KRAS G12C mutation: from undruggable target to potentially agnostic biomarker

• Type of Material: Article
• Authors: Badi El Osta, Emory University
• Language: English
• Date: 2023-05-23
• Publisher: AME PUBLISHING COMPANY
• Publication Version: Final Published Version
• Copyright Statement: © 2009 - 2024 AME Publishing Company
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.21037/tlcr-23-174
• Title of Journal or Parent Work: TRANSLATIONAL LUNG CANCER RESEARCH
• Volume: 12
• Issue: 6
• Start Page: 1147
• End Page: 1151
• Grant/Funding Information: None
• Keywords: Kristen rat sarcoma (KRAS); Oncology; Respiratory System; targeted therapy; Science & Technology; precision oncology; OSIMERTINIB; CHEMOTHERAPY; CELL LUNG-CANCER; Life Sciences & Biomedicine; Non-small cell lung cancers (NSCLC)
• Research Categories: Health Sciences, Oncology; Health Sciences, Pharmacology

Abstract

Targeted therapies for KRAS-mutant non-small cell lung cancer: from preclinical studies to clinical development-a narrative review”, I comment on the next steps in KRAS inhibitors clinical trial development after a concise review of this topic. KRAS activating somatic mutations represent the most common genetic alteration in non-small cell lung cancers (NSCLC) (2,3). They are reported in 25% to 30% of non-small cell lung adenocarcinomas and in approximately 4% of squamous cell lung carcinomas. KRAS mutations commonly occur in hotspots at codon 12 (the most common, KRAS G12C) and codon 13 (3). They were identified and remained hard to treat for more than four decades. They recently joined the ranks of targetable molecular drivers in NSCLC with the Food and Drug Administration (FDA) approval of two KRAS G12C selective covalent inhibitors, sotorasib and adagrasib (4,5).