Drug responses are conserved across patient-derived xenograft models of melanoma leading to identification of novel drug combination therapies.

ABSTRACT:

Background

Patient-derived xenograft (PDX) mouse tumour models can predict response to therapy in patients. Predictions made from PDX cultures (PDXC) would allow for more rapid and comprehensive evaluation of potential treatment options for patients, including drug combinations.

Methods

We developed a PDX library of BRAF-mutant metastatic melanoma, and a high-throughput drug-screening (HTDS) platform utilising clinically relevant drug exposures. We then evaluated 34 antitumor agents across eight melanoma PDXCs, compared drug response to BRAF and MEK inhibitors alone or in combination with PDXC and the corresponding PDX, and investigated novel drug combinations targeting BRAF inhibitor-resistant melanoma.

Results

The concordance of cancer-driving mutations across patie

SUBMITTER: Ice RJ 

PROVIDER: S-EPMC7054294 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature