Modeling acquired TKI resistance and effective combination therapeutic strategies in murine RET+ lung adenocarcinoma.

ABSTRACT: RET gene rearrangements yield oncogenic fusion proteins that drive a subset of lung adenocarcinomas (LUAD). The tyrosine kinase inhibitors (TKIs) selpercatinib and pralsetinib are approved therapies for RET+ lung cancers and have markedly improved clinical outcomes in these patients, but acquired resistance remains a hurdle to their durable management. Using a recently developed murine model of RET+ lung cancer driven by a Trim24-Ret fusion protein, two Trim24-Ret cell lines (TR.1 and TR.2) were established. Orthotopic lung tumors generated by transplantation of these cell lines initially respond to selpercatinib followed by prompt progression within ~3 weeks of initiating TKI treatment. Cell lines derived from the selpercatinib-resistant TR.1 and TR.2 tumors exhibited in

SUBMITTER: Hinz TK 

PROVIDER: S-EPMC12157539 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature