Combined CDK4/6 and Pan-mTOR Inhibition Is Synergistic Against Intrahepatic Cholangiocarcinoma.

ABSTRACT:

Purpose

Intrahepatic cholangiocarcinoma (ICC) is an aggressive cancer type, lacking effective therapies and associated with a dismal prognosis. Palbociclib is a selective CDK4/6 inhibitor, which has been shown to suppress cell proliferation in many experimental cancer models. Recently, we demonstrated that pan-mTOR inhibitors, such as MLN0128, effectively induce apoptosis, although have limited efficacy in restraining proliferation of ICC cells. Here, we tested the hypothesis that palbociclib, due to its antproliferative properties in many cancer types, might synergize with MLN0128 to impair ICC growth.

Experimental design

Human ICC cell lines and the AKT/YapS127A ICC mouse model were used to test the therapeutic efficacy of palbociclib and MLN0128, either alone or in combin

SUBMITTER: Song X 

PROVIDER: S-EPMC6423983 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature