BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Heat shock protein 90 (Hsp90); transcription factor A mitochondrial (TFAM; TCF6)

May 12, 2016 7:00 AM UTC

Cell culture and mouse studies suggest inhibiting mitochondrial Hsp90 or TFAM could help treat BRAF-mutant melanoma resistant to MAP kinase inhibitors. In a BRAF-mutant human melanoma cell line resistant to MAP kinase inhibitors, knockdown of mitochondrial Hsp90 or TFAM plus a BRAF inhibitor tool compound and a MEK inhibitor tool compound increased cell death compared with normal mitochondrial expression of Hsp90 and TFAM plus the two inhibitors. Also in the cell line, the mitochondrial Hsp90 inhibitor gamitrinib plus the BRAF inhibitor increased cell death compared with the BRAF inhibitor alone. In two xenograft mouse models of BRAF-mutant MAP kinase inhibitor-resistant melanoma, gamitrinib plus the BRAF inhibitor decreased tumor growth. Next steps could include testing inhibitors of mitochondrial Hsp90 or TFAM in other models of cancer...