Activation of the AKT-mTOR pathway confers selpercatinib resistance in thyroid cancer cells harboring the <i>CCDC6-RET</i> fusion gene.

ABSTRACT: Treatment strategies based on genetic alterations have been recently developed for the treatment of advanced or metastatic thyroid cancer. RET inhibitors are used to treat thyroid cancer with rearranged during transfection (RET) gene alterations; however, the emergence of drug resistance challenges effective treatment. Therefore, we aimed to elucidate the mechanisms underlying resistance to the RET inhibitor, selpercatinib. We used the papillary carcinoma cell lines, TPC-1 and CUTC48, which harbor the CCDC6-RET fusion gene. We established a selpercatinib-resistant subline (TPC-1/SELR) in TPC-1 via long-term exposure to selpercatinib. The growth-inhibitory effects of the drugs were analyzed using the WST assay. Changes in intracellular signal transduction were analyzed using w

SUBMITTER: Amitani M 

PROVIDER: S-EPMC12272592 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature