Synergistic Activity of the HSP90 Inhibitor Ganetespib With Lapatinib Reverses Acquired Lapatinib Resistance in HER2-Positive Breast Cancer Cells.

ABSTRACT: Lapatinib is an FDA-approved EGFR and HER2 tyrosine kinase inhibitor for the treatment of HER2-positive breast cancer patients. However, its therapeutic efficacy is limited by primary or acquired resistance. In the present study, we established breast cancers cells with acquired lapatinib resistance and investigated the antitumor activity of the second-generation HSP90 inhibitor ganetespib in association with lapatinib in lapatinib-sensitive and -resistant cells. The combination treatment showed synergistic inhibition of HER and the downstream PI3K/Akt and Ras/MEK/ERK pathways, in addition to enhancing induction of early apoptotic cell death and G1 arrest in both parent and lapatinib-resistant cells in vitro. The joint administration of ganetespib and lapatinib depleted the aberrant

SUBMITTER: Ye M 

PROVIDER: S-EPMC8287059 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature