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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• Rat Sarcoma (RAS) driven cancers are a significant focus in cancer research.
• Targeting RAS-mutated cancers remains a challenge despite decades of study.
• Recent research highlights RAS's role beyond cancer cell proliferation.

Purpose of the Study:

• To systematically review the mechanisms of RAS oncogene-mediated alterations in DNA replication and DNA damage response (DDR) pathways.
• To explore the connection between RAS mutations and cytosolic DNA accumulation, innate immune activation, and senescence in cancer.
• To speculate on potential therapeutic strategies for RAS-mutated lung cancers.

Main Methods:

• Systematic review of existing literature on RAS oncogene function.
• Analysis of molecular mechanisms linking RAS to DNA replication and DDR.
• Exploration of downstream effects including DNA accumulation and immune response.

Main Results:

• RAS oncogenes significantly alter DNA replication and DNA damage response (DDR) pathways.
• RAS-driven cancers exhibit cytosolic DNA accumulation, activating innate immunity and senescence.
• These molecular alterations create vulnerabilities in RAS-addicted cancers.

Conclusions:

• Targeting DNA replication, DNA repair, and the cGAS-STING pathway are potential strategies for RAS-mutated lung cancers.
• Combination therapies targeting these pathways may enhance treatment efficacy.
• Overcoming challenges associated with RAS mutations may be possible through novel therapeutic approaches.