BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Activator protein-1 (AP-1; JUN)

September 24, 2015 7:00 AM UTC

In vitro and mouse studies suggest inhibiting AP-1 could help sensitize melanomas to BRAF inhibitors. In a panel of BRAF-mutant melanoma cell lines, resistance to the BRAF inhibitors Zelboraf vemurafenib or Tafinlar dabrafenib was associated with expression of AP-1 and an invasive mesenchymal phenotype. In drug-sensitive melanoma cell lines and tumor samples from patients, AP-1 mRNA levels were higher after treatment with a BRAF inhibitor than before. In drug-resistant, BRAF-mutant melanoma cell lines, Zelboraf plus an inhibitor of AP-1 phosphorylation or siRNA targeting AP-1 increased cell death compared with Zelboraf alone. Next steps could include testing the combination of Zelboraf and AP-1 inhibition in additional cancer models.

Daiichi Sankyo Co. Ltd., Chugai Pharmaceutical Co. Ltd. and Roche market Zelboraf to treat melanoma...