Retinoids in Treatment of Colorectal Cancer

Retinoids are vitamin A metabolites best known for their role in embryonic development. Indeed, retinoid acid (RA) signaling plays a key role in regulating the development of the embryo body-plan by controlling embryonic stem cells (SCs). Retinoids function through their ability to induce cellular differentiation. Mutations in RA signaling pathway genes occur in most human cancers. The classic example is the chromosomal translocation involving RA receptor alpha in acute promyelocytic leukemia (APL). Because all-trans retinoic acid (ATRA) is a highly effective and often curative treatment for APL patients, determining if retinoids are efficacious for other cancer types is imperative. We review the current research on retinoids in colorectal cancer (CRC) and provide bioinformatics analyses of RA signaling. Our results show that most RA pathway genes are overexpressed and often mutated in CRC. Moreover, aberrant expression of many RA signaling proteins predicts decreased CRC patient survival. We also review aldehyde dehydrogenase (ALDH) expression in CRC because ALDH is a key enzyme in RA signaling, which regulates colonic SCs. Further investigation of RA signaling mechanisms that regulate colon SCs and how dysregulation contributes to the SC overpopulation that drives CRC growth should provide insight into strategies for designing new SC-targeted therapies for CRC.