Cellular senescence: Silent operator and therapeutic target in cancer

Abstract

The process of carcinogenesis and its progression involves an intricate interplay between a number of signaling networks, metabolic pathways and the microenvironment. These include an alteration in the cellular redox metabolism and deregulation of cell cycle checkpoints. Similar to the dichotomy of redox signaling in cancer cell fate and state determination, a diverging effect of an irreversible cell cycle arrest or senescence on carcinogenesis has been demonstrated. In this regard, while overwhelming oxidative stress has a damaging effect on tissue architecture and organ function and promotes death execution, a mild “pro‐oxidant” environment is conducive for cell proliferation, growth and survival. Similarly, cellular senescence has been shown to elicit both a tumor suppressor and an oncogenic effect in a context‐dependent manner. Notably, there appears to be a crosstalk between these two critical regulators of cell fate and state, particularly from the standpoint of the divergent effects on processes that promote or abate carcinogenesis. This review aims to provide an overview of these overarching themes and attempts to highlight critical intersection nodes, which are emerging as potential diagnostic and/or therapeutic targets for novel anticancer strategies.

ARID1A knockdown enhances carcinogenesis features and aggressiveness of Caco-2 colon cancer cells: An in vitro cellular mechanism study

“…Cellular senescence is a cell protective mechanism that can be detected by measuring the SA-β-gal activity 52 , 53 . Several lines of evidence have reported that suppression of cellular senescence is associated with the enhanced carcinogenesis 54 , 55 . Interestingly, several cancer cells can undergo senescence after exposure to chemotherapeutic agents 56 - 58 .…”

Cellular Senescence-Related Genes: Predicting Prognosis in Gastric Cancer

“…Cellular senescence can play an essential role in immune surveillance to ensure that senescent cancer cells are eliminated ( Prasanna et al, 2021 ). Nowadays, cellular senescence is emerging as a potentially novel anticancer strategy ( Ramu et al, 2021 ). It could help guide effective anticancer therapy strategies by exploring the cellular senescence patterns of GC.…”

Integrated analysis of single‐cell sequencing and weighted co‐expression network identifies a novel signature based on cellular senescence‐related genes to predict prognosis in glioblastoma

“…37 In recent years, cellular senescence is gaining recognition as a promising and innovative approach in the field of anticancer strategies. 38 The nomogram had good performance in predicting survival outcomes of GBM patients. The top 30 potential anti-cancer small molecular compounds with higher drug sensitivity scores for high-or low-risk groups were identified, which might be effective to treat GBM patients.…”

“…Cellular senescence is essential in immune surveillance, ensuring the elimination of senescent cancer cells 37 . In recent years, cellular senescence is gaining recognition as a promising and innovative approach in the field of anticancer strategies 38 . It has the potential to guide the development of effective anticancer therapies by examining the cellular senescence patterns in GBM.…”