2. Academic Validation
  3. The potential therapeutic regimen for overcoming resistance to osimertinib due to rare mutations in NSCLC

The potential therapeutic regimen for overcoming resistance to osimertinib due to rare mutations in NSCLC

  • iScience. 2023 Jun 12;26(7):107105. doi: 10.1016/j.isci.2023.107105.
Rui Han 1,  Caiyu Lin 1,  Chong Zhang 2,  Jun Kang 1,  Conghua Lu 1,  Yiming Zhang 1,  Yubo Wang 1,  Chen Hu 1,  Yong He 1
Affiliations

Affiliations

  • 1 Department of Respiratory Disease, Daping Hospital, Army Medical University, Chongqing, China.
  • 2 Department of Ultrasound, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
PMID: 37416479 DOI: 10.1016/j.isci.2023.107105
Abstract

The mechanisms of osimertinib resistance have not been well characterized. We conducted next-generation Sequencing to recognize novel resistance mechanism and used cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models to evaluate the anti-proliferative effects of aspirin in vivo and in vitro. We observed that PIK3CG mutations led to acquired resistance to osimertinib in a patient and further confirmed that both PIK3CG and PIK3CA mutations caused osimertinib resistance. Mechanistically, the expression of PI3Kγ or PI3Kα was up-regulated after PIK3CG or PIK3CA lentivirus transfection, respectively, and which can be effectively suppressed by aspirin. Lastly, our results from in vivo studies indicate that aspirin can reverse osimertinib resistance caused by PIK3CG or PIK3CA mutations in both CDX and PDX models. Herein, we first confirmed that mutations in PIK3CG can lead to resistance to osimertinib, and the combined therapy may be a strategy to reverse PIK3CG/PIK3CA mutation-induced osimertinib resistance.

Keywords

Cancer; Molecular genetics; Molecular interaction.

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