Oncogenic RAS in Cancers from the DNA Replication Stress and Senescence Perspective

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2024 Dec 17

PMID 39682179

Authors

Herve Techer

Samira Kemiha

Xieraili Aobuli

Arun Mouli Kolinjivadi

Affiliations

Soon will be listed here.

Abstract

Rat Sarcoma (RAS)-driven cancers have been one of the main foci in the field of cancer science for over four decades. Despite significant improvement in understanding the biology of RAS oncogene, the method to target RAS-mutated cancers is still unclear. In recent years, the role for RAS beyond its hyperproliferation has been extensively documented. In this review, we systematically address and dwell on the details of the mechanisms of RAS oncogene-mediated alteration in the DNA replication and DNA damage response (DDR) pathways, focusing on lung cancers. We further extend this molecular connection towards cytosolic DNA accumulation, innate immune activation and senescence in RAS-addicted cancers. At the end, we briefly speculate on the potential strategies for targeting RAS mutated lung cancers, considering various approaches targeting DNA replication, DNA repair and the cGAS-STING pro-inflammatory pathway. These new lines of therapy, especially when used in combinations, may enhance treatment efficacy and overcome the challenges associated with these mutations.

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