Get started
Work

First-line treatment strategies and potential prognostic factors in patients with KRAS G12C-mutant non-small cell lung cancer

Year: 2025
Type: article
Abstract: : The treatment landscape for KRASG12C-mutant non-small cell lung cancer (NSCLC) has rapidly evolved over the past few years. Once considered an undruggable mutation, KRASG12C now has standard, US Food and Drug Administration (FDA)-approved targeted therapies as well as multiple novel therapies under investigation. This breakthrough began with sotorasib, the first-in-class US FDA-approved inhibitor, and has expanded to include multiple oral KRASG12C inhibitors being studied either as monotherapy or in combination with other agents. Despite these advances, key challenges and many uncharted areas remain. These include defining optimal treatment sequencing, identifying the best-in-class inhibitor in terms of therapeutic index, and improving efficacy through combination strategies. Potential combination approaches involve pairing KRASG12C with immune checkpoint inhibitors, platinum-based chemotherapy, or other inhibitors of cell proliferation or survival pathways. Additionally, understanding mechanisms of resistance to KRASG12C inhibitors remains a critical research priority. Addressing these challenges is critical to advancing personalized medicine in KRASG12C-mutant NSCLC and incorporating KRASG12C targeted therapy into the first-line setting, where therapy selection is tailored to the tumor biology. This review outlines the therapeutic and prognostic significance of KRASG12C mutation in NSCLC, with emphasis on clinical outcomes with immune checkpoint inhibition, current standard-of-care treatments, and emerging targeted therapies under investigations.
DOI: 10.21037/actr-25-63
Authors: Malak Alharbi, Nour Nassour, Vaishali Deenadayalan, Grace K. Dy
Language: English
Field: Medicine
Open Access status: hybrid
OpenAlex ID: W7083694399
FWCI:
Cites:
Cited by:
Related to: