Natural and synthetic retinoids in preclinical colorectal cancer models

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide. Although targeted therapy in combination with chemotherapy in CRC prolongs the overall survival of patients with metastatic disease, acquired resistance and relapse hinder their clinical benefits. Moreover, patients with some specific genetic profile are unlikely to benefit from targeted therapy, suggesting the need for safe and effective treatment strategies. Retinoids, comprising of natural and synthetic analogs, are a class of chemical compounds that regulate cellular proliferation, differentiation, and cell death. Retinoids have been used in the clinic for several leukemias and solid tumors, either as single agents or in combination therapy. Furthermore, retinoids have shown potent chemotherapeutic and chemopreventive properties in different cancer models, including CRC. In this review, we summarize the major preclinical findings in CRC in which natural and synthetic retinoids showed promising antitumor activities and stress on the proposed mechanisms of action. Understanding of the retinoids' antitumor mechanisms would provide insights to support and warrant their development in the management of CRC.