IRCCS MultiMedica, Milan, Italy.
Crit Rev Oncol Hematol. 2010 Jul;75(1):2-14. doi: 10.1016/j.critrevonc.2009.10.007. Epub 2010 Jan 19.
Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic "angiopreventive" properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients.
临床试验表明，N-(4-羟基苯基)维 A 酰胺（4HPR；芬维 A 胺），一种合成维 A 酸衍生物，是一种高效且有前途的治疗和化学预防药物。芬维 A 胺在体外和临床前研究中对多种癌症类型具有生物活性。临床试验表明，芬维 A 胺可显著降低绝经前妇女的第二乳腺癌风险。目前正在进行多项针对不同肿瘤的研究，如乳腺癌和卵巢癌、神经母细胞瘤、胶质母细胞瘤、头颈部和皮肤癌等。它在人类中的副作用极小，因此可以考虑在高乳腺癌和卵巢癌风险的年轻女性中进行试验，以及预防其他肿瘤类型，如肺癌。在这里，我们回顾了一些正在进行的临床试验，并评估了 4HPR 发挥次级化学预防作用的可能机制。特别是，我们报告了关于芬维 A 胺的抗血管生成“血管预防”特性、其抗侵袭活性、诱导细胞凋亡以及产生或增强活性氧产生的基础和转化数据，作为患者化学预防作用的可能分子基础。
