The HER2 inhibitor lapatinib potentiates doxorubicin-induced cardiotoxicity through iNOS signaling.

ABSTRACT: Rationale: Lapatinib (LAP) is a crucial alternative to trastuzumab upon the onset of drug resistance during treatment of metastatic human epidermal growth factor receptor 2-positive breast cancer. Like trastuzumab, LAP is commonly used alongside anthracyclines as a combination therapy, due to enhanced anti-cancer efficacy. However, this is notably associated with cardiotoxicity so it is imperative to understand the mechanisms driving this cardiotoxicity and develop cardioprotective strategies. To this end, here we utilize human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), which exhibit several characteristics representative of in vivo cardiomyocytes that make them breakthrough models to study drug toxicity. Methods: We investigated LAP- and doxorubicin (DOX

SUBMITTER: Hsu WT 

PROVIDER: S-EPMC6010982 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature