Individualized strategies to target specific mechanisms of disease in malignant melanoma patients displaying unique mutational signatures.

ABSTRACT: Targeted treatment of advanced melanoma could benefit from the precise molecular characterization of melanoma samples. Using a melanoma-specific selection of 217 genes, we performed targeted deep sequencing of a series of biopsies, from advanced melanoma cases, with a Breslow index of ≥ 4 mm, and/or with a loco-regional infiltration in lymph nodes or presenting distant metastasis, as well of a collection of human cell lines. This approach detected 3-4 mutations per case, constituting unique mutational signatures associated with specific inhibitor sensitivity. Functionally, case-specific combinations of inhibitors that simultaneously targeted MAPK-dependent and MAPK-independent mechanisms were most effective at inhibiting melanoma growth, against each specific mutational background. These o

SUBMITTER: Curiel-Olmo S 

PROVIDER: S-EPMC4694844 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature