Therapeutics: Yes-associated protein 1 (YAP1; YAP)

Studies in cell culture, mice and patient samples suggest inhibiting YAP1 could help treat cancer by sensitizing tumors to BRAF and MEK inhibitors. In human non-small cell lung cancer (NSCLC) cells that express the V600E BRAF mutation, shRNA knockdown of YAP1 increased sensitivity to either BRAF inhibitor Zelboraf vemurafenib or MEK inhibitor Mekinist trametinib compared with scrambled shRNA. In a mouse xenograft model of melanoma, shRNA knockdown of YAP1 decreased tumor growth resulting from Zelboraf or Mekinist therapy compared with scrambled shRNA. In patients with V600E mutant BRAF melanoma, low YAP1 expression was associated with response to various BRAF and MEK inhibitors. Next steps include exploring the crosstalk between the YAP1 and MAP kinase pathways and strategies to target YAP1 therapeutically.

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