Journal
PIGMENT CELL & MELANOMA RESEARCH
Volume 32, Issue 2, Pages 292-302Publisher
WILEY
DOI: 10.1111/pcmr.12742
Keywords
cholesterol; Hippo; melanoma; metabolism; statin
Categories
Funding
- NIH [T32GM007324]
- NCI [P50 CA121974]
- NRSA [1F30CA180591-01]
- American Skin Association
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This study evaluates the use of HMG-CoA reductase inhibitors, or statins, as an adjunctive to BRAF and MEK inhibition as a treatment in melanomas and other tumors with driver mutations in the MAPK pathway. Experiments used simvastatin in conjunction with vemurafenib and selumetinib in vitro and simvastatin with vemurafenib in vivo to demonstrate additional growth abrogation beyond MAPK blockade alone. Additional studies demonstrated that statin anti-tumor effects appeared to depend on inhibition of isoprenoid synthesis given rescue with add-back of downstream metabolites. Ultimately, we concluded that statins represent a possible useful adjunctive therapy in MAPK-driven tumors when given with current approved targeted therapy.
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