Molecular Signatures of Cellular Senescence in Cancer: A Critical Review of Prognostic Implications and Therapeutic Opportunities

Mechanisms of Ageing and Development, Journal Year: 2025, Volume and Issue: unknown, P. 112052 - 112052

Published: March 1, 2025

Language: Английский

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Targeting the Senescent Tumor Microenvironment to Sensitize Immunotherapy

Highlights in Science Engineering and Technology, Journal Year: 2025, Volume and Issue: 139, P. 260 - 271

Published: April 28, 2025

The tumor microenvironment (TME) plays a pivotal role in cancer progression, metastasis, and therapeutic resistance. Cellular senescence within the TME, characterized by irreversible growth arrest senescence-associated secretory phenotype (SASP), profoundly impacts biology immunotherapy efficacy. senescent TME promotes growth, invasion, metastasis through complex interactions between cells, SASP factors, extracellular matrix (ECM). Simultaneously, senescence-induced alterations immune cell function, including T exhaustion, macrophage polarization, impaired natural killer (NK) cytotoxicity, contribute to an immunosuppressive niche that hinders immunosurveillance fosters evasion. Mounting evidence suggests is critical mediator of resistance checkpoint inhibitors (ICIs). Senescence-associated changes dampen antitumor immunity reducing CD8+ infiltration functionality while promoting accumulation populations such as regulatory cells (Tregs) myeloid-derived suppressor (MDSCs). Consequently, strategies targeting have emerged promising approaches enhance ICI Senolytic agents, inhibitors, combinatorial therapies aimed at eliminating modulating SASP, reprogramming shown potential preclinical models sensitize tumors immunotherapy. As our understanding evolves, it becoming increasingly clear multifaceted approach integrating TME-targeted interventions with necessary overcome improve patient outcomes. Future research should focus on elucidating molecular mechanisms underlying senescence-driven resistance, identifying robust biomarkers predict treatment response, developing novel synergize ICIs. By harnessing approaches, we can expand scope efficacy immunotherapy, ultimately leading improved survival quality life for patients.

Language: Английский

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ProgModule: A novel computational framework to identify mutation driver modules for predicting cancer prognosis and immunotherapy response

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: May 8, 2025

Cancer originates from dysregulated cell proliferation driven by driver gene mutations. Despite numerous algorithms developed to identify genomic mutational signatures, they often suffer high computational complexity and limited clinical applicability. Here, we presented ProgModule, an advanced framework designed mutation modules for cancer prognosis immunotherapy response prediction. In introduced the Prognosis-Related Mutually Exclusive Mutation (PRMEM) score, which optimizes balance between exclusive coverage incorporation of combination mechanisms critical prognosis. Applying BLCA HNSC cohorts, ProgModule successfully identified that stratify patients into distinct prognostic subgroups, these could serve as effective biomarker. Extending our method diverse cancers, robust performance stability across model parameters, including stopping criteria network topology. Moreover, analysis suggested can predict immunotherapeutic benefit more effectively than existing signatures. Further analyses based on published CRISPR data indicated genes within may potential therapeutic targets. Altogether, emerges a powerful tool identifying biomarkers, be used targets cancer, offering new insights precision oncology.

Language: Английский

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T-Cell Senescence: Unlocking the Tumor Immune “Dark Box” - A Multidimensional Analysis from Mechanism to Tumor Immunotherapeutic Intervention

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: unknown

Published: May 1, 2025

Language: Английский

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