Highly conformal delivery of radiation therapy (RT) has revolutionized the treatment landscape for primary and metastatic liver cancers, yet concerns persist regarding radiation-induced liver disease (RILD). Despite advancements, RILD remains a major dose-limiting factor due to the potential damage to normal liver tissues by therapeutic radiation. The toxicity to normal liver tissues is associated with a multitude of physiological and pathological consequences. RILD unfolds as multifaceted processes, intricately linking various responses, such as DNA damage, oxidative stress, inflammation, cellular senescence, fibrosis, and immune reactions, through multiple signaling pathways. The DNA damage caused by ionizing radiation (IR) is a major contributor to the pathogenesis of RILD. Moreover, current treatment options for RILD are limited, with no established biomarker for early detection. RILD diagnosis often occurs at advanced stages, highlighting the critical need for early biomarkers to adjust treatment strategies and prevent liver failure. This review provides an outline of the diverse molecular and cellular mechanisms responsible for the development of RILD and points out all of the available biomarkers for early detection with the aim of helping clinicians decide on advance treatment strategies from a single literature recourse.

Background: Cellular senescence influences cancer progression through irreversible cell‐cycle arrest, immune surveillance, and paracrine signaling mediated by the senescence‐associated secretory phenotype (SASP). SASP comprises inflammatory cytokines, chemokines, growth factors, and matrix‐remodeling enzymes that regulate the tumor microenvironment (TME). Objective: This review describes the current evidence on the mechanisms of SASP induction, its condition‐dependent roles in cancer, TME remodeling, and emerging strategies targeting senescent cells and SASP signaling. Methods: Relevant literature was identified through searches on PubMed, Scopus, Web of Science, and Google Scholar using keywords related to cellular senescence, SASP, cancer, TME, senolytics, and senomorphics. Peer‐reviewed English‐language studies published primarily between January 2000‐ March 2026 were considered, including preclinical (in vitro, in vivo), and clinical studies investigating SASP induction and regulation, its role in cancer progression and TME remodeling, and therapeutic strategies targeting senescent cells or SASP signaling. Interpretation of the Retrieved Articles: SASP exhibits both tumor‐suppressive and tumor‐promoting activities depending on cellular and tissue condition. While transient SASP may enhance antitumor immunity and suppress early tumorigenesis, persistent SASP, particularly during therapy‐induced senescence (TIS), can promote tumor growth, angiogenesis, immune evasion, cancer stemness, metastasis, and therapeutic resistance. Senolytics and senomorphics have therefore emerged as promising approaches for targeting senescent cells and their detrimental secretory effects. SASP‐associated molecules also show potential as biomarkers, although specificity and tissue‐dependent heterogeneity remain major challenges. Conclusion: Current evidence supports SASP as a major regulator of the TME and an important determinant of cancer progression and therapeutic response. Understanding the condition‐dependent functions of SASP is critical for developing effective senescence‐targeted cancer therapies.