95% of researchers rate our articles as excellent or good
Learn more about the work of our research integrity team to safeguard the quality of each article we publish.
Find out more
REVIEW article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1509173
Current Status of KRAS G12C inhibitors in NSCLC and the Potential for Combination with Anti-PD-(L)1 Therapy: A Systematic Review
Provisionally accepted- Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
In recent years, precision medicine for non-small cell lung cancer (NSCLC) has made significant strides, particularly with advancements in diagnostic and therapeutic technologies. Targeted therapies and Anti-PD-(L)1 Therapies have emerged as vital treatment options, yet KRAS mutations, especially KRAS G12C, have been historically difficult to address. Due to the unique activation mechanism of KRAS G12C has led to the development of specific inhibitors, such as AMG 510 and MRTX849, which show promising therapeutic potential. However, results from the CodeBreaK 200 Phase III trial indicated that AMG 510 did not significantly improve overall survival compared to docetaxel. Resistance after prolonged use of KRAS G12C inhibitors continues to pose a challenge, prompting interest in new drugs and combination strategies. KRAS mutations can impair tumorinfiltrating T cell function and create an immunosuppressive tumor microenvironment, making the combination of KRAS G12C inhibitors with anti-PD-(L)1 therapies particularly appealing. Preliminary data suggest these combinations may enhance both survival and quality of life, though safety concerns remain a barrier. Ongoing research is crucial to refine treatment regimens and identify suitable patient populations. This review focuses on the development of KRAS G12C inhibitors in monotherapy and combination therapies for NSCLC, discussing major clinical trials and future research directions.
Keywords: Non-small cell lung cancer (NSCLC), targeted therapies, KRAS G12C inhibitors, Anti-PD-(L)1 Therapies, combination therapy
Received: 10 Oct 2024; Accepted: 26 Mar 2025.
Copyright: © 2025 Zhang, Wang, Wu, Zhang and Ji. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Mei Ji, Department of Oncology, The Third Affiliated Hospital of Soochow University, Changzhou, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.