AUTHOR=Zeng Zhu , Wang Tao , He Junjun , Wang Yuehong 

TITLE=ALK-R3HDM1 and EML4-ALK fusion as a mechanism of acquired resistance to gefitinib: A case report and literature review

JOURNAL=Frontiers in Oncology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1010084

DOI=10.3389/fonc.2022.1010084

ISSN=2234-943X

ABSTRACT=<p>We report a case with a novel <italic>ALK-R3HDM1</italic> and <italic>EML4-ALK</italic> dual fusion that might be a delicate mechanism for the acquired resistance of epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor (TKI). A patient with <italic>EGFR</italic> L858R lung adenocarcinoma developed disease progression after 72.7 months of gefitinib therapy; rebiopsy was done, and next-generation sequencing showed the disappearance of the previous <italic>EGFR</italic> mutations. In addition, two new <italic>ALK</italic> fusions emerged, indicating that the emergence of dual ALK rearrangement may be the underlying mechanism of gefitinib resistance. The patient exhibits an excellent response to second-line alectinib treatment with a significant clinical benefit and a high quality of life. Finally, we summarized previous studies in which <italic>ALK</italic> fusion is a required resistance mechanism to EGFR-TKI.</p>