Aug 2026· Cancers· Vol 18, pp. 2593· 0 citations· 259 references
Medicine
TL;DR
This review explains how cancer cells bypass standard therapies and highlights next-generation immune targets currently being developed to overcome resistance, and examines how combining new immune-boosting drugs with traditional treatments like chemotherapy, radiation, and novel targeted therapies can weaken cancer defenses.
Abstract
Simple Summary Gastrointestinal cancers remain among the most challenging diseases to treat because many tumors contain complex immune system suppression mechanisms that stop the body from destroying cancer cells. While current immunotherapy drugs have transformed care for a small group of patients, most gastrointestinal tumors quickly resist these treatments. This review explains how cancer cells bypass standard therapies and highlights next-generation immune targets currently being developed to overcome this resistance. We examine how combining new immune-boosting drugs with traditional treatments like chemotherapy, radiation, and novel targeted therapies can weaken cancer defenses. Finally, we explore advanced blood tests and digital tissue profiling methods designed to help doctors predict which patients will benefit most from these therapies. By connecting basic tumor biology with innovative clinical strategies, this review aims to help researchers design smarter, more focused and effective treatment combinations for patients with gastrointestinal cancers.
This review summarizes emerging therapeutic strategies for EOC, their mechanisms of action, and their potential to overcome treatment resistance, and covers molecularly targeted therapies, immunotherapies, metabolic and epigenetic approaches, cellular and gene therapies, targeted drug-delivery systems, and locoregional and physical modalities.
Zofia Pietrasik, Mikołaj Kapała, Joanna Pietrasik et al.· Cancers· 0 citations
Simple Summary Gastrointestinal cancers are among the most common and deadly cancers worldwide. Their treatment is becoming increasingly complex because many new therapies no longer depend only on the organ in which the tumor develops, but also on specific biological features of the cancer cells. This review explains how modern biological and targeted therapies work in gastrointestinal cancers, which biomarkers help identify patients who may benefit from them, and how these treatments can be combined with surgery, chemotherapy, radiotherapy, or immunotherapy. The aim is to provide a clear overview of current and emerging treatment strategies, including immune checkpoint inhibitors, anti-HER2 therapies, antiangiogenic drugs, anti-EGFR antibodies, and newer approaches targeting CLDN18.2 and FGFR2b. By summarizing mechanisms, biomarkers, and clinical use, this review may help researchers and clinicians better understand the changing landscape of personalized treatment for gastrointestinal cancers.
Marek Kos, K. Bojarski, Milena Czosnek et al.· Cancers· 0 citations
Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of solid tumors, yet only a limited subset of patients achieves durable disease control. While China has emerged as a major contributor to global ICI development, a comprehensive synthesis of recent trial data and resistance mechanisms is urgently needed to guide clinical practice. This review examines the evolving landscape of ICI‐based combination therapies, including regimens that combine ICI with chemotherapy, targeted therapy, antibody–drug conjugates, antiangiogenic agents, and radiotherapy, which have expanded first‐line treatment options across multiple solid tumors and, in selected settings, have improved disease control or survival beyond historical monotherapy benchmarks. An in‐depth analysis of the molecular mechanisms underlying primary and acquired resistance to ICIs is then provided, drawing on recent advances in multiomics. Building on this framework, emerging, mechanism‐matched strategies designed to overcome specific resistance nodes are critically evaluated. Finally, the promise of integrating spatial transcriptomics and artificial intelligence to help shift ICI therapy from empirical combination toward mechanism‐guided precision immuno‐oncology is discussed. By bridging the gap between clinical evidence and molecular insights, this review offers a perspective that may help accelerate the rational design of next‐generation ICI‐based strategies and improve patient outcomes.
This review presents a systematic synthesis of the principal tumor immunotherapy strategies and their corresponding resistance mechanisms, finding that combination therapies and personalized treatment strategies grounded in TME profiling and biomarkers represent critical future directions.
Immune checkpoint inhibitors (ICIs), particularly antibodies targeting PD-1/PD-L1 and CTLA-4, have reshaped the treatment landscape of lung cancers, most notably non-small cell lung cancer (NSCLC). Nevertheless, only a subset of patients achieve durable benefit due to primary and acquired resistance that arises from tumor-intrinsic factors (e.g., oncogenic drivers and adaptive signaling), tumor-extrinsic determinants in the tumor microenvironment (TME) (e.g., impaired T-cell infiltration and immunosuppressive myeloid populations), and the dynamic evolution of biomarkers. Accordingly, current clinical and translational efforts in lung cancer focus on rational combination strategies—ICIs with chemotherapy, radiotherapy, and targeted agents (including RTK- and KRAS-pathway inhibitors)—as well as alternative approaches that modulate antigen presentation, myeloid regulation, and cancer stemness. In this review, we define a lung cancer–centered scope and summarize (i) established and emerging ICI-based regimens in lung cancer, (ii) mechanisms of resistance relevant to NSCLC and SCLC, (iii) biomarker integration for patient selection and monitoring, and (iv) future directions to optimize efficacy and safety through combinatory and alternative immunotherapeutic strategies.
Junyoung Park, Choong‐Hwan Kwak, Yu-Chan Chang et al.· Frontiers in Immunology· 0 citations
: Tumor immunotherapy has fundamentally transformed modern oncology. This approach essentially mobilizes the patient’s own immune defenses to identify and eliminate cancer cells— a strategy that continues to redefine how we treat cancer today.This review traces the history of cancer immunotherapy and explains how the immune system detects and controls tumors — including the ideas of immune surveillance and immunoediting. It also outlines key ways tumors evade immunity. These include PD-1/PD-L1 signal transduction, suppression by regulatory T cells, and how the tumor microenvironment has an immunosuppressive character. Looking ahead, the review emphasizes future directions and explores opportunities for combination treatments. It also discusses the potential of personalized therapies and the development of new strategies. Challenges such as drug resistance, treatment-related side effects, and limited effectiveness in solid tumors are analyzed, with proposed solutions. Research shows that through deeper mechanistic understanding, diverse treatment options, and continuous innovation, tumor immunotherapy brings new hope for long-term disease control and possibly even curing cancer.
Y. Zhang· Proceedings of the 1st Inter...· 0 citations
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