Papa Anselmo, Zaccarelli Eleonora, Caruso Davide, Vici Patrizia, Benedetti Panici Pierluigi, Tomao Federica
a Department of Medico-Surgical Sciences and Biotechnologies, "Sapienza" University of Rome, Oncology Unit , Istituto Chirurgico Ortopedico Traumatologico , 04100 Latina , Italy.
b Division of Medical Oncology B , Regina Elena National Cancer Institute , 00144 Rome , Italy.
Expert Opin Investig Drugs. 2016;25(1):31-49. doi: 10.1517/13543784.2016.1116517. Epub 2015 Dec 19.
Endometrial carcinoma represents the most frequent gynecologic tumor in developed countries. The majority of women presents with low-grade tumors but a significant subset of women experience recurrence and do not survive their disease. Patients with stage III/ IV or recurrent endometrial cancer have a poor prognosis. Identification of active and tolerable new targeted agents versus specific molecular targets is a priority objective. Angiogenesis is a complex process that plays a crucial role in the development of many types of cancer and in particular endometrial cancer.
In this review, the authors highlight the main angiogenetic molecular pathways and the anti-angiogenic agents in Phase II clinical trials for endometrial cancer treatment. The authors focus on reports from recent years on angiogenesis inhibitors used in endometrial cancer, including anti- vascular endothelial growth factor (VEGF) monoclonal antibodies (bevacizumab and aflibercept), mammalian target of rapamycin inhibitors (mTORi) (everolimus, temsirolimus and ridaforolimus), PI3 K inhibitors (BKM120), tyrosine kinase inhibitors (brivanib, sunitinib, dovitinib and nintedanib) and thalidomide.
These anti-angiogenic drugs, while used either alone or in combination with chemotherapy, have presented mixed results in treating endometrial cancer patients. Challenges for the future include the identification of new pathways, early identification and overcoming resistance and the use of these molecules in combination with old and new chemotherapeutic and targeted agents.
子宫内膜癌是发达国家最常见的妇科肿瘤。大多数女性患的是低级别肿瘤，但有相当一部分女性会复发且无法战胜疾病。III/IV期或复发性子宫内膜癌患者预后较差。识别针对特定分子靶点的有效且耐受性良好的新型靶向药物是首要目标。血管生成是一个复杂的过程，在多种癌症尤其是子宫内膜癌的发展中起着关键作用。
在本综述中，作者重点介绍了子宫内膜癌治疗II期临床试验中的主要血管生成分子途径和抗血管生成药物。作者关注近年来有关子宫内膜癌中使用的血管生成抑制剂的报告，包括抗血管内皮生长因子（VEGF）单克隆抗体（贝伐单抗和阿柏西普）、雷帕霉素靶蛋白抑制剂（mTORi）（依维莫司、替西罗莫司和利达罗莫司）、PI3K抑制剂（BKM120）、酪氨酸激酶抑制剂（布立尼布、舒尼替尼、多韦替尼和尼达尼布）以及沙利度胺。
这些抗血管生成药物，无论是单独使用还是与化疗联合使用，在治疗子宫内膜癌患者时都呈现出喜忧参半的结果。未来的挑战包括识别新途径、早期识别并克服耐药性以及将这些分子与新旧化疗药物和靶向药物联合使用。
