BioCentury
ARTICLE | Distillery Therapeutics

Therapeutics: Aldehyde dehydrogenase 1 family member A1 (ALDH1A1); cytochrome P450 26A1 (CYP26A1; CP26)

September 22, 2016 7:00 AM UTC

Patient sample and mouse studies suggest enhancing all-trans retinoic acid (ATRA) levels could help treat colorectal cancer. In tumor samples from colorectal cancer patients, levels of ALDH1A1 - which participates in the biosynthesis of ATRA - were lower, and levels of CYP26A1- which catabolizes ATRA - were higher than in normal colonic tissue samples, and low tumor CYP26A1 levels correlated with survival. In a mouse model of colorectal cancer, the generic antibiotics ampicillin, metronidazole, vancomycin or neomycin increased ALDH1A1 expression and decreased CYP26A1 expression and tumor growth compared with vehicle. Also in the model, ATRA or a pan-CYP26A1 inhibitor tool compound decreased tumor growth. In a second mouse model of colorectal cancer, ATRA decreased tumor growth. Next steps include testing ATRA and inhibitors of ATRA metabolism in animal models of metastatic colorectal cancer.

The generic ATRA is marketed for acne, other skin conditions and acute promyelocytic leukemia (APL)...