# Therapy-Induced Senescence (TIS) and SASP: The p53-Mediated Interplay in Cancer Progression and Treatment

## TL;DR

This paper explores how cellular senescence, influenced by p53, can both fight and promote cancer, suggesting new treatment strategies.

## Contribution

The paper highlights the dual role of p53 in senescence and proposes strategic modulation of senescence as a new cancer treatment approach.

## Key findings

- p53 mutations can lead to senescence evasion and therapy resistance in cancer.
- Therapy-induced senescence can promote tumor progression through the SASP.
- Senolytics and immunotherapies are emerging as potential strategies to modulate senescence.

## Abstract

Cellular senescence, initially regarded as a potent tumor-suppressive mechanism, is now recognized as a double-edged sword that modulates the hallmarks of cancer. The tumor suppressor p53 typically orchestrates this process to inhibit tumorigenesis; however, mutations in p53 or its regulators can subvert this program, leading to senescence evasion and therapy resistance. In particular, therapy-induced senescence can paradoxically drive tumor progression via the senescence-associated secretory phenotype, which creates a pro-tumorigenic microenvironment dictated by p53-mediated regulation of NF-κB signaling. Here, we explore the p53-mediated senescence–cancer interplay and evaluate emerging therapies, including senolytics and immunotherapies. We propose that strategic modulation of senescence offers a promising paradigm for future anticancer therapy.