Skip to main content

PERSPECTIVE article

Front. Oncol.
Sec. Thoracic Oncology
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1459737
This article is part of the Research Topic The Molecular Mechanisms and Therapeutic Implications of Protein Kinase Inhibitors in Cancer Therapy View all 4 articles

Clinical perspectives on the value of testing for STK11 and KEAP1 mutations in advanced NSCLC

Provisionally accepted
Michelle Shiller Michelle Shiller 1*Melissa Johnson Melissa Johnson 2Robert Auber Robert Auber 3Sandip Pravin Patel Sandip Pravin Patel 4
  • 1 Baylor University Medical Center, Dallas, United States
  • 2 Sarah Cannon Research Institute, Nashville, Tennessee, United States
  • 3 Other, Nashville, TN, United States
  • 4 Moores Cancer Center, School of Medicine, University of California, San Diego, La Jolla, California, United States

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

    Standard first-line therapy for patients with metastatic non-small cell lung cancer (mNSCLC) without identified actionable mutations consists of regimens comprising immune checkpoint inhibitors (ICIs), alone or in combination with platinum-based chemotherapy (CTx). However, approximately 20-30% of patients with mNSCLC (including some patients with high tumor programmed cell death ligand-1 expression) display primary resistance to ICIs, either alone or in combination with CTx. Mutations in tumor suppressor genes serine/threonine kinase 11 (STK11), and Kelch-like ECH-associated protein 1 (KEAP1) often detected in patients with Kirsten rat sarcoma virus mutations, are associated with an aggressive disease phenotype and resistance to standard ICI regimens. Consequently, there is an important need for effective treatments for patients with NSCLC with STK11 or KEAP1 mutations.In this article, we describe new data on the prevalence of STK11 and KEAP1 mutations in a large clinical population, consider practicalities around the detection of these mutations using available biomarker testing methodologies, and describe experiences of managing some of these difficult-totreat patients in our clinical practice.

    Keywords: protein serine-threonine kinases1, kelch-like ECH-associated protein 12, c proto-oncogene proteins p21(ras)3, Carcinoma, non-small-cell Lung4, immunotherapy5

    Received: 04 Jul 2024; Accepted: 05 Nov 2024.

    Copyright: © 2024 Shiller, Johnson, Auber and Patel. 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: Michelle Shiller, Baylor University Medical Center, Dallas, United States

    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.