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Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.

Metastatic dissemination of solid tumors, a leading cause of cancer-related mortality, underscores the urgent need for enhanced insights into the molecular and cellular mechanisms underlying metastasis, chemoresistance, and the mechanistic backgrounds of individuals whose cancers are prone to migration. The most prevalent signaling cascade governed by multi-kinase inhibitors is the mitogen-activated protein kinase (MAPK) pathway, encompassing the RAS-RAF-MAPK kinase (MEK)-extracellular signal-related kinase (ERK) pathway. RAF kinase is a primary mediator of the MAPK pathway, responsible for th

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… In addition, RAF regulates checkpoint kinase 2 (CHK2) activity during cell cycle progression. …

Sexual dimorphism in cancer: molecular mechanisms and precision oncology perspectives.

Sex differences play a crucial role in determining tumor incidence, treatment sensitivity, and prognosis among men and women. However, current clinical cancer treatment strategies fail to account for these differences. Furthermore, the underlying mechanisms of tumor disparities between sexes remain elusive. Sex differences in sex chromosomes, hormone levels, metabolism, and immunity synergistically contribute to tumor-related disparities. As the demand for precision medicine escalates, there is an urgent need to conduct further exploration and research to address the tumor differences between

Advances and Hurdles in CAR T Cell Immune Therapy for Solid Tumors.

Chimeric antigen receptor (CAR) T cells in solid tumors have so far yielded limited results, in terms of therapeutic effects, as compared to the dramatic results observed for hematological malignancies. Many factors involve both the tumor cells and the microenvironment. The lack of specific target antigens and severe, potentially fatal, toxicities caused by on-target off-tumor toxicities constitute major hurdles. Furthermore, the tumor microenvironment is usually characterized by chronic inflammation, the presence of immunosuppressive molecules, and immune cells that can reduce CAR T cell effi

Interleukins in cancer: from biology to therapy.

Interleukins and associated cytokines serve as the means of communication for innate and adaptive immune cells as well as non-immune cells and tissues. Thus, interleukins have a critical role in cancer development, progression and control. Interleukins can nurture an environment enabling and favouring cancer growth while simultaneously being essential for a productive tumour-directed immune response. These properties of interleukins can be exploited to improve immunotherapies to promote effectiveness as well as to limit side effects. This Review aims to unravel some of these complex interactio

Therapeutic outcome of early-phase clinical trials in multiple myeloma: a meta-analysis.

Great progress in the treatment of patients with multiple myeloma (MM) has been made due to the development of novel drugs. Patients with relapsed/refractory MM (RRMM) can be enrolled in early-phase clinical trials, but their performance across the last decade is unknown. We conducted a meta-analysis on the overall response rate (ORR) and toxicity. PubMed, Embase, and Cochrane Library were systematically searched for phase I and phase II trials investigating an experimental compound as a single agent or in combination with dexamethasone, published from January 1, 2010 to July 1, 2020. Eighty-e

Cardio-Oncology Rehabilitation-Present and Future Perspectives.

Recent advances in cancer therapy have led to increased survival rates for cancer patients, but also allowed cardiovascular complications to become increasingly evident, with more than 40% of cancer deaths now being attributed to cardiovascular diseases. Cardiotoxicity is the most concerning cardiovascular complication, one caused mainly due to anti-cancer drugs. Among the harmful mechanisms of these drugs are DNA damage, endothelial dysfunction, and oxidative stress. Cancer patients can suffer reduced cardiorespiratory fitness as a secondary effect of anti-cancer therapies, tumor burden, and

Adding recombinant AAVs to the cancer therapeutics mix.

Gene therapy is a powerful biological tool that is reshaping therapeutic landscapes for several diseases. Researchers are using both non-viral and viral-based gene therapy methods with success in the lab and the clinic. In the cancer biology field, gene therapies are expanding treatment options and the possibility of favorable outcomes for patients. While cellular immunotherapies and oncolytic virotherapies have paved the way in cancer treatments based on genetic engineering, recombinant adeno-associated virus (rAAV), a viral-based module, is also emerging as a potential cancer therapeutic thr

Cancer Stem Cells (CSCs), Circulating Tumor Cells (CTCs) and Their Interplay with Cancer Associated Fibroblasts (CAFs): A New World of Targets and Treatments.

The importance of defining new molecules to fight cancer is of significant interest to the scientific community. In particular, it has been shown that cancer stem cells (CSCs) are a small subpopulation of cells within tumors with capabilities of self-renewal, differentiation, and tumorigenicity; on the other side, circulating tumor cells (CTCs) seem to split away from the primary tumor and appear in the circulatory system as singular units or clusters. It is becoming more and more important to discover new biomarkers related to these populations of cells in combination to define the network am

CAR-T cell therapy for the treatment of adult high-grade gliomas.

Treatment for malignant primary brain tumors, including glioblastoma, remains a significant challenge despite advances in therapy. CAR-T cell immunotherapy represents a promising alternative to conventional treatments. This review discusses the landscape of clinical trials for CAR-T cell therapy targeting brain tumors, highlighting key advancements like novel target antigens and combinatorial strategies designed to address tumor heterogeneity and immunosuppression, with the goal of improving outcomes for patients with these aggressive cancers.

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

Advancing Immunotherapy in Chronic Lymphocytic Leukemia.

The treatment of chronic lymphocytic leukemia (CLL) has significantly shifted from chemoimmunotherapy to targeted therapies like Bruton's tyrosine kinase and BCL2 inhibitors. Despite these advancements, CLL remains an incurable disease characterized by immune dysregulation, therapeutic resistance, and cumulative toxicities. To overcome these challenges, novel immunotherapeutic strategies are emerging as fundamentally different approaches that target immune-tumor interactions. These innovations include novel monoclonal antibodies, bispecific antibodies that redirect T cell cytotoxicity, chimeri

Targeted antineoplastic therapy in critically ill cancer patients: a multicenter analysis of the iCHOP registry.

Approximately 20% of intensive care unit (ICU) patients have cancer, and their prognosis has markedly improved in recent years. In addition to improved treatment in the ICU, this is a result of advancements in cancer therapies, including the use of targeted therapies (TTs), such as antibodies and small-molecule kinase inhibitors. Despite the increasing use of TT, there are currently no comprehensive studies examining critically ill cancer patients receiving TT in the ICU. We studied the clinical characteristics of a multicenter cohort of cancer patients who received TT in the ICU. To this end,

Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.

Cancer research has undergone a transformative change with the advent of high-throughput genomic technologies. Advances in next-generation sequencing accelerated the identification of somatic and germline alterations that drive tumorigenesis enabling the transition from traditional histology-based cancer classification to molecularly informed precision oncology. Large-scale sequencing initiatives and clinical genomic profiling facilitated the development of companion diagnostic assays and targeted therapies. Beyond targeted therapies, genomic innovations have also catalyzed the emergence of no

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

Mechanisms of resistance to tyrosine kinase inhibitor-targeted therapy and overcoming strategies.

Tyrosine kinase inhibitor (TKI)-targeted therapy has revolutionized cancer treatment by selectively blocking specific signaling pathways crucial for tumor growth, offering improved outcomes with fewer side effects compared with conventional chemotherapy. However, despite their initial effectiveness, resistance to TKIs remains a significant challenge in clinical practice. Understanding the mechanisms underlying TKI resistance is paramount for improving patient outcomes and developing more effective treatment strategies. In this review, we explored various mechanisms contributing to TKI resistan

Emerging Targets in Non-Small Cell Lung Cancer.

Lung cancer is responsible for a high burden of disease globally. Over the last two decades, the discovery of targetable oncogenic genomic alterations has revolutionized the treatment landscape for early-stage and advanced non-small cell lung cancer (NSCLC). New molecular drivers continue to emerge as promising therapeutic targets, including KRAS non-G12C, RAF/MEK, HER3, Nectin-4, folate receptor alpha, ITGB6, and PRMT5. In this review, we summarize the emerging molecular targets with a potential clinical impact in advanced NSCLC, elaborating on their clinical characteristics and specific mech

Chronic Lymphocytic Leukemia: 2025 Update on the Epidemiology, Pathogenesis, Diagnosis, and Therapy.

Disease overviewChronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.DiagnosisThe diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.Prognosis and stagingTwo clinical staging systems, Rai

Integration of circadian rhythms and immunotherapy for enhanced precision in brain cancer treatment.

Circadian rhythms significantly impact (patho)physiological processes, with disruptions linked to neurodegenerative diseases and heightened cancer vulnerability. While immunotherapy has shown promise in treating various cancers, its efficacy in brain malignancies remains limited. This review explores the nexus of circadian rhythms and immunotherapy in brain cancer treatment, emphasising precision through alignment with the body's internal clock. We evaluate circadian regulation of immune responses, including cell localisation and functional phenotype, and discuss how circadian dysregulation af

Rethinking corticosteroids use in oncology.

Corticosteroids (CSs), widely used in oncology for their anti-inflammatory and immunosuppressive properties, help manage cancer-related symptoms and side effects. However, their long-term use may negatively affect patient survival and exacerbate tumor progression. Elevated glucose and glutamine metabolism, disruption of vitamin D levels, and alterations in the microbiome are some of the key factors contributing to these adverse outcomes. Approaches such as ketogenic diets, fasting, sartans, and vitamin D supplementation have shown promise in providing similar benefits to CSs while mitigating t

NF-κB: master regulator of cellular responses in health and disease.

The NF-κB transcription control proteins play widespread roles in cellular behavior, regulating immune responses, inflammation, cell survival, proliferation, and development. Here, we attempt to comprehensively review these diverse functions and underlying mechanisms, leading readers to relevant references of both historic and topical importance. Because of the huge number of NF-κB control mechanisms and functions, and the vast literature that describes these, being comprehensive is a daunting task but we hope that readers will find clues to lead them to whatever understanding they may seek. A