Laboratory of Tumor Biology, Department of Experimental Biology, Faculty of Science, Masaryk University, 61137 Brno, Czech Republic.
International Clinical Research Center, St. Anne's University Hospital, 65691 Brno, Czech Republic.
Int J Mol Sci. 2018 Jan 3;19(1):132. doi: 10.3390/ijms19010132.
Retinoids represent a popular group of differentiation inducers that are successfully used in oncology for treatment of acute promyelocytic leukemia in adults and of neuroblastoma in children. The therapeutic potential of retinoids is based on their key role in the regulation of cell differentiation, growth, and apoptosis, which provides a basis for their use both in cancer therapy and chemoprevention. Nevertheless, patients treated with retinoids often exhibit or develop resistance to this therapy. Although resistance to retinoids is commonly categorized as either acquired or intrinsic, resistance as a single phenotypic feature is usually based on the same mechanisms that are closely related or combined in both of these types. In this review, we summarize the most common changes in retinoid metabolism and action that may affect the sensitivity of a tumor cell to treatment with retinoids. The availability of retinoids can be regulated by alterations in retinol metabolism or in retinoid intracellular transport, by degradation of retinoids or by their efflux from the cell. Retinoid effects on gene expression can be regulated via retinoid receptors or via other molecules in the transcriptional complex. Finally, the role of small-molecular-weight inhibitors of altered cell signaling pathways in overcoming the resistance to retinoids is also suggested.
类视黄醇是一类分化诱导剂，在肿瘤学中广泛应用，可用于治疗成人急性早幼粒细胞白血病和儿童神经母细胞瘤。类视黄醇的治疗潜力基于其在细胞分化、生长和凋亡调控中的关键作用，这为其在癌症治疗和化学预防中的应用提供了基础。然而，接受类视黄醇治疗的患者常常表现出或发展出对此类治疗的耐药性。尽管类视黄醇耐药性通常分为获得性或固有性，但作为单一表型特征的耐药性通常基于这两种类型中密切相关或结合的相同机制。在这篇综述中，我们总结了可能影响肿瘤细胞对类视黄醇治疗敏感性的类视黄醇代谢和作用的最常见变化。视黄醇代谢或类视黄醇细胞内转运的改变、类视黄醇的降解或其从细胞中的流出可调节类视黄醇的可用性。视黄醇对基因表达的影响可通过视黄醇受体或转录复合物中的其他分子进行调节。最后，还提出了小分子细胞信号通路抑制剂在克服类视黄醇耐药性中的作用。
