The novel combination of dual mTOR inhibitor AZD2014 and pan-PIM inhibitor AZD1208 inhibits growth in acute myeloid leukemia via HSF pathway suppression.

ABSTRACT: Mammalian target of rapamycin (mTOR) signaling is a critical pathway in the biology of acute myeloid leukemia (AML). Proviral integration site for moloney murine leukemia virus (PIM) serine/threonine kinase signaling takes part in various pathways exerting tumorigenic properties. We hypothesized that the combination of a PIM kinase inhibitor with an mTOR inhibitor might have complementary growth-inhibitory effects against AML. The simultaneous inhibition of the PIM kinase by pan-PIM inhibitor AZD1208 and of mTOR by selective mTORC1/2 dual inhibitor AZD2014 exerted anticancer properties in AML cell lines and in cells derived from primary AML samples with or without supportive stromal cell co-culture, leading to suppressed proliferation and increased apoptosis. The combination of AZD1208 and

SUBMITTER: Harada M 

PROVIDER: S-EPMC4741975 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature