This commentary examines the ambivalent role of cellular senescence in the earliest stages of cancer, noting that it initially serves as a vital but transient tumor-suppressive barrier that eventually transitions into a pro-tumorigenic state. The authors analyze how this process extends beyond epithelial cells, highlighting the deleterious impact of senescence in stromal and immune cells that collectively reshape the precancer tissue microenvironment (PreTME). The text reviews promising precision interception strategies, including pharmacological agents (senolytics and senomorphics) and modifiable lifestyle interventions such as exercise and dietary restrictions. Furthermore, the source outlines critical hurdles for the field, primarily focusing on the necessity of developing reliable senescence markers and computational tools to effectively map and target these cells for prevention.

References:

• Hoi X P, Stangis M M, Glass S E, et al. Cellular senescence in precancer lesions and early-stage cancers[J]. Cancer cell, 2025.