维生素A衍生物维甲酸（RA）是一种重要代谢物。RA在发育过程中发挥着重要作用，有利于胚胎发育和细胞分化。机制上，RA结合到其特定的核受体，包括维甲酸受体和视黄酸X受体，从而触发基因转录，并导致基因调控的进一步后果。这种功能性异二聚体的激活随后会导致基因的激活/失活。已经发表了几篇与维甲酸详细的胚胎和发育作用以及作为特定癌症的抗癌药物相关的报告，包括急性早幼粒白血病、乳腺癌和前列腺癌。然而，反全反式维甲酸（ATRA）的其他方面尚未广泛研究。在本综述中，我们着重讨论了RA途径的作用和其下游基因激活与癌症进展的关系。此外，我们还通过重点关注醛脱氢酶（ALDH）家族酶的双重作用，探讨了靶向维甲酸途径的方法。将RA靶点与ALDH特异性靶点相结合的组合策略使肿瘤细胞对治疗敏感，并提高患者的无进展生存期。除了ATRA的基因组效应，我们还强调了ATRA在非经典机制中作为免疫检查点抑制剂的作用，从而针对当前时代癌症治疗的免疫肿瘤学角度。本综述还阐述了ATRA在激活独立机制方面的作用。本综述还重点介绍了ATRA与其他化疗药物联合治疗的当前临床试验，并解释了与ATRA使用有关的未来方向性见解。版权所有 © 2023 Lavudi, Nuguri, Olverson, Dhanabalan, Patnaik and Kokkanti.

Retinoic acid (RA) is a vital metabolite derived from vitamin A. RA plays a prominent role during development, which helps in embryological advancement and cellular differentiation. Mechanistically, RA binds to its definite nuclear receptors including the retinoic acid receptor and retinoid X receptor, thus triggering gene transcription and further consequences in gene regulation. This functional heterodimer activation later results in gene activation/inactivation. Several reports have been published related to the detailed embryonic and developmental role of retinoic acids and as an anti-cancer drug for specific cancers, including acute promyelocytic leukemia, breast cancer, and prostate cancer. Nonetheless, the other side of all-trans retinoic acid (ATRA) has not been explored widely yet. In this review, we focused on the role of the RA pathway and its downstream gene activation in relation to cancer progression. Furthermore, we explored the ways of targeting the retinoic acid pathway by focusing on the dual role of aldehyde dehydrogenase (ALDH) family enzymes. Combination strategies by combining RA targets with ALDH-specific targets make the tumor cells sensitive to the treatment and improve the progression-free survival of the patients. In addition to the genomic effects of ATRA, we also highlighted the role of ATRA in non-canonical mechanisms as an immune checkpoint inhibitor, thus targeting the immune oncological perspective of cancer treatments in the current era. The role of ATRA in activating independent mechanisms is also explained in this review. This review also highlights the current clinical trials of ATRA in combination with other chemotherapeutic drugs and explains the future directional insights related to ATRA usage.Copyright © 2023 Lavudi, Nuguri, Olverson, Dhanabalan, Patnaik and Kokkanti.