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KRAS G12C Mutations in NSCLC: From Target to Resistance
Alfredo Addeo1, Giuseppe Luigi Banna2, Alex Friedlaender1,3
1Swiss Cancer Center Leman, Oncology Department, Switzerland University of Geneva, University Hospital Geneva, 1205 Geneva, Switzerland.
This review explores Kirsten Rat Sarcoma (KRAS) mutations in non-small cell lung cancer (NSCLC). It details KRAS biology, focusing on resistance mechanisms and their clinical impact for advanced NSCLC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Lung cancer is a leading cause of cancer death globally.
- Treatments for advanced non-small cell lung cancer (NSCLC) have improved with immune checkpoint inhibitors and targeted therapies.
- Resistance mechanisms limit the long-term efficacy of these treatments.
Purpose of the Study:
- To review the biology of Kirsten Rat Sarcoma (KRAS) oncogene in NSCLC.
- To focus on primary and secondary resistance mechanisms associated with KRAS mutations.
- To discuss the clinical implications of these resistance mechanisms.
Main Methods:
- Literature review of KRAS mutations in NSCLC.
- Analysis of biological mechanisms of resistance.
- Discussion of clinical relevance and therapeutic strategies.
Main Results:
- KRAS mutations are the most common oncogenic driver in NSCLC (20-25% of cases), predominantly in adenocarcinoma and smokers.
- Emerging drugs show promising activity against KRAS-mutated NSCLC.
- Understanding resistance mechanisms is crucial for improving patient outcomes.
Conclusions:
- KRAS mutations represent a significant challenge in NSCLC treatment due to evolving resistance.
- Further research into KRAS biology and resistance pathways is essential for developing more effective therapies.
- Targeting KRAS and overcoming resistance mechanisms hold promise for managing advanced NSCLC.
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