Focal adhesion kinase activation limits efficacy of Dasatinib in c-Myc driven hepatocellular carcinoma.

ABSTRACT: Hepatocellular carcinoma (HCC) is a deadly malignancy with limited treatment options. Recently, it was found that Dasatinib treatment led to synthetic lethality in c-Myc high-expressing human cancer cells due to inhibition of p-Lyn. Overexpression of c-Myc is frequently seen in human HCC. We investigated the sensitivity to Dasatinib in vitro using HCC cell lines and in vivo using c-Myc mouse HCC model. We found that HCC cell line responsiveness to Dasatinib varied significantly. However, there was no correlation between c-Myc expression and IC₅₀ to Dasatinib. In c-Myc-induced HCC in mice, tumors continued to grow despite Dasatinib treatment, although the eventual tumor burden was lower in Dasatinib treatment cohort. Molecular analyses revealed that Dasatinib was effective in inh

SUBMITTER: Liu X 

PROVIDER: S-EPMC6308083 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature