**1. Introduction**

Our goal herein is to review current research findings on retinoids in colorectal cancer (CRC), and to provide an update from our bioinformatics analysis of RA signaling components in CRC. Retinoic acid (RA) is currently being used in the treatment of specific types of human cancers [1]. The classic example is use of ATRA as first line treatment for acute promyelocytic leukemia (APL). RA therapy has also been shown to improve survival in patients with neuroblastoma [2–4]. Additionally, RA-based agents have been evaluated for clinical anti-cancer activity in breast cancer and in lung cancer [5]. In this review, we discuss the anti-cancer activity of retinoids using *in vitro* and *in vivo* models of CRC, and the use of ATRA as a differentiation agent in SC research [4, 6–8].

A strong rationale to investigate RA signaling in oncology research is that ATRA is an effective drug used to treat APL patients. Indeed, ATRA effectively induces APL cells to terminally differentiate into neutrophils [9–11]. Current treatment regimens for APL also include arsenic in combination with ATRA because the combination provides a synergic drug response that cures the majority of APL patients, who

would otherwise be facing a highly fatal illness. The precise mechanism involved in triggering APL cells have been extensively studied with the hope of understanding how it can be applied to trigger differentiation in other cancer types. What appears to be the basis for clinical success in treating APL is that the RA/arsenic combination not only induces terminal differentiation, but it also abrogates self-renewal of APL SCs [12]. Thus, future retinoid-based treatments for other cancers will likely necessitate drug combinations that incorporate a RA signaling differentiation therapy and a SC-targeting therapy that inhibits cancer SC self-renewal.
