Bollag W, Holdener E E
Department of Clinical Research, F Hoffmann-La Roche Ltd, Basel, Switzerland.
Ann Oncol. 1992 Jul;3(7):513-26. doi: 10.1093/oxfordjournals.annonc.a058252.
Retinoids are a class of compounds structurally related to vitamin A. In preclinical studies, all-trans retinoic acid (tretinoin), 13-cis retinoic acid (isotretinoin) and the aromatic retinoids etretinate and acitretin have preventive and therapeutic effects on carcinogen-induced premalignant and malignant lesions. Clinically, chemoprevention with isotretinoin and etretinate has been tested with some degree of success in such indications as basal cell carcinomas, squamous cell carcinomas, superficial bladder tumors and second primary tumors in patients with squamous cell carcinoma of the head and neck. Limited therapeutic success has also been achieved with retinoid treatment of precancerous and cancerous conditions of the skin, oral cavity, larynx, lung, bladder and vulva. Dramatic therapeutic effects have been observed in the treatment of acute promyelocytic leukemia with tretinoin, which leads to very high rate of complete remission. Excellent results were recently reported in the treatment of squamous cell carcinomas of the skin and cervix with a combination of isotretinoin and recombinant interferon alfa-2a (rIFN alfa-2a, Roferon-A). The mechanism of action of retinoids is through modulation of cell proliferation and differentiation. Retinoids vary in their capacity to induce differentiation and to inhibit proliferation in a series of human transformed hematopoietic and epithelial cell lines. Some cytokines potentiate the retinoid-induced cell differentiation and act synergistically with retinoids to inhibit cell proliferation. The pattern of synergism is dependent upon the combination and tumor cell line tested. The discovery of nuclear retinoid receptors has contributed substantially to the understanding of the mechanism of action of retinoids at the molecular level. Further understanding of the molecular biology of retinoids is expected to contribute to a rational design of new retinoids in the future, which in turn may result in improvements in the prevention and therapy of cancer.
维甲酸是一类在结构上与维生素A相关的化合物。在临床前研究中，全反式维甲酸（维甲酸）、13 - 顺式维甲酸（异维甲酸）以及芳香族维甲酸依曲替酯和阿维A对致癌物诱导的癌前病变和恶性病变具有预防和治疗作用。临床上，异维甲酸和依曲替酯的化学预防在基底细胞癌、鳞状细胞癌、浅表膀胱肿瘤以及头颈部鳞状细胞癌患者的第二原发性肿瘤等适应症中已进行了测试，并取得了一定程度的成功。维甲酸治疗皮肤、口腔、喉、肺、膀胱和外阴的癌前和癌性疾病也取得了有限的治疗成功。维甲酸治疗急性早幼粒细胞白血病已观察到显著的治疗效果，可导致很高的完全缓解率。最近有报道称，异维甲酸与重组干扰素α - 2a（rIFNα - 2a，罗扰素）联合治疗皮肤和宫颈癌取得了优异的效果。维甲酸的作用机制是通过调节细胞增殖和分化。在一系列人类转化造血和上皮细胞系中，维甲酸诱导分化和抑制增殖的能力各不相同。一些细胞因子可增强维甲酸诱导的细胞分化，并与维甲酸协同作用以抑制细胞增殖。协同作用模式取决于所测试的组合和肿瘤细胞系。核维甲酸受体的发现极大地促进了在分子水平上对维甲酸作用机制的理解。对维甲酸分子生物学的进一步理解有望在未来有助于合理设计新的维甲酸，进而可能改善癌症的预防和治疗。
