MIG6 Mediates Adaptive and Acquired Resistance to ALK/ROS1 Fusion Kinase Inhibition through EGFR Bypass Signaling.

ABSTRACT: Despite the initial benefit from tyrosine kinase inhibitors (TKI) targeting oncogenic ALK and ROS1 gene fusions in non-small cell lung cancer, complete responses are rare and resistance ultimately emerges from residual tumor cells. Although several acquired resistance mechanisms have been reported at the time of disease progression, adaptative resistance mechanisms that contribute to residual diseases before the outgrowth of tumor cells with acquired resistance are less clear. For the patients who have progressed after TKI treatments, but do not demonstrate ALK/ROS1 kinase mutations, there is a lack of biomarkers to guide effective treatments. Herein, we found that phosphorylation of MIG6, encoded by the ERRFI1 gene, was downregulated by ALK/ROS1 inhibitors as were mRNA levels, thus potent

SUBMITTER: Chen N 

PROVIDER: S-EPMC10762338 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature