Novel NOTCH2-NTRK1 fusion confers osimertinib resistance in EGFR-mutant non-small cell lung cancer by interacting with EGFR.

ABSTRACT:

Background

Overcoming osimertinib resistance in epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) is challenging due to unclear mechanisms. We previously reported a NSCLC case with EGFR mutations progressed on osimertinib therapy, revealing a novel NOTCH2-NTRK1 fusion gene in the plasma and tumor tissue. Although the NTRK gene fusion has been identified in NSCLC and a range of tumor types, the role of NOTCH2-NTRK1 in osimertinib resistance is unclear.

Methods

We utilized both in vitro and in vivo models exhibiting NOTCH2-NTRK1 fusion positivity to explore the biological function of NOTCH2-NTRK1, as well as its role and mechanism in osimertinib resistance.

Results

The NOTCH2-NTRK1 fusion protein has been demonstrated to transform the hum

SUBMITTER: Li H 

PROVIDER: S-EPMC12686637 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature