Synergistic anti-tumor activity by association of MEK and PI3K/mTOR blockade with TRAIL in human melanoma

ABSTRACT: Combining direct anti-tumor effects with targeting of tumor microenvironment is an attractive strategy that may lead to more effective therapies for advanced melanoma. Here, we tested whether association of TRAIL with co-targeting of MEK and PI3K/mTOR, or with MEK blockade, could have synergistic anti-melanoma activity mediated not only by induction of tumor cell death, but also by effects on the tumor microenvironment. Drug interaction analysis by the Chou-Talalay approach in a panel of 21 melanoma cell lines indicated that strong synergism could be achieved by association of the MEK1/2 inhibitor AZD6244, the PI3K/mTOR inhibitor NPV-BEZ235 and TRAIL, as well as by the AZD6244/TRAIL combination. Synergism was observed on most tumors including TRAIL- or inhibitor-resistant melanomas, irr

ORGANISM(S): Homo sapiens

SUBMITTER: Grazia G 

PROVIDER: S-ECPF-GEOD-55050 | biostudies-other | 2014

REPOSITORIES: biostudies-other