Department of Obstetrics and Gynecology, Tottori University School of Medicine, 36-1 Nishicho, Yonago 683-8504, Japan.
Int J Clin Oncol. 2012 Oct;17(5):430-40. doi: 10.1007/s10147-012-0459-8. Epub 2012 Aug 28.
Ovarian cancer is the leading cause of death in women with gynecological cancer. Most patients are diagnosed at an advanced stage with a poor prognosis. Currently, surgical tumor debulking followed by chemotherapy based on platinum and taxane is the standard treatment for advanced disease. However, these patients remain at great risk for recurrence and developing drug resistance. Therefore, new treatment strategies are needed to improve outcomes for patients with advanced and recurrent ovarian cancer. Several agents targeted at particular molecules have been developed for ovarian cancer and are now entering clinical trials. The functional targets of these agents are aberrations in tumor tissues including angiogenesis, the human epidermal growth factor receptor family, poly(ADP-ribose) polymerase (PARP), mammalian target of rapamycin (mTOR) signaling pathway, and α-folate receptor (α-FR). The anti-angiogenic compound bevacizumab has been reported as the most effective targeted agent. Bevacizumab plus chemotherapy prolonged progression-free survival (PFS) both for advanced and platinum-sensitive recurrent ovarian cancer, but did not increase overall survival. A PARP inhibitor, olaparib, applied as maintenance treatment also improved PFS in platinum-sensitive relapsed ovarian cancer. Furthermore, mTOR inhibitors and a monoclonal antibody to α-FR, farletuzumab, are attractive treatment strategies either alone or combined with chemotherapy. Understanding the tumor molecular biology and identifying predictive biomarkers are essential steps in selecting the best treatment strategies. This article reviews available clinical data on the most promising targeted agents for ovarian cancer.
卵巢癌是妇科癌症患者死亡的主要原因。大多数患者在晚期被诊断出，预后较差。目前，手术肿瘤减灭术联合基于铂类和紫杉烷类的化疗是晚期疾病的标准治疗方法。然而，这些患者仍然存在很大的复发和耐药风险。因此，需要新的治疗策略来改善晚期和复发性卵巢癌患者的预后。已经开发了几种针对特定分子的药物用于卵巢癌，目前正在进行临床试验。这些药物的功能靶点是肿瘤组织中的异常，包括血管生成、人表皮生长因子受体家族、多聚（ADP-核糖）聚合酶（PARP）、哺乳动物雷帕霉素靶蛋白（mTOR）信号通路和α-叶酸受体（α-FR）。抗血管生成化合物贝伐珠单抗已被报道为最有效的靶向药物。贝伐珠单抗联合化疗延长了晚期和铂类敏感复发性卵巢癌的无进展生存期（PFS），但并未增加总生存期。PARP 抑制剂奥拉帕利作为维持治疗也改善了铂类敏感复发性卵巢癌的 PFS。此外，mTOR 抑制剂和针对 α-FR 的单克隆抗体 farletuzumab 是单独或联合化疗的有吸引力的治疗策略。了解肿瘤分子生物学并确定预测生物标志物是选择最佳治疗策略的关键步骤。本文综述了卵巢癌最有前途的靶向药物的临床数据。
