Molecular signatures of cellular senescence in cancer: a critical review of prognostic implications and therapeutic opportunities

Abstract

Cellular senescence is a state of permanent loss of proliferative capacity. Therefore, cells that reach a senescent state prevent tumor initiation, acting as an anti-tumor mechanism. However, despite not being proliferative, senescent cells have high secretory activity, constituting the Senescence-Associated Secretory Phenotype (SASP). SASP includes thousands of soluble molecules and extracellular vesicles, through which senescent cells can affect other cells and the extracellular matrix. In advanced tumors, the enrichment of senescent cells can have anti- or pro-tumor effects depending on features like SASP composition, tumor microenvironment (TME) composition, the anatomic site, histopathologic characteristics of malignancy, and tumor molecular background. We reviewed the studies assessing the impact of the senescence status, measured by mRNA or lncRNA molecular signatures, in the prognosis and other clinically relevant information in cancer, including anti-tumor immunity and response to therapy. We discussed the pros and cons of different strategies to define those molecular signatures and the main limitations of the studies. Finally, we also raised clinical challenges regarding the crossroad between cellular senescence and cancer prognosis, including some therapeutic opportunities in the field.