BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Cytochrome P450 3A5 (CYP3A5)

March 24, 2016 7:00 AM UTC

Patient sample and mouse studies suggest inhibiting CYP3A5 could help treat drug-resistant pancreatic ductal adenocarcinoma (PDAC). In patient-derived PDAC cell lines, high expression of CYP3A5 in one cell subtype was associated with insensitivity to Tarceva erlotinib, Sprycel dasatinib or paclitaxel, and high expression of CYP3A5 in two other cell subtypes was associated with acquired resistance to paclitaxel. In the first subtype, shRNA targeting CYP3A5 increased sensitivity to Tarceva, Sprycel or paclitaxel compared with scrambled control shRNA. In the other two PDAC cell subtypes with acquired resistance to paclitaxel, CYP3A5 knockout increased sensitivity to the drug compared with normal CYP3A5 expression. Next steps could include testing CYP3A5 inhibition in other cancer types that are resistant to tyrosine kinase inhibitors or paclitaxel.

Astellas Pharma Inc., Chugai Pharmaceutical Co. Ltd. and Roche market Tarceva, a small molecule inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase activity, to treat pancreatic cancer and non-small cell lung cancer (NSCLC) and have the compound approved to treat brain cancer and in Phase III testing to treat liver cancer...