PIKing up and AKTing on Resistance Mutations in Osimertinib-Treated EGFR-Mutated NSCLC-Reference-Cited by-同舟云学术

PIKing up and AKTing on Resistance Mutations in Osimertinib-Treated EGFR-Mutated NSCLC

Published:2024-07-17 Issue:18 Volume:30 Page:3968-3970
ISSN:1078-0432
Container-title:Clinical Cancer Research
language:en
Short-container-title:

Author:

Vokes Natalie I.¹²^ORCID,Le Xiuning¹^ORCID,Yap Timothy A.¹³⁴⁵^ORCID

Affiliation:

1. Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas. 1

2. Department of Genomic Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas. 2

3. Department of Investigational Cancer Therapeutics (Phase I Clinical Trials Program), The University of Texas MD Anderson Cancer Center, Houston, Texas. 3

4. Therapeutics Discovery Division, The University of Texas MD Anderson Cancer Center, Houston, Texas. 4

5. Khalifa Institute for Personalized Cancer Therapy, The University of Texas MD Anderson Cancer Center, Houston, Texas. 5

Abstract

Summary A recent study identified high rates of PI3K–AKT pathway mutations from the FLAURA and AURA3 osimertinib trials and pre-clinically validated that these mutations decreased osimertinib sensitivity in EGFR-mutated non–small cell lung cancer. The AKT inhibitor capivasertib was found to overcome this resistance, providing an important rationale for the development of AKT inhibitors in non–small cell lung cancer. See related article by Grazini et al., p. 4143

Publisher

American Association for Cancer Research (AACR)

Link

https://aacrjournals.org/clincancerres/article-pdf/doi/10.1158/1078-0432.CCR-24-1188/3475346/ccr-24-1188.pdf

Reference18 articles.

1. Overcoming osimertinib resistance with AKT inhibition in EGFRm-driven non-small-cell-lung-cancer with PIK3CA/PTEN alterations;Grazini;Clin Cancer Res,2024

2. Convergent Akt activation drives acquired EGFR inhibitor resistance in lung cancer;Jacobsen;Nat Commun,2017

3. PIK3CA mutations in non-small cell lung cancer (NSCLC): genetic heterogeneity, prognostic impact and incidence of prior malignancies;Scheffler;Oncotarget,2015

4. Lack of PTEN expression in non-small cell lung cancer could be related to promoter methylation;Soria;Clin Cancer Res,2002

5. PTEN expression in non-small-cell lung cancer: evaluating its relation to tumor characteristics, allelic loss, and epigenetic alteration;Marsit;Hum Pathol,2005