Lapatinib Suppresses HER2-Overexpressed Cholangiocarcinoma and Overcomes ABCB1- Mediated Gemcitabine Chemoresistance.

ABSTRACT:

Background

Recent breakthroughs in cholangiocarcinoma (CCA) genomics have led to the discovery of many unique identifying mutations, of which HER2 has been found to be overexpressed specifically in cases of extrahepatic CCA. However, whether or not lapatinib (an oral tyrosine kinase inhibitor selective for inhibition of HER2), or a combination of lapatinib and gemcitabine, exerts inhibitory effects on HER2-overexpressed CCA is still unclear.

Methods

The effect of lapatinib and a lapatinib-gemcitabine combination treatment on CCA was determined using organoid and cell line models. Cell cycle arrest, apoptosis and proteins involving HER2-dependent downstream signaling pathways were analyzed to assess the effect of lapatinib on HER2⁺ CCA. The synergistic effect of la

SUBMITTER: Bai Z 

PROVIDER: S-EPMC9033256 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature