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CASE REPORT article

Front. Oncol.

Sec. Thoracic Oncology

Acquired EGFR L858R mutation following ALK-TKI resistance in lung adenocarcinoma: a Case Report

Provisionally accepted
Chunxiang LUOChunxiang LUO1,2,3*Wenying PengWenying Peng1,2,3Ruying DuanRuying Duan1,2,3Runxiang YangRunxiang Yang1,2,3Susu QuSusu Qu1,2,3Mengyuan DongMengyuan Dong1,2,3,4Ruofan ChenRuofan Chen1,2,3
  • 1Yunnan Cancer Hospital, Kunming, China
  • 2The Third Affiliated Hospital of Kunming Medical University, Kunming, China
  • 3Peking University Cancer Hospital Yunnan, Kunming, China
  • 4Kunming Xishan District People's Hospital, Kunming, China

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Reports of secondary mutations in mutual exclusive driver genes after resistance to targeted therapy are rare. We present a patient with Anaplastic lymphoma kinase (ALK) fusion lung adenocarcinoma who received sequential treatment with ALK tyrosine kinase inhibitor (TKI) (crizotinib, PFS:32.3 months and then conteltinib, PFS: 29 months). Upon further disease progression, a lung biopsy and next-generation sequencing (NGS) revealed acquired secondary driver mutations including Epidermal Growth Factor Receptor (EGFR) L858R and ALK mutation of F1174L. Subsequently, the patient switched to third generation EGFR-TKI treatment with almonertinib. This case suggests EGFR mutation is one of the mechanisms of ALK-TKI resistance , highlights the value of re-biopsy in identifying potentially targetable resistance mechanisms and underscores the spatiotemporal heterogeneity of tumors under the selective pressure of ALK-TKI.

Keywords: Anaplastic lymphomakinase, case report, epidermal growth factor receptor, Lung Adenocarcinoma, targeted therapy

Received: 03 Jan 2026; Accepted: 12 Feb 2026.

Copyright: © 2026 LUO, Peng, Duan, Yang, Qu, Dong and Chen. 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: Chunxiang LUO

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.

Supplementary Material