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Despite the recent wide investigation on active cancer drug delivery, there are still strong medical unmet needs for active tumor‐environment responsive cancer drug delivery in terms of spatiotemporal control. Herein, a biohybrid system of pH‐responsive peptide nanotubes (PNTs)‐coated microalgae for active cancer drug delivery in response to the tumor‐environment is developed. The amphiphilic PNTs are effectively used to encapsulate cancer drugs and coat the living microalgae of C. reinhardtii by electrostatic interactions. The drug‐loaded PNTs‐based biohybrid microalgae maintain agile movement with phototaxis behavior. After in vitro characterization and cytotoxicity assessment, it is shown that the biohybrid microalgae could be phototactically localized to the cancer cells and pH‐responsively disassembled to release cancer drugs in a controlled manner. Finally, with the encapsulation of paclitaxel, the statistically significant suppression of tumor growth in xenograft tumor model animals is successfully demonstrated. Taken together, the feasibility of the multifunctional microrobotic platform for advanced cancer therapy is confirmed. [ABSTRACT FROM AUTHOR]

Neutrophil extracellular traps (NETs) formed by neutrophils are netlike scaffolds that mainly contain DNA and a variety of granule proteins. Many stimuli can lead to the NET formation through independent molecular pathways. Clinically, the abundance of NETs is correlated with poor tumor prognosis. The biological actions of NETs are complex and diverse, including promoting tumor progression, awakening the dormant cancer cells, and resulting in immunosuppression in support of tumor growth and metastasis. Therefore, NET‐associated pathological processes provide an important clue for both diagnostic imaging and alternative therapies for many kinds of cancers. In recent years, scientists' efforts have focused on developing novel imaging probes to visualize NETs and therapeutic strategies by degrading NETs or inhibiting its formation to block their pro‐tumoral functions. In this review, the development and evaluation of NETs‐targeted imaging and intervention progress for tumor therapy are focused on. [ABSTRACT FROM AUTHOR]

Contemporary anticancer therapies frequently have different efficacy and side effects in men and women. Yet, whether women are well‐represented in pivotal trials supporting contemporary anticancer drugs is unknown. Leveraging the Drugs@FDA database, clinicaltrials.gov, MEDLINE, and publicly available FDA‐drug‐reviews, we identified all pivotal (phase II and III) non‐sex specific trials supporting FDA‐approval of anticancer drugs (1998–2018). Observed‐enrollment‐rates were compared to expected‐population‐rates derived from concurrent US‐National‐Cancer‐Institute's Surveillance‐Epidemiology‐and‐End‐Results (SEER) reported rates and US‐Census databases. Primary outcome was the proportional representation of women across trials, evaluated by a participation‐to‐prevalence ratio (PPR), according to cancer type. Secondary outcome was the report of any sex‐specific analysis of efficacy and/or safety, irrespective of treatment‐arm. Overall, there were 148 trials, enrolling 60,216 participants (60.5 ± 4.0 years, 40.7% female, 79.1% biologic, targeted, or immune‐based therapies) evaluating 99 drugs. Sex was reported in 146 (98.6%) trials, wherein 40.7% (24,538) were women, compared to 59.3% (35,678) men (p <.01). Altogether, women were under‐represented in 66.9% trials compared to the proportional incidence of cancers by respective disease type; weight‐average PPR of 0.91 (relative difference: ‐9.1%, p <.01). Women were most under‐represented in gastric (PPR = 0.63), liver (PPR = 0.71), and lung (PPR =.81) cancer trials. Sex‐based safety data was reported in 4.0% trials. There was no association between adequate female enrollment and drug efficacy (HR: 0.616 vs. 0.613, p =.96). Over time, there was no difference in the percentage of women recruited into clinical trials. Among pivotal clinical trials supporting contemporary FDA‐approved cancer drugs, women were frequently under‐represented and sex‐specific‐efficacy and safety‐outcomes were commonly not reported. [ABSTRACT FROM AUTHOR]

Over the past decades, medicine has made enormous progress, revolutionized by modern technologies and innovative therapeutic approaches. One of the most exciting branches of these developments is photodynamic therapy (PDT). Using a combination of light of a specific wavelength and specially designed photosensitizing substances, PDT offers new perspectives in the fight against cancer, bacterial infections, and other diseases that are resistant to traditional treatment methods. In today's world, where there is a growing problem of drug resistance, the search for alternative therapies is becoming more and more urgent. Imagine that we could destroy cancer cells or bacteria using light, without the need to use strong chemicals or antibiotics. This is what PDT promises. By activating photosensitizers using appropriately adjusted light, this therapy can induce the death of cancer or bacterial cells while minimizing damage to surrounding healthy tissues. In this work, we will explore this fascinating method, discovering its mechanisms of action, clinical applications, and development prospects. We will also analyze the latest research and patient testimonies to understand the potential of PDT for the future of medicine. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new discovered regulated cell death triggered by the ferrous ion (Fe2+)-dependent accumulation of lipid peroxides associated with cancer and many other diseases. The mechanism of ferroptosis includes oxidation systems (such as enzymatic oxidation and free radical oxidation) and antioxidant systems (such as GSH/GPX4, CoQ10/FSP1, BH4/GCH1 and VKORC1L1/VK). Among them, ferroptosis suppressor protein 1 (FSP1), as a crucial regulatory factor in the antioxidant system, has shown a crucial role in ferroptosis. FSP1 has been well validated to ferroptosis in three ways, and a variety of intracellular factors and drug molecules can alleviate ferroptosis via FSP1, which has been demonstrated to alter the sensitivity and effectiveness of cancer therapies, including chemotherapy, radiotherapy, targeted therapy and immunotherapy. This review aims to provide important frameworks that, bring the regulation of FSP1 mediated ferroptosis into cancer therapies on the basis of existing studies. [ABSTRACT FROM AUTHOR]

Gastrointestinal cancer is a significant global health burden, necessitating the development of novel therapeutic strategies. Emerging evidence has highlighted the potential of targeting ferritinophagy as a promising approach for the treatment of gastrointestinal cancer. Ferritinophagy is a form of selective autophagy that is mediated by the nuclear receptor coactivator 4 (NCOA4). This process plays a crucial role in regulating cellular iron homeostasis and has been implicated in various pathological conditions, including cancer. This review discusses the molecular mechanisms underlying ferritinophagy and its relevance to gastrointestinal cancer. Furthermore, we highlight the potential therapeutic implications of targeting ferritinophagy in gastrointestinal cancer. Several approaches have been proposed to modulate ferritinophagy, including small molecule inhibitors and immunotherapeutic strategies. We discuss the advantages and challenges associated with these therapeutic interventions and provide insights into their potential clinical applications. [ABSTRACT FROM AUTHOR]

Patients who undergo resection for melanoma face challenges, such as delayed healing and radiation dermatitis. Moreover, incomplete tumor resection is a key factor contributing to poor prognosis and increased recurrence rates. However, a therapeutic platform that can effectively prevent tumor recurrence and promote wound healing remains a challenge. Hence, a pioneering approach is presented using melanoma‐derived cancer cell membrane (CM) as a tumor antigen to encapsulate copper (Cu)‐based metal‐organic framework (MOF) nanomaterials to fabricate nanomaterials termed MOF@CM. Then MOF@CM is adsorbed onto polydopamine (PDA)‐modified poly lactic‐co‐glycolic acid (PLGA) porous microspheres (PLGA/PDA) to develop the copper nanomaterials‐decorated microspheres termed PLGA/PDA‐CCM (PLGA/PDA loaded with CM‐coated MOF). It exerts homologous tumor targeting and photothermal effects, inducing immunogenic cell death. Simultaneously, the sustained release of MOF@CM shows enhanced antigen presentation in dendritic cells (DCs) with the help of CpG, and induces DC maturation and activated immune responses, acting as an effective vaccine to prevent tumor recurrence. The platform harnesses the combined advantages of the local thermal effect and the presence of a Cu‐based MOF, which endow antibacterial properties and stimulate angiogenesis, thereby facilitating wound healing and mitigating radiation dermatitis. This integrated microsphere treatment platform represents a promising strategy for addressing melanoma. [ABSTRACT FROM AUTHOR]

Despite the recent wide investigation on active cancer drug delivery, there are still strong medical unmet needs for active tumor‐environment responsive cancer drug delivery in terms of spatiotemporal control. Herein, a biohybrid system of pH‐responsive peptide nanotubes (PNTs)‐coated microalgae for active cancer drug delivery in response to the tumor‐environment is developed. The amphiphilic PNTs are effectively used to encapsulate cancer drugs and coat the living microalgae of C. reinhardtii by electrostatic interactions. The drug‐loaded PNTs‐based biohybrid microalgae maintain agile movement with phototaxis behavior. After in vitro characterization and cytotoxicity assessment, it is shown that the biohybrid microalgae could be phototactically localized to the cancer cells and pH‐responsively disassembled to release cancer drugs in a controlled manner. Finally, with the encapsulation of paclitaxel, the statistically significant suppression of tumor growth in xenograft tumor model animals is successfully demonstrated. Taken together, the feasibility of the multifunctional microrobotic platform for advanced cancer therapy is confirmed.

Neutrophil extracellular traps (NETs) formed by neutrophils are netlike scaffolds that mainly contain DNA and a variety of granule proteins. Many stimuli can lead to the NET formation through independent molecular pathways. Clinically, the abundance of NETs is correlated with poor tumor prognosis. The biological actions of NETs are complex and diverse, including promoting tumor progression, awakening the dormant cancer cells, and resulting in immunosuppression in support of tumor growth and metastasis. Therefore, NET‐associated pathological processes provide an important clue for both diagnostic imaging and alternative therapies for many kinds of cancers. In recent years, scientists’ efforts have focused on developing novel imaging probes to visualize NETs and therapeutic strategies by degrading NETs or inhibiting its formation to block their pro‐tumoral functions. In this review, the development and evaluation of NETs‐targeted imaging and intervention progress for tumor therapy are focused on.

Immuno-oncology (IO) and targeted therapies, such as small molecule inhibitors, have changed the landscape of cancer treatment and prognosis; however, durable responses have been difficult to achieve due to tumor heterogeneity, development of drug resistance, and adverse effects that limit dosing and prolonged drug use. To improve upon the current medicinal armamentarium, there is an urgent need for new ways to understand, reverse, and treat carcinogenesis. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) 9 is a powerful and efficient tool for genome editing that has shown significant promise for developing new therapeutics. While CRISPR/Cas9 has been successfully used for pre-clinical cancer research, its use in the clinical setting is still in an early stage of development. The purpose of this review is to describe the CRISPR technology and to provide an overview of its current applications and future potential as cancer therapies.

Developing biocompatible material systems with accurate functional designability and powerful integration capability is the urgent demand of efficient cancer diagnosis and therapy. Deoxyribonucleic acids (DNAs) as biomacromolecules are characterized with sequence programmability, rich biological activity, and molecular recognition, and show great performance in the fabrication of biomedical materials. Rolling circle amplification (RCA) is an efficient isothermal enzymatic amplification strategy for production of ultralong single‐stranded DNA (ssDNA) with defined repeat sequences and structures. By virtue of rational design of the RCA templates sequences, the produced ssDNA enables to integrate and amplify the required function modules, which endows RCA‐based DNA materials with extraordinary performance in cancer therapeutics. In this review, RCA‐based strategies for integration of functional modules are systematically summarized; construction of RCA‐based functional DNA materials and their recent progress in cancer therapeutics including detection, bioimaging, and therapy are overviewed; and finally the opportunities and challenges of RCA‐based assembly strategy in terms of material construction and applications in cancer diagnosis and therapy are discussed. It is envisioned that RCA‐based DNA‐functional materials will provide typical paradigms for the application of DNA‐functional materials in the field of cancer therapeutics, and hopefully provide more possibilities for precision medicine. [ABSTRACT FROM AUTHOR]

Patients who undergo resection for melanoma face challenges, such as delayed healing and radiation dermatitis. Moreover, incomplete tumor resection is a key factor contributing to poor prognosis and increased recurrence rates. However, a therapeutic platform that can effectively prevent tumor recurrence and promote wound healing remains a challenge. Hence, a pioneering approach is presented using melanoma‐derived cancer cell membrane (CM) as a tumor antigen to encapsulate copper (Cu)‐based metal‐organic framework (MOF) nanomaterials to fabricate nanomaterials termed MOF@CM. Then MOF@CM is adsorbed onto polydopamine (PDA)‐modified poly lactic‐co‐glycolic acid (PLGA) porous microspheres (PLGA/PDA) to develop the copper nanomaterials‐decorated microspheres termed PLGA/PDA‐CCM (PLGA/PDA loaded with CM‐coated MOF). It exerts homologous tumor targeting and photothermal effects, inducing immunogenic cell death. Simultaneously, the sustained release of MOF@CM shows enhanced antigen presentation in dendritic cells (DCs) with the help of CpG, and induces DC maturation and activated immune responses, acting as an effective vaccine to prevent tumor recurrence. The platform harnesses the combined advantages of the local thermal effect and the presence of a Cu‐based MOF, which endow antibacterial properties and stimulate angiogenesis, thereby facilitating wound healing and mitigating radiation dermatitis. This integrated microsphere treatment platform represents a promising strategy for addressing melanoma.

Cancer immunotherapy using anti‐programmed death‐ligand 1 (PD‐L1) antibodies has been used in various clinical applications and achieved certain results. However, such limitations as autoimmunity, tumor hyperprogression, and overall low patient response rate impede its further clinical application. Mounting evidence has revealed that PD‐L1 is not only present in tumor cell membrane but also in cytoplasm, exosome, or even nucleus. Among these, the dynamic and spatial heterogeneous expression of PD‐L1 in tumors is mainly responsible for the unsatisfactory efficacy of PD‐L1 antibodies. Hence, numerous studies focus on inhibiting or degrading PD‐L1 to improve immune response, while a comprehensive understanding of the molecular mechanisms underlying spatial heterogeneity of PD‐L1 can fundamentally transform the current status of PD‐L1 antibodies in clinical development. Herein, the concept of spatial heterogeneous expression of PD‐L1 is creatively introduced, encompassing the structure and biological functions of various kinds of PD‐L1 (including mPD‐L1, cPD‐L1, nPD‐L1, and exoPD‐L1). Then an in‐depth analysis of the regulatory mechanisms and potential therapeutic targets of PD‐L1 is provided, seeking to offer a solid basis for future investigation. Moreover, the current status of agents is summarized, especially small molecular modulators development directed at these new targets, offering a novel perspective on potential PD‐L1 therapeutics strategies. [ABSTRACT FROM AUTHOR]

In recent years, with the continuous in-depth exploration of the molecular mechanisms of tumorigenesis, numerous potential new targets for cancer treatment have been identified, some of which have been further developed in clinical practice and have produced positive outcomes. Notably, researchers' initial motivation for studying copper metabolism in cancer stems from the fact that copper is a necessary trace element for organisms and is closely connected to body growth and metabolism. Moreover, over the past few decades, considerable progress has been made in understanding the molecular processes and correlations between copper and cancer. Certain achievements have been made in the development and use of relevant clinical medications. The concept of "cuproptosis," a novel concept that differs from previous forms of cell death, was first proposed by a group of scientists last year, offering fresh perspectives on the targeting capabilities of copper in the treatment of cancer. In this review, we introduced the fundamental physiological functions of copper, the key components of copper metabolism, and a summary of the current research contributions on the connection between copper and cancer. In addition, the development of new copper-based nanomaterials and their associated mechanisms of action are discussed. Finally, we described how the susceptibility of cancer cells to this metallic nutrition could be leveraged to further improve the existing cancer treatment paradigm in the new setting. [ABSTRACT FROM AUTHOR]

Developing biocompatible material systems with accurate functional designability and powerful integration capability is the urgent demand of efficient cancer diagnosis and therapy. Deoxyribonucleic acids (DNAs) as biomacromolecules are characterized with sequence programmability, rich biological activity, and molecular recognition, and show great performance in the fabrication of biomedical materials. Rolling circle amplification (RCA) is an efficient isothermal enzymatic amplification strategy for production of ultralong single‐stranded DNA (ssDNA) with defined repeat sequences and structures. By virtue of rational design of the RCA templates sequences, the produced ssDNA enables to integrate and amplify the required function modules, which endows RCA‐based DNA materials with extraordinary performance in cancer therapeutics. In this review, RCA‐based strategies for integration of functional modules are systematically summarized; construction of RCA‐based functional DNA materials and their recent progress in cancer therapeutics including detection, bioimaging, and therapy are overviewed; and finally the opportunities and challenges of RCA‐based assembly strategy in terms of material construction and applications in cancer diagnosis and therapy are discussed. It is envisioned that RCA‐based DNA‐functional materials will provide typical paradigms for the application of DNA‐functional materials in the field of cancer therapeutics, and hopefully provide more possibilities for precision medicine.

This article is an editorial published in Frontiers in Cell & Developmental Biology. It discusses the role of protein kinase inhibitors in neurodegeneration and cancer targeted therapies. The editorial highlights the importance of protein kinases in various cellular functions and their association with cancer development and neurodegenerative disorders. It explores the involvement of kinases in the initiation and progression of these conditions and suggests avenues for future research. The editorial also provides specific examples of protein kinases, such as p90 ribosomal S6 kinase, receptor tyrosine kinase-like orphan receptor 1, interleukin-1 receptor-associated kinase 4, activin receptor-like kinase 3, and putative markers in glioblastoma multiforme microenvironment. [Extracted from the article]

Abstract Background Cancer survival rates have been steadily improving in the adolescent and young adult (AYA) population, but survivors are at increased risk for cardiovascular disease (CVD). The cardiotoxic effects of anthracycline therapy have been well studied. However, the cardiovascular toxicity associated with newer therapies, such as the vascular endothelial growth factor (VEGF) inhibitors, is less well understood. Objective This retrospective study of AYA cancer survivors sought to gain insight into their burden of cardiovascular toxicities (CT) following initiation of anthracycline and/or VEGF inhibitor therapy. Methods Data were extracted from electronic medical records over a fourteen-year period at a single institution. Cox proportional hazards regression modeling was used to examine risk factors for CT within each treatment group. Cumulative incidence was calculated with death as a competing risk. Results Of the 1,165 AYA cancer survivors examined, 32%, 22%, and 34% of patients treated with anthracycline, VEGF inhibitor, or both, developed CT. Hypertension was the most common outcome reported. Males were at increased risk for CT following anthracycline therapy (HR: 1.34, 95% CI 1.04–1.73). The cumulative incidence of CT was highest in patients who received both anthracycline and VEGF inhibitor (50% at ten years of follow up). Conclusions CT was common among AYA cancer survivors who received anthracycline and/or VEGF inhibitor therapy. Male sex was an independent risk factor for CT following anthracycline treatment. Further screening and surveillance are warranted to continue understanding the burden of CVD following VEGF inhibitor therapy.

Cancer is an abnormal state of cells where they undergo uncontrolled proliferation and produce aggressive malignancies that causes millions of deaths every year. With the new understanding of the molecular mechanism(s) of disease progression, our knowledge about the disease is snowballing, leading to the evolution of many new therapeutic regimes and their successive trials. In the past few decades, various combinations of therapies have been proposed and are presently employed in the treatment of diverse cancers. Targeted drug therapy, immunotherapy, and personalized medicines are now largely being employed, which were not common a few years back. The field of cancer discoveries and therapeutics are evolving fast as cancer type-specific biomarkers are progressively being identified and several types of cancers are nowadays undergoing systematic therapies, extending patients' disease-free survival thereafter. Although growing evidence shows that a systematic and targeted approach could be the future of cancer medicine, chemotherapy remains a largely opted therapeutic option despite its known side effects on the patient's physical and psychological health. Chemotherapeutic agents/pharmaceuticals served a great purpose over the past few decades and have remained the frontline choice for advanced-stage malignancies where surgery and/or radiation therapy cannot be prescribed due to specific reasons. The present report succinctly reviews the existing and contemporary advancements in chemotherapy and assesses the status of the enrolled drugs/pharmaceuticals; it also comprehensively discusses the emerging role of specific/targeted therapeutic strategies that are presently being employed to achieve better clinical success/survival rate in cancer patients.

Abstract Cancer immunotherapy using anti‐programmed death‐ligand 1 (PD‐L1) antibodies has been used in various clinical applications and achieved certain results. However, such limitations as autoimmunity, tumor hyperprogression, and overall low patient response rate impede its further clinical application. Mounting evidence has revealed that PD‐L1 is not only present in tumor cell membrane but also in cytoplasm, exosome, or even nucleus. Among these, the dynamic and spatial heterogeneous expression of PD‐L1 in tumors is mainly responsible for the unsatisfactory efficacy of PD‐L1 antibodies. Hence, numerous studies focus on inhibiting or degrading PD‐L1 to improve immune response, while a comprehensive understanding of the molecular mechanisms underlying spatial heterogeneity of PD‐L1 can fundamentally transform the current status of PD‐L1 antibodies in clinical development. Herein, the concept of spatial heterogeneous expression of PD‐L1 is creatively introduced, encompassing the structure and biological functions of various kinds of PD‐L1 (including mPD‐L1, cPD‐L1, nPD‐L1, and exoPD‐L1). Then an in‐depth analysis of the regulatory mechanisms and potential therapeutic targets of PD‐L1 is provided, seeking to offer a solid basis for future investigation. Moreover, the current status of agents is summarized, especially small molecular modulators development directed at these new targets, offering a novel perspective on potential PD‐L1 therapeutics strategies.

The vascular microenvironment is the scale at which microvascular transport, interstitial tissue properties and cell metabolism interact. The vascular microenvironment has been widely studied by means of quantitative approaches, including multi‐physics mathematical models as it is a central system for the pathophysiology of many diseases, such as cancer. The microvascular architecture is a key factor for fluid balance and mass transfer in the vascular microenvironment, together with the physical parameters characterizing the vascular wall and the interstitial tissue. The scientific literature of this field has witnessed a long debate about which factor of this multifaceted system is the most relevant. The purpose of this work is to combine the interpretative power of an advanced multi‐physics model of the vascular microenvironment with state of the art and robust sensitivity analysis methods, in order to determine the factors that most significantly impact quantities of interest, related in particular to cancer treatment. We are particularly interested in comparing the factors related to the microvascular architecture with the ones affecting the physics of microvascular transport. Ultimately, this work will provide further insight into how the vascular microenvironment affects cancer therapies, such as chemotherapy, radiotherapy or immunotherapy. [ABSTRACT FROM AUTHOR]

Cellular response upon nsPEF exposure depends on different parameters, such as pulse number and duration, the intensity of the electric field, pulse repetition rate (PRR), pulsing buffer composition, absorbed energy, and local temperature increase. Therefore, a deep insight into the impact of such parameters on cellular response is paramount to adaptively optimize nsPEF treatment. Herein, we examined the effects of nsPEF ≤ 10 ns on long-term cellular viability and growth as a function of pulse duration (2–10 ns), PRR (20 and 200 Hz), cumulative time duration (1–5 µs), and absorbed electrical energy density (up to 81 mJ/mm3 in sucrose-containing low-conductivity buffer and up to 700 mJ/mm3 in high-conductivity HBSS buffer). Our results show that the effectiveness of nsPEFs in ablating 3D-grown cancer cells depends on the medium to which the cells are exposed and the PRR. When a medium with low-conductivity is used, the pulses do not result in cell ablation. Conversely, when the same pulse parameters are applied in a high-conductivity HBSS buffer and high PRRs are applied, the local temperature rises and yields either cell sensitization to nsPEFs or thermal damage. [ABSTRACT FROM AUTHOR]

BACKGROUND: There are limited data to guide oncology and cardiology decision-making in patients with a left ventricular assist device (LVAD) and concurrent active malignancy. OBJECTIVES: The goal of this study was to describe cancer treatment approaches, complications, and survival among patients with active cancer on LVAD support in 2 tertiary heart failure and oncology programs. METHODS: In this retrospective cohort study, LVAD databases were reviewed to identify patients with a cancer diagnosis at the time of or after LVAD implantation. We created a 3:1 matched cohort based on age, sex, etiology of cardiomyopathy, LVAD implant strategy, and INTERMACS profile stratified by site. Kaplan-Meier analysis and Cox proportional hazards models were used to compare survival between patients with cancer and non-cancer comparators. RESULTS: Among 1,123 patients who underwent LVAD implantation between 2005 and 2019, 22 patients with LVADs with active cancer and 66 matched non-cancer comparators were identified. Median age was 62 years (range 41 to 73 years); 50% of patients with cancer were African-American, and 27% were women. Prostate cancer, followed by renal cell cancer and hematologic malignancies were the most common diagnoses. There was no significant difference in unadjusted Kaplan-Meier median survival estimates from the time of LVAD placement between patients with cancer (3.53 years; 95% confidence interval [CI]: 1.41 to 5.33) and non-cancer comparators (3.03 years; 95% CI: 1.83 to 5.26; log-rank P = 0.99). In Cox proportional hazard models, cancer diagnosis as a time-varying variable was associated with a statistically significant increase in death (hazard ratio: 2.05; 95% CI: 1.03 to 4.12; P = 0.04). Patients with cancer had less gastrointestinal bleeding compared with matched non-cancer comparators (P = 0.016). Other complications were not significantly different. CONCLUSIONS: Our study provides initial feasibility and safety data and set a framework for multidisciplinary team management of patients with cancer and LVADs.

A study published in Critical Care Medicine explores the impact of delirium on cancer patients who are admitted to the intensive care unit (ICU). The study, conducted in Brazil, included patients with active cancer who experienced an unplanned ICU admission and were discharged alive from the hospital. The researchers found that ICU delirium was associated with a higher likelihood of changes in cancer treatment plans after discharge from the ICU. Delirium was also linked to a greater risk of functional dependence and increased mortality. The study highlights the need for efforts to prevent delirium in ICU patients, especially those with cancer. [Extracted from the article]

The development of new anticancer therapies tends to be very slow. Although their impact on potential candidates is confirmed in preclinical studies, ∼95 % of these new therapies are not approved when tested in clinical trials. One of the main reasons for this is the lack of accurate preclinical models. In this context, there are different patient-derived models, which have emerged as a powerful oncological tool: patient-derived xenografts (PDXs), patient-derived organoids (PDOs), and patient-derived cells (PDCs). Although all these models are widely applied, PDXs, which are created by engraftment of patient tumor tissues into mice, is considered more reliable. In fundamental research, the PDX model is used to evaluate drug-sensitive markers and, in clinical practice, to select a personalized therapeutic strategy. Melatonin is of particular importance in the development of innovative cancer treatments due to its oncostatic impact and lack of adverse effects. However, the literature regarding the oncostatic effect of melatonin in patient-derived tumor models is scant. This review aims to describe the important role of patient-derived models in the development of anticancer treatments, focusing, in particular, on PDX models, as well as their use in cancer research. This review also summarizes the existing literature on the anti-tumoral effect of melatonin in patient-derived models in order to propose future anti-neoplastic clinical applications.

The new era of nanomedicine offers significant opportunities for cancer diagnostics and treatment. Magnetic nanoplatforms could be highly effective tools for cancer diagnosis and treatment in the future. Due to their tunable morphologies and superior properties, multifunctional magnetic nanomaterials and their hybrid nanostructures can be designed as specific carriers of drugs, imaging agents, and magnetic theranostics. Multifunctional magnetic nanostructures are promising theranostic agents due to their ability to diagnose and combine therapies. This review provides a comprehensive overview of the development of advanced multifunctional magnetic nanostructures combining magnetic and optical properties, providing photoresponsive magnetic platforms for promising medical applications. Moreover, this review discusses various innovative developments using multifunctional magnetic nanostructures, including drug delivery, cancer treatment, tumor-specific ligands that deliver chemotherapeutics or hormonal agents, magnetic resonance imaging, and tissue engineering. Additionally, artificial intelligence (AI) can be used to optimize material properties in cancer diagnosis and treatment, based on predicted interactions with drugs, cell membranes, vasculature, biological fluid, and the immune system to enhance the effectiveness of therapeutic agents. Furthermore, this review provides an overview of AI approaches used to assess the practical utility of multifunctional magnetic nanostructures for cancer diagnosis and treatment. Finally, the review presents the current knowledge and perspectives on hybrid magnetic systems as cancer treatment tools with AI models. [ABSTRACT FROM AUTHOR]

Simple Summary: In the future, numbers of cancer survivors will increase due to early detection and new therapies, but it is important to consider the long-term consequences of disease and treatment. The purpose of this study is to assess the impact of cancer and treatment on the employment status of cancer survivors. Implementing a strict selection of articles to be analyzed, in order to mitigate the interference of publication and selection bias on the final results, we highlighted how cancer, treatments, and related disabilities are risk factors for unemployment. We believe that the negative influence of cancer on people's lives, including in terms of employment status with consequential fallout for morbidity and mortality, needs to be addressed by promoting health and social welfare support programs from diagnosis to follow-up, substantiating patient involvement in treatment choices. The purpose of our study is to examine whether cancer and treatments are associated with job loss or changes in employment status. Eight prospective studies were included in the systematic review and meta-analysis, with a population aged 18–65 years, analyzing treatment regimen and psychophysical and social status in post-cancer follow-up of at least 2 years. In the meta-analysis, a comparison was made between recovered unemployed cases and cases from a standard reference population. Results are summarized graphically using a forest plot. We showed that cancer and subsequent treatment are risk factors for unemployment with an overall relative risk of 7.24 (lnRR: 1.98, 95% CI: 1.32–2.63) or for change in employment status. Individuals undergoing chemotherapy and/or radiation treatment and those with brain and colorectal cancers are more likely to develop disabilities that negatively affect the risk of unemployment. Finally, variables such as low level education, female sex, older age, and being overweight before starting therapy are associated with higher risk of unemployment. In the future, it will be necessary for people with cancer to have access to specific health, social welfare, and employment support programs. In addition, it is desirable that they become more involved in their choice of therapeutic treatment. [ABSTRACT FROM AUTHOR]

Inspired by endogenous physiological electric fields in humans, electricity has been widely used as an accessible source of physical stimulation to help treat diseases, including cancer therapy. Electricity can not only be used as a weapon to directly kill cancer cells but also be used as a “switch” to control the anticancer drug delivery systems (DDSs), enabling on‐demand drug release at the lesion sites. Recently, the antitumor electrotherapy based on the induction of tumor cell apoptosis by highly toxic reactive oxygen species (ROS) has been developed. Many studies have proved that the electrical stimulation can mobilize the body's immune system to kill tumors through different mechanisms. When the single electrical therapy is not effective for the treatment of advanced tumors, the integration with immunotherapy is considered as “life‐saving straw.” Moreover, with the growing need for convenient, personalized, and telehealth care and treatment, the emerging nanotechnologies such as self‐powered triboelectric nanogenerators (TENGs) are integrated with electrotherapy. This review comprehensively summarizes these developments from clinic applications to new emerging strategies and proposes future challenges and opportunities in this field.

Simple Summary: DNA damage response (DDR)-related proteins contribute to tumorigenesis, tumor progression, and drug resistance. Pharmacological inhibition of DDR-related proteins, such as checkpoint kinase 1 (Chk1), exerts antitumor effects but has serious side effects. Therefore, we attempted to specifically kill cancer cells with low concentrations of drugs by simultaneously inhibiting two DDR-related proteins. In this study, we demonstrated that the combined treatment with ataxia telangiectasia-mutated serine/threonine kinase (ATM) inhibitor (ATMi) and Chk1 inhibitor (Chk1i) exerts synergistic antitumor effects and induces cancer-specific synthetic lethality at low doses. The ATMi and Chk1i combination synergistically promotes CDK1 activation, resulting in the induction of apoptosis with enhanced cell cycle progression in cancer cells. Considering that the combined treatment exerts antitumor effects at one-tenth the concentrations described in previous reports, with high antitumor efficacy and few side effects it could be an effective treatment approach. Genetic abnormalities induce the DNA damage response (DDR), which enables DNA repair at cell cycle checkpoints. Although the DDR is thought to function in preventing the onset and progression of cancer, DDR-related proteins are also thought to contribute to tumorigenesis, tumor progression, and drug resistance by preventing irreparable genomic abnormalities from inducing cell death. In the present study, the combination of ataxia telangiectasia-mutated serine/threonine kinase (ATM) and checkpoint kinase 1 (Chk1) inhibition exhibited synergistic antitumor effects and induced synergistic lethality in colorectal cancer cells at a low dose. The ATM and Chk1 inhibitors synergistically promoted the activation of cyclin-dependent kinase 1 by decreasing the phosphorylation levels of T14 and Y15. Furthermore, the combined treatment increased the number of sub-G1-stage cells, phospho-histone H2A.X-positive cells, and TdT-mediated dUTP nick-end labeling-positive cells among colon cancer cells, suggesting that the therapy induces apoptosis. Finally, the combined treatment exhibited a robust antitumor activity in syngeneic tumor model mice. These findings should contribute to the development of new treatments for colorectal cancer that directly exploit the genomic instability of cancer cells. [ABSTRACT FROM AUTHOR]

Exosomes are biological nanoscale spherical lipid bilayer vesicles, 40–160 nm in diameter, produced by most mammalian cells in both physiological and pathological conditions. Exosomes are formed via the endosomal sorting complex required for transport (ESCRT). The primary function of exosomes is mediating cell-to-cell communication. In terms of cancer, exosomes play important roles as mediators of intercellular communication, leading to tumor progression. Moreover, they can serve as biomarkers for cancer detection and progression. Therefore, their utilization in cancer therapies has been suggested, either as drug delivery carriers or as a diagnostic tool. However, exosomes were also reported to be involved in cancer drug resistance via transferring information of drug resistance to sensitive cells. It is important to consider the current knowledge regarding the role of exosomes in cancer, drug resistance, cancer therapies, and their clinical application in cancer therapies. [ABSTRACT FROM AUTHOR]

Micro/nanorobots (MNRs) are capable of autonomous motion, breaking through the limitations of traditional passive transport of nanocarriers. Among them, chemically driven MNRs are the earliest MNRs studied and have received extensive attention from researchers. This review first focuses on the material properties, preparation, driving forms, and mechanisms of chemically driven MNRs. The current status of research on chemically driven MNRs in biomedicine is summarized for various biological applications (drug delivery, diagnostics, anti‐inflammatory, antibacterial, and disease treatment). In terms of biosafety, possible safety issues are analyzed in the context of chemically driven microrobotic applications in terms of three aspects: component characteristics, chemical engines and biological environment. Finally, the challenges and possible future directions of chemically driven MNRs are presented. [ABSTRACT FROM AUTHOR]

Recent years have witnessed the rapid development of the biomimetic nanotechnology regarding the use of certain components (such as cell membranes, extracellular vesicles, proteins, etc.) derived from different cells to fabricate nanoparticles (NPs) for cancer treatment. These biomimetic NPs usually inherit certain abilities from their parental cells, such as long blood circulation, capacity to escape from mononuclear phagocytic system, active tumor‐targeting, and controlled drug release. Immunocytes play vital roles in different tumor progression stages, and can quickly and accurately react to tumor progression via specific targeting and immune surveillance. Therefore, increasing studies focus on constructing biomimetic NPs with components isolated from immunocytes. This review introduces four main types of immunocyte‐derived nanodrugs—membrane‐coated NPs, exosomes or extracellular vesicles, functional protein‐incorporated NPs, and exosome mimetics—and summarizes the recent advances of these nanodrugs for cancer therapy. Some current challenges and future research directions of immunocyte‐derived nanodrugs are also proposed. It is hoped that this review may help researchers in the related field to design new immunocyte‐derived nanomedicines and promote their preclinical and clinical applications in the near future. [ABSTRACT FROM AUTHOR]

Targeting the distinct metabolic needs of tumor cells has recently emerged as a promising strategy for cancer therapy. The heterogeneous, context-dependent nature of cancer cell metabolism, however, poses challenges to identifying effective therapeutic interventions. Here, we utilize various unsupervised and supervised multivariate modeling approaches to systematically pinpoint recurrent metabolic states within hundreds of cancer cell lines, elucidate their association with tumor lineage and growth environments, and uncover vulnerabilities linked to their metabolic states across diverse genetic and tissue contexts. We validate key findings via analysis of data from patient-derived tumors and pharmacological screens and by performing genetic and pharmacological experiments. Our analysis uncovers synthetically lethal associations between the tumor metabolic state (e.g., oxidative phosphorylation), driver mutations (e.g., loss of tumor suppressor PTEN), and actionable biological targets (e.g., mitochondrial electron transport chain). Investigating the mechanisms underlying these relationships can inform the development of more precise and context-specific, metabolism-targeted cancer therapies. [Display omitted] • Most metabolic pathway heterogeneities are cancer type specific; Oxphos variability is not • OxphosHigh and OxphosLow states show unique vulnerabilities independent of growth condition • PTEN loss increases OxphosHigh state's dependency on mitochondrial electron transport chain • Oxphos inhibitors show higher potency in PTENNull glioma cells than in PTEN-expressing cells Abecunas et al. use multivariate modeling to explore recurrent metabolic states in cancer cells and uncover synthetically lethal interactions across diverse metabolic, oncogenic, and tissue contexts. They validate key findings via independent data analysis and new experiments. They find that PTEN loss predicts increased dependency on mitochondrial respiratory chain in OxphosHigh tumor cells. [ABSTRACT FROM AUTHOR]

Cellular response upon nsPEF exposure depends on different parameters, such as pulse number and duration, the intensity of the electric field, pulse repetition rate (PRR), pulsing buffer composition, absorbed energy, and local temperature increase. Therefore, a deep insight into the impact of such parameters on cellular response is paramount to adaptively optimize nsPEF treatment. Herein, we examined the effects of nsPEF ≤ 10 ns on long-term cellular viability and growth as a function of pulse duration (2–10 ns), PRR (20 and 200 Hz), cumulative time duration (1–5 µs), and absorbed electrical energy density (up to 81 mJ/mm3 in sucrose-containing low-conductivity buffer and up to 700 mJ/mm3 in high-conductivity HBSS buffer). Our results show that the effectiveness of nsPEFs in ablating 3D-grown cancer cells depends on the medium to which the cells are exposed and the PRR. When a medium with low-conductivity is used, the pulses do not result in cell ablation. Conversely, when the same pulse parameters are applied in a high-conductivity HBSS buffer and high PRRs are applied, the local temperature rises and yields either cell sensitization to nsPEFs or thermal damage.

Lanthanide‐doped upconversion nanoparticles (UCNPs) are anti‐Stokes emitters, which can produce higher‐energy ultraviolet/visible and near‐infrared (NIR) luminescence when excited with low‐energy NIR light. They are featured with nonphotobleaching, sharp emission peaks, superstability, low toxicity, low imaging background, and functional multimodality. These characteristics endow them to be useful as nanoprobes for diagnostic applications and imaging‐guided cancer therapy. Importantly, the ability to convert tissue‐penetrating NIR light into visible and ultraviolet range can expedite Fenton‐ or Fenton‐based processes in chemical dynamic therapy (CDT), activate photosensitizers (PSs) to produce singlet oxygen in photodynamic therapy (PDT), and regulate light‐controlled drug delivery processes for efficacious cancer therapy. The past decade witnessed fast progress of UCNPs as agents in single‐mode therapy or combined therapies in the forefront researches on fighting cancer. This review summarizes the fundamental roles of UCNPs in cancer therapy, highlights types of cell deaths induced by excessive reactive oxygen species (ROS), and showcases cutting‐edge applications in combined cancer therapies as well as imaging‐guided cancer therapy. Challenges and outlook on the use of UCNPs for future directions in cancer therapy are also discussed.

Cancer is one of the leading global causes of death in both men and women. Colorectal cancer (CRC) alone accounts for ∼10 % of total new global cases and poses an over 4% lifetime risk of developing cancer. Recent advancements in the field of biotechnology and microbiology concocted novel microbe-based therapies to treat various cancers, including CRC. Microbes have been explored for human use since centuries, especially for the treatment of various ailments. The utility of microbes in cancer therapeutics is widely explored, and various bacteria, fungi, and viruses are currently in use for the development of cancer therapeutics. The human gut hosts about 100 trillion microbes that release their metabolites in active, inactive, or dead conditions. Microbial secondary metabolites, proteins, immunotoxins, and enzymes are used to target cancer cells to induce cell cycle arrest, apoptosis, and death. Various approaches, such as dietary interventions, the use of prebiotics and probiotics, and fecal microbiota transplantation have been used to modulate the gut microbiota in order to prevent or treat CRC pathogenesis. The present review highlights the role of the gut microbiota in CRC precipitation, the potential mechanisms and use of microorganisms as CRC biomarkers, and strategies to modulate microbiota for the prevention and treatment of CRC. [ABSTRACT FROM AUTHOR]

Simple Summary: Coronavirus disease 2019 (COVID-19) is the greatest present-day public and global health challenge, and patients with cancer are especially vulnerable, emphasizing the importance of vaccination. However, little is known about the effects of cancer and treatment on vaccine effectiveness and its safety. The aim of this review is to explore current literature regarding the immune response rate and safety profile of COVID-19 vaccination in patients with solid and hematologic cancers and those receiving various forms of treatment. Immune response rates were described to be lower amongst cancer patients, especially those with hematologic cancers, and those receiving chemotherapy, radiotherapy, or immunosuppressants. Nevertheless, sufficient immune response was still generated in many patients, and vaccination was overall described to be safe and well-tolerated, therefore supporting vaccine encouragement. Few guidelines exist for COVID-19 vaccination amongst cancer patients, fostering uncertainty regarding the immunogenicity, safety, and effects of cancer therapies on vaccination, which this review aims to address. A literature review was conducted to include the latest articles covering the immunogenicity and safety of COVID-19 vaccination in patients with solid and hematologic cancers receiving various treatments. Lower seropositivity following vaccination was associated with malignancy (compared to the general population), and hematologic malignancy (compared to solid cancers). Patients receiving active cancer therapy (unspecified), chemotherapy, radiotherapy, and immunosuppressants generally demonstrated lower seropositivity compared to healthy controls; though checkpoint inhibition, endocrine therapy, and cyclin dependent kinase inhibition did not appear to affect seropositivity. Vaccination appeared safe and well-tolerated in patients with current or past cancer and those undergoing treatment. Adverse events were comparable to the general population, but inflammatory lymphadenopathy following vaccination was commonly reported and may be mistaken for malignant etiology. Additionally, radiation recall phenomenon was sporadically reported in patients who had received radiotherapy. Overall, while seropositivity rates were decreased, cancer patients showed capacity to generate safe and effective immune responses to COVID-19 vaccination, thus vaccination should be encouraged and hesitancy should be addressed in this population. [ABSTRACT FROM AUTHOR]

Engineered nanozymes have been developed to catalyze the production of reactive oxygen species (ROS) for cancer therapy, but currently, the ROS generation efficiency is still far from optimistic. In this study, a human self‐driven electrical stimulation enhanced catalytic system based on wearable triboelectric nanogenerator (TENG) and fully π‐conjugated covalent organic framework nanocages (hCOF) for improving cancer therapy is created. The fully π‐conjugated hCOF nanocage with high electron mobility under the self‐generated electric field can not only rearrange the local electric field for optimizing energy utilization, but also facilitates the access of electrolytes to optimize the utilization of the electric field. With the self‐powered wearable TENG, the peroxidase‐like activity of hCOF increased by 2.44‐fold and has electricity‐responsive doxorubicin delivery capacity for enhancing the therapeutic outcomes. The high‐efficient self‐driven electrical stimulation enhanced nanocatalytic system provides a new optimized model for the catalytic energy supply of nanozymes. [ABSTRACT FROM AUTHOR]

With the rapid progress in nanomaterials and biochemistry, there has been an explosion of interest in biomolecule‐modified quantum dots (QDs) for biomedical applications. Metal chalcogenide quantum dots (MCQDs), as the most widely studied QDs, have attracted tremendous attention in the biomedical field on account of their unique and excellent optical properties and the ease of biomolecular modifications. Herein, important advances in MCQDs over recent years are reviewed, from materials design to biomedical applications. Especially, this review focuses on the challenges encountered in the applications of MCQDs in biomedical fields and how these problems can be solved by rational design of synthesis methods and modifications, which have opened a universal route to develop the functionalized MCQDs. Moreover, recent processes in bioimaging, biosensing, and cancer therapy based on MCQDs are examined, including the rapid detection and diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). This review provides broad insights into MCQDs in the biomedical field and will inspire material researchers to develop MCQDs in the future. [ABSTRACT FROM AUTHOR]

Nanoparticle-based therapy has gained much attention in the pharmaceutical industry. Fucoidan is a sulfated polysaccharide naturally derived from marine brown algae and is widely used for medical applications. We explore preparation of fucoidan-based nanoparticles and their biomedical applications in the current review. The fucoidan-based nanoparticles have been synthesized using microwave, emulsion, solvent evaporation, green synthesis, polyelectrolyte self-assembly, precipitation, and ultrasonication methods. The synthesized nanoparticles have particle sizes ranging from 100 to 400 nm. Therefore, fucoidan-based nanoparticles have a variety of potential therapeutic applications, including drug delivery, cancer therapies, tissue engineering, antimicrobial applications, magnetic resonance imaging contrast, and atherothrombosis imaging. For example, fucoidan nanoparticles have been used to deliver curcumin, dextran, gentamicin, epigallocatechin gallate, and cisplatin for cancer therapies. Furthermore, fucoidan nanoparticles coupled with metal nanoparticles have been used to target and recognize clinical conditions for diagnostic purposes. Hence, fucoidan-based nanoparticles have been helpful for biomedical applications. [Display omitted] [ABSTRACT FROM AUTHOR]

G protein‐coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence‐specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor‐xenografted mouse models and patient‐derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin‐angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation. [ABSTRACT FROM AUTHOR]

Abstract G protein‐coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence‐specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor‐xenografted mouse models and patient‐derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin‐angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation.

The global cancer cases and mortality rates are increasing and demand efficient biomarkers for accurate screening, detection, diagnosis, and prognosis. Recent studies have demonstrated that variations in epigenetic mechanisms like aberrant promoter methylation, altered histone modification and mutations in ATP-dependent chromatin remodelling complexes play an important role in the development of carcinogenic events. However, the influence of other epigenetic alterations in various cancers was confirmed with evolving research and the emergence of high throughput technologies. Therefore, alterations in epigenetic marks may have clinical utility as potential biomarkers for early cancer detection and diagnosis. In this review, an outline of the key epigenetic mechanism(s), and their deregulation in cancer etiology have been discussed to decipher the future prospects in cancer therapeutics including precision medicine. Also, this review attempts to highlight the gaps in epigenetic drug development with emphasis on integrative analysis of epigenetic biomarkers to establish minimally noninvasive biomarkers with clinical applications. [ABSTRACT FROM AUTHOR]