Reprofiling using a zebrafish melanoma model reveals drugs cooperating with targeted therapeutics.

ABSTRACT: Phenotype-guided re-profiling of approved drug molecules presents an accelerated route to developing anticancer therapeutics by bypassing the target-identification bottleneck of target-based approaches and by sampling drugs already in the clinic. Further, combinations incorporating targeted therapies can be screened for both efficacy and toxicity. Previously we have developed an oncogenic-RAS-driven zebrafish melanoma model that we now describe display melanocyte hyperplasia while still embryos. Having devised a rapid method for quantifying melanocyte burden, we show that this phenotype can be chemically suppressed by incubating V12RAS transgenic embryos with potent and selective small molecule inhibitors of either MEK or PI3K/mTOR. Moreover, we demonstrate that combining MEK inhibitors (M

SUBMITTER: Fernandez Del Ama L 

PROVIDER: S-EPMC5130012 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature