Unraveling senescence in cancer: mechanistic complexities and therapeutic opportunities.

Abstract

Senescence is a pivotal cellular process, which also plays a major role in development, immune regulation, tissue repair, and aging, triggered by stressors such as telomere shortening, oncogene activation, and DNA damage. Characterized by distinct morphological and molecular features, senescence is known to act as a tumor suppressive mechanism through irreversible cell cycle arrest. However, emerging studies reveal a paradox: prolonged senescence in cancer cells can drive tumorigenesis via the senescence-associated secretory phenotype, promoting proliferation, invasion, and metastasis. This comprehensive review elucidates the molecular intricacies of senescence to induce growth arrest, enhance immune surveillance, and favorably modulate the tumor microenvironment to inhibit cancer progression. Additionally, it examines the senescence-inducing effects of conventional therapies and explores the potential of emerging therapies, including targeted therapies and chimeric antigen receptor T cell therapy. The present review also highlights the promise of senotherapeutic strategies in selectively targeting senescent cells to improve therapeutic outcomes. It discusses the innovative integration of machine learning tools for biomarker discovery and patient stratification offering a transformative approach to improve cancer treatment efficacy.