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DNA Methylation Cancer Biomarkers: Translation to the Clinic.

Carcinogenesis is accompanied by widespread DNA methylation changes within the cell. These changes are characterized by a globally hypomethylated genome with focal hypermethylation of numerous 5'-cytosine-phosphate-guanine-3' (CpG) islands, often spanning gene promoters and first exons. Many of these epigenetic changes occur early in tumorigenesis and are highly pervasive across a tumor type. This allows DNA methylation cancer biomarkers to be suitable for early detection and also to have utility across a range of areas relevant to cancer detection and treatment. Such tests are also simple in

From monoclonals to bispecific T cell engagers: the evolving antibody-based therapy landscape in acute myeloid leukemia.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with a poor prognosis despite advances in treatment strategies. Standard treatment regimens induce remissions in many patients, but relapse occurs in approximately half, highlighting the urgent need for novel therapeutic strategies. Antibody-based therapies have significantly improved the treatment of acute lymphoblastic leukemia (ALL), but progress in AML has been slower, with only gemtuzumab ozogamicin (GO) receiving FDA approval to date. This is largely due to the absence of AML-specific surface antigens and the challeng

Протеазомное ингибирование подрывает микроваскулярную целостность, оказывая заметное воздействие на неиммунные эндотелиальные клетки и иммунные клетки.

Для нескольких миеломы (ММ) установлены хемапаутические протеасомные ингибиторы Бортезомиб (БЗ, обратимый ингибитор) и Карфилзомиб (КФЗ, необратимый ингибитор). Вместе с тем, их целевые и нецелевые эффекты, связанные с прохожими в крови, точно не известны. Чтобы прояснить острое негативное воздействие внутривенного протеасомального ингибитора, мы изучили некоторые из ключевых типов микроваскулатуры крови: барьер эндотелиальные клетки, периферийные моноядерно-кротовые клетки крови и множественные клетки миеломы (MM1.S). BTZ, но не CFZ, является цитотоксичным для микровакулярных эндотелиальных к

Senescent immune cells in the tumor microenvironment: emerging insights into cancer immunotherapy resistance.

Cancer remains a leading cause of mortality worldwide, with rising incidence and death rates continuing to rise. While conventional treatments such as surgery, radiotherapy, and chemotherapy form the backbone of cancer care, they are often limited by adverse effects, recurrence risk, and incomplete tumor eradication. Tumor immunotherapy-particularly immune checkpoint inhibitors and chimeric antigen receptor (CAR) T cell therapy-has emerged as a transformative approach by activating and reprogramming anti-tumor immune responses. Despite these advances, significant challenges persist, including

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… For example, platinum-based chemotherapies are known to induce cardiotoxicity and nephrotoxicity, while other agents may cause peripheral neuropathy and a range of gastrointestinal complications ( 7 ). …

Novel Therapeutic Approaches in Pediatric Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common pediatric malignancy, characterized by the clonal proliferation of immature lymphoid precursors. The distinction between B-cell ALL (B-ALL) and T-cell ALL (T-ALL) is fundamental, as each subtype exhibits distinct cytomorphological, genetic, and clinical features influencing prognosis and therapeutic strategies. Conventional multi-phase chemotherapy has significantly improved survival rates, yet its efficacy is limited by severe short- and long-term toxicities, highlighting the need for more selective therapeutic approaches. Advances in mole

Novel Strategies for Tumor Treatment: Harnessing ROS-Inducing Active Ingredients from Traditional Chinese Medicine Through Multifunctional Nanoformulations.

Reactive oxygen species (ROS) encompass a diverse group of chemically reactive molecules or ions distinguished by their substantial oxidative potential. Empirical studies have shown that the targeted administration of high toxic concentrations of ROS can effectively induce tumor cell death in various types. Numerous bioactive ingredients derived from traditional Chinese medicine (TCM), recognized for their ROS-inducing properties, have demonstrated significant anti-tumor activity. Nonetheless, their clinical application has been hindered by challenges such as low solubility, limited bioavailab

A Comprehensive Review of Immunotherapy Clinical Trials for Metastatic Urothelial Carcinoma: Immune Checkpoint Inhibitors Alone or in Combination, Novel Antibodies, Cellular Therapies, and Vaccines.

Urothelial cancer is an immune-responsive cancer, but only a subset of patients benefits from immune checkpoint inhibition. Currently, single-agent immune checkpoint inhibitors (ICIs) and the combination of pembrolizumab with the antibody-drug conjugate enfortumab vedotin are approved to treat patients with metastatic UC (mUC). Approval of first-line nivolumab in combination with gemcitabine and cisplatin is expected imminently. Many treatment approaches are being investigated to better harness the immune system to fight mUC. In this review, we summarize the landmark clinical trials of ICIs th

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… A single-arm phase 2 trial of trastuzumab added to paclitaxel, carboplatin, and gemcitabine (PCG) chemotherapy had a 57% confirmed ORR but had higher than expected cardiotoxicity and has not been compared to PCG chemotherapy in a randomized trial [ 83 ]. …

Management of Potential Organ Donor: Indian Society of Critical Care Medicine-Position Statement.

This position statement is documented based on the input from all contributing coauthors from the Indian Society of Critical Care Medicine (ISCCM), following a comprehensive literature review and summary of current scientific evidence. Its objective is to provide the standard perspective for the management of potential organ/tissue donors after brain death (BD) in adults only, regardless of the availability of technology. This document should only be used for guidance only and is not a substitute for proper clinical decision making in particular circumstances of any case. Endorsement by the IS

A Clinical Viewpoint on the Use of Targeted Therapy in Advanced Gastric Cancer.

The development of therapies for advanced gastric cancer (GC) has made significant progress over the past few years. The identification of new molecules and molecular targets is expanding our understanding of the disease's intricate nature. The end of the classical oncology era, which relied on well-studied chemotherapeutic agents, is giving rise to novel and unexplored challenges, which will cause a significant transformation of the current oncological knowledge in the next few years. The integration of established clinically effective regimens in additional studies will be crucial in managin

Trial watch: beta-blockers in cancer therapy.

Compelling evidence supports the hypothesis that stress negatively impacts cancer development and prognosis. Irrespective of its physical, biological or psychological source, stress triggers a physiological response that is mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic adrenal medullary axis. The resulting release of glucocorticoids and catecholamines into the systemic circulation leads to neuroendocrine and metabolic adaptations that can affect immune homeostasis and immunosurveillance, thus impairing the detection and eradication of malignant cells. Moreover, catech

The role of exercise for pain management in adults living with and beyond cancer: a systematic review and meta-analysis.

BackgroundPain is a common side effect of cancer or cancer treatment that negatively impacts biopsychosocial wellbeing and quality of life. Exercise is a potential intervention to manage pain that is safe and has multiple benefits. The objective was to determine the role of exercise in cancer pain management.MethodsWe completed a systematic review and meta-analysis of exercise interventions in adults with any type or stage of cancer by searching Ovid MEDLINE®, Embase, APA PsycInfo, the Cochrane Central Register of Controlled Trials, CINAHL, and SPORTDiscus. We included experimental and quasi-e

MYCN Impact on High-Risk Neuroblastoma: From Diagnosis and Prognosis to Targeted Treatment.

Among childhood cancers, neuroblastoma is the most diffuse solid tumor and the deadliest in children. While to date, the pathology has become progressively manageable with a significant increase in 5-year survival for its less aggressive form, high-risk neuroblastoma (HR-NB) remains a major issue with poor outcome and little survivability of patients. The staging system has also been improved to better fit patient needs and to administer therapies in a more focused manner in consideration of pathology features. New and improved therapies have been developed; nevertheless, low efficacy and high

Is stroke incidence increased in survivors of adult cancers? A systematic review and meta-analysis.

PurposeExisting research hints that people living with and beyond cancer are at an increased risk of stroke. However, there is insufficient evidence to appropriately inform guidelines for specific stroke prevention or management for cancer patients. We conducted a systematic review and meta-analysis to describe and quantify stroke incidence in people living with and beyond cancer.MethodsMedline, CINAHL, and EMBASE were searched for epidemiological studies comparing stroke incidence between cancer and non-cancer patients. Reviewers independently extracted data; random-effects meta-analyses and

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… Individuals with cancer may suffer strokes caused by mechanisms related to malignancy-associated prothrombotic states including changes in platelet function and increased production of neutrophil elastase traps (NETs); cardiotoxicity-associated with chemotherapeutic and radiotherapy treatments; shared …

Translational Strategies to Target Metastatic Bone Disease.

Metastatic bone disease is a common and devastating complication to cancer, confounding treatments and recovery efforts and presenting a significant barrier to de-escalating the adverse outcomes associated with disease progression. Despite significant advances in the field, bone metastases remain presently incurable and contribute heavily to cancer-associated morbidity and mortality. Mechanisms associated with metastatic bone disease perpetuation and paralleled disruption of bone remodeling are highlighted to convey how they provide the foundation for therapeutic targets to stem disease escala

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… Myopathies are emerging beyond skeletal muscle weakness, as cardiotoxicity is often reported. 4. Modeling, Imaging, and Detection of Skeletal Metastases 4.1. …

Advances in Anti-Cancer Immunotherapy: Car-T Cell, Checkpoint Inhibitors, Dendritic Cell Vaccines, and Oncolytic Viruses, and Emerging Cellular and Molecular Targets.

Unlike traditional cancer therapies, such as surgery, radiation and chemotherapy that are typically non-specific, cancer immunotherapy harnesses the high specificity of a patient's own immune system to selectively kill cancer cells. The immune system is the body's main cancer surveillance system, but cancers may evade destruction thanks to various immune-suppressing mechanisms. We therefore need to deploy various immunotherapy-based strategies to help bolster the anti-tumour immune responses. These include engineering T cells to express chimeric antigen receptors (CARs) to specifically recogni

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… Although in clinics, anti-PD-1/PD-L1 therapies pose a number of adverse effects and toxicities such a cardiotoxicity, myocarditis, hepatitis, diarrhoea, endocrine dysfunction, etc., reviewed elsewhere [ 79 , 80 ]. …

Advances in Drug Delivery and Biomaterials: Facts and Vision.

Drug delivery and biomaterials are different fields of science but, at the same time, are tightly related and intertwined. The 2018 CRS Italy Chapter Annual Workshop aims to explore recent advances in design and development in these areas. Many colleagues from Europe participated to the Workshop, stimulating the discussion. To foster the discussion on recent research and networking opportunities, especially among younger attendees, all poster-presenting authors were asked to provide a short talk. The very friendly and stimulating atmosphere allowed the attendees to explore new frontiers and ta

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… Used in the majority of chemotherapies, DOXO is renowned for its extensive side-effect profile, in particular the dose-dependent cardiotoxicity, the lack of selectivity for tumor cells and the induced cell resistance. …

Epigenetic Dysregulation in Neurodegeneration: The Role of Histone Deacetylases and Emerging Inhibitor Strategies.

Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD) are characterized by complex pathologies with progressive neurodegeneration, protein misfolding, oxidative stress, and persistent inflammation. Recent findings indicate the pivotal involvement of epigenetic disruption, particularly aberrant histone deacetylase (HDAC) activity, in disease initiation and progression. In the current review, we systematically discuss the mechanistic function of HDACs across all classes (I, IIa, IIb, III, and IV) in neurodegenerative disease mechanis

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… Compound 4 demonstrated strong selectivity for HDAC6 (IC 50 = 0.26 μM) over HDAC1 and HDAC4, along with a low risk of cardiotoxicity (hERG IC 50 = 106 μM). …

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

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… Peng K., Zeng C., Gao Y., et al., “Overexpressed SIRT6 Ameliorates Doxorubicin‐induced Cardiotoxicity and Potentiates the Therapeutic Efficacy Through Metabolic Remodeling,” Acta Pharmaceutica Sinica B 13, no. 6 (2023): 2680–2700. 49. …

Exosomes in oncofertility: emerging roles in chemotherapy-induced reproductive damage and fertility preservation.

ABSTRACT: Oncofertility has emerged as a critical interdisciplinary field addressing the reproductive challenges faced by cancer patients, particularly those undergoing chemotherapy. While chemotherapeutic agents remain indispensable in cancer therapy, their gonadotoxic effects frequently result in diminished ovarian reserve, impaired spermatogenesis, and long-term infertility. Exosomes - small extracellular vesicles enriched with nucleic acids, proteins, and lipids - are increasingly recognized as key mediators of intercellular communication in both pathological and regenerative contexts. Rec

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… However, the expanding population of survivors faces long-term adverse effects of chemotherapy, including neurocognitive impairment, cardiotoxicity, secondary malignancies, and notably, gonadotoxicity, which threatens fertility, endocrine function, and quality of life ( Silva et al. 2018 ). …

Blockage of Autophagy for Cancer Therapy: A Comprehensive Review.

The incidence and mortality of cancer are increasing, making it a leading cause of death worldwide. Conventional treatments such as surgery, radiotherapy, and chemotherapy face significant limitations due to therapeutic resistance. Autophagy, a cellular self-degradation mechanism, plays a crucial role in cancer development, drug resistance, and treatment. This review investigates the potential of autophagy inhibition as a therapeutic strategy for cancer. A systematic search was conducted on Embase, PubMed, and Google Scholar databases from 1967 to 2024 to identify studies on autophagy inhibito