BioCentury
ARTICLE | Distillery Therapeutics

Cancer

January 25, 2017 10:47 PM UTC

Patient sample, cell culture and mouse studies suggest inhibiting the GCCR-YAP1 signaling axis could help treat breast cancer. In patients, high GCCR signaling activity in tumors was associated with high YAP1 levels in tumors and poor metastasis-free survival. In a Ras-transformed, corticosteroid-stimulated human mammary epithelial cell line, knockdown of YAP1 decreased tumorsphere formation compared with normal YAP1 expression. In a corticosteroid-stimulated triple-negative breast cancer (TNBC) cell line, the generic chemotherapy paclitaxel plus a GCCR inhibitor tool compound decreased tumorsphere formation compared with either agent alone, and the GCCR inhibitor or the YAP1 inhibitor Visudyne verteporfin decreased tumorsphere formation compared with vehicle. In a xenograft mouse model of breast cancer, tumor-specific knockdown of GCCR decreased tumor levels of YAP1, tumor size and tumor engraftment compared with normal GCCR expression. Next steps include clinical testing of GCCR signaling inhibitors.

Valeant Pharmaceuticals International Inc. and Novartis AG market Visudyne, a light-activated benzoporphyrin derivative used in photodynamic therapy (PDT), to treat choroidal neovascularization (CNV)...