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REVIEW article

Front. Oncol.
Sec. Thoracic Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1357898
This article is part of the Research Topic KRAS in Stage IV Non-Small Cell Lung Cancer View all 6 articles

Resistance to KRAS inhibition in stage IV lung cancer

Provisionally accepted
Katherina B. Sreter Katherina B. Sreter 1Maria J. Catarata Maria J. Catarata 2Maximilian von Laffert Maximilian von Laffert 3Armin Frille Armin Frille 4*
  • 1 University Hospital Centre Zagreb, Zagreb, Croatia
  • 2 Braga Hospital, Braga, Braga, Portugal
  • 3 Institute of Pathology, University Hospital Leipzig, Leipzig, Lower Saxony, Germany
  • 4 University Hospital Leipzig, Leipzig, Germany

The final, formatted version of the article will be published soon.

    Lung cancer remains the leading cause of cancer death globally. More than 50% of new cases are diagnosed in an advanced or metastatic stage, thus contributing to the poor survival of such patients. Mutations in the KRAS (Kirsten rat sarcoma virus) gene occur in nearly a third of lung adenocarcinoma and have for decades been deemed an 'undruggable' target. Yet, in recent years, a growing number of small molecules, such as the GTPase inhibitors, has been investigated in clinical trials of lung cancer patients harboring KRAS mutations, yielding promising results with improved outcomes. Currently, there are only two approved targeted therapies (adagrasib and sotorasib) for advanced or metastatic KRAS-mutated NSCLC from the second-line setting onwards. In this narrative review, we will focus on KRAS, its molecular basis, the role of its co-mutations, clinical evidence for its inhibition, putative mutation to resistance, and future strategies to overcome resistance to KRAS inhibition.

    Keywords: Non-small cell lung cancer, Lung Adenocarcinoma, KRAS, co-mutations, resistance to therapy. Word count:11, 983

    Received: 18 Dec 2023; Accepted: 06 May 2024.

    Copyright: © 2024 Sreter, Catarata, von Laffert and Frille. 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: Armin Frille, University Hospital Leipzig, Leipzig, Germany

    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.