laser propelled the propulsion of SP@GFP nanomotor through thermophoresis mechanism for in depth penetration and accumulation. • Therapeutic outcomes were improved through synergistic modulating oxidative stress and photothermal performance. [Display omitted] [ABSTRACT FROM AUTHOR]

Natural products have proven to be promising anti-cancer agents due to their diverse chemical structures and bioactivity. This review examines their central role in cancer treatment, focusing on their mechanisms of action and therapeutic benefits. Medicinal plants contain bioactive compounds, such as flavonoids, alkaloids, terpenoids and polyphenols, which exhibit various anticancer properties. These compounds induce apoptosis, inhibit cell proliferation and cell cycle progression, interfere with microtubule formation, act on topoisomerase targets, inhibit angiogenesis, modulate key signaling pathways, improve the tumor microenvironment, reverse drug resistance and activate immune cells. Herbal anti-cancer drugs offer therapeutic advantages, particularly selective toxicity against cancer cells, reducing the adverse side effects associated with conventional chemotherapy. Recent studies and clinical trials highlight the benefits of herbal medicines in alleviating side effects, improving tolerance to chemotherapy and the occurrence of synergistic effects with conventional treatments. For example, the herbal medicine SH003 was found to be safe and potentially effective in the treatment of solid cancers, while Fucoidan showed anti-inflammatory properties that are beneficial for patients with advanced cancer. The current research landscape on herbal anticancer agents is extensive. Numerous studies and clinical trials are investigating their efficacy, safety and mechanisms of action in various cancers such as lung, prostate, breast and hepatocellular carcinoma. Promising developments include the polypharmacological approach, combination therapies, immunomodulation and the improvement of quality of life. However, there are still challenges in the development and use of natural products as anti-cancer drugs, such as the need for further research into their mechanisms of action, possible drug interactions and optimal dosage. Standardizing herbal extracts, improving bioavailability and delivery, and overcoming regulatory and acceptance hurdles are critical issues that need to be addressed. Nonetheless, the promising anticancer effects and therapeutic benefits of natural products warrant further investigation and development. Multidisciplinary collaboration is essential to advance herbal cancer therapy and integrate these agents into mainstream cancer treatment. [ABSTRACT FROM AUTHOR]

Cell death regulation is essential for tissue homeostasis and its dysregulation often underlies cancer development. Understanding the different pathways of cell death can provide novel therapeutic strategies for battling cancer. This review explores several key cell death mechanisms of apoptosis, necroptosis, autophagic cell death, ferroptosis, and pyroptosis. The research gap addressed involves a thorough analysis of how these cell death pathways can be precisely targeted for cancer therapy, considering tumor heterogeneity and adaptation. It delves into genetic and epigenetic factors and signaling cascades like the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) and mitogen‐activated protein kinase/extracellular signal‐regulated kinase (MAPK/ERK) pathways, which are critical for the regulation of cell death. Additionally, the interaction of the microenvironment with tumor cells, and particularly the influence of hypoxia, nutrient deprivation, and immune cellular interactions, are explored. Emphasizing therapeutic strategies, this review highlights emerging modulators and inducers such as B cell lymphoma 2 (BCL2) homology domain 3 (BH3) mimetics, tumour necrosis factor‐related apoptosis‐inducing ligand (TRAIL), chloroquine, and innovative approaches to induce ferroptosis and pyroptosis. This review provides insights into cancer therapy's future direction, focusing on multifaceted approaches to influence cell death pathways and circumvent drug resistance. This examination of evolving strategies underlines the considerable clinical potential and the continuous necessity for in‐depth exploration within this scientific domain. [ABSTRACT FROM AUTHOR]

Edible mushrooms are not only a valued culinary ingredient but also have several potential medicinal and industrial applications. They are a rich source of protein, fiber, vitamins, minerals, and bioactive compounds such as polysaccharides and terpenoids, and thus have the capacity to support human health. Some species have been shown to have antioxidant, anti-inflammatory, anticancer, and immunomodulatory properties. We have therefore attempted to summarize the potential properties of the edible mushrooms popular in Poland, in the Roztocze area. [ABSTRACT FROM AUTHOR]

We aimed to perform a comprehensive study on the development and characterization of silymarin (Syl)-loaded niosomes as potential drug delivery systems. The results demonstrate significant novelty and promising outcomes in terms of morphology, size distribution, encapsulation efficiency, in vitro release behavior, free energy profiles of Syl across the niosome bilayer, hydrogen bonding interactions, antimicrobial properties, cytotoxicity, and in vivo evaluations. The physical appearance, size, and morphology assessment of free niosomes and Syl-loaded niosomes indicated stable and well-formed vesicular structures suitable for drug delivery. Transmission electron microscopy (TEM) analysis revealed spherical shapes with distinct sizes for each formulation, confirming uniform distribution. Dynamic light scattering (DLS) analysis confirmed the size distribution results with higher polydispersity index for Syl-loaded niosomes. The encapsulation efficiency of Syl in the niosomes was remarkable at approximately 91%, ensuring protection and controlled release of the drug. In vitro release studies showed a sustained release profile for Syl-loaded niosomes, enhancing therapeutic efficacy over time. Free energy profiles analysis identified energy barriers hindering Syl permeation through the niosome bilayer, emphasizing challenges in drug delivery system design. Hydrogen bonding interactions between Syl and niosome components contributed to energy barriers, impacting drug permeability. Antimicrobial assessments revealed significant differences in inhibitory effects against S. aureus and E. coli. Cytotoxicity evaluations demonstrated the superior tumor-killing potential of Syl-loaded niosomes compared to free Syl. In vivo studies indicated niosome formulations' safety profiles in terms of liver and kidney parameters compared to bulk Syl, showcasing potential for clinical applications. Overall, this research highlights the promising potential of Syl-loaded niosomes as effective drug delivery systems with enhanced stability, controlled release, and improved therapeutic outcomes. [ABSTRACT FROM AUTHOR]