Parisotto Maxime, Brodeur Hélène, Bhat Pangala V, Mader Sylvie
Département de biochimie et Institut de recherche en immunologie et cancérologie, Université de Montréal, CP 6128, succursale Centre-ville, Montréal (Québec), H3C 3J7 Canada.
Med Sci (Paris). 2006 Dec;22(12):1101-6. doi: 10.1051/medsci/200622121101.
Retinoids play important roles in cell differentiation and apoptosis, notably in epithelial tissues. Their utility in cancer therapy has been demonstrated in specific cancer types. Use of retinoic acid (RA) in the treatment of acute promyelocytic leukemia was the first successful example of retinoid-based differentiation therapy. RA has since been evaluated for treatment of other cancers, revealing variable effectiveness. The observation that expression of enzymes involved in RA biosynthesis is suppressed during tumorigenesis suggests that intra-tumor depletion in RA levels may contribute to tumor development and argues for the use of retinoids in cancer treatment. However, the induction of RA-inactivating enzymes is one of the mechanisms that may limit the efficacy of retinoid therapy and contribute to acquired resistance to RA treatment, suggesting that retinoic acid metabolism blocking agents may be effective agents in differentiation therapy.
维甲酸在细胞分化和凋亡中发挥着重要作用,尤其是在上皮组织中。它们在特定癌症类型的治疗中的效用已得到证实。维甲酸(RA)用于治疗急性早幼粒细胞白血病是基于维甲酸的分化疗法的首个成功范例。此后,人们对RA治疗其他癌症进行了评估,结果显示其疗效各异。肿瘤发生过程中参与RA生物合成的酶的表达受到抑制这一观察结果表明,肿瘤内RA水平的降低可能有助于肿瘤发展,这为在癌症治疗中使用维甲酸提供了依据。然而,RA失活酶的诱导是可能限制维甲酸疗法疗效并导致对RA治疗产生获得性耐药的机制之一,这表明维甲酸代谢阻断剂可能是分化疗法中的有效药物。