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通往卵巢癌治疗策略性靶向的道路。

Roads to the strategic targeting of ovarian cancer treatment.

机构信息

Laboratorio de Fisiología y Biología tumoral del Ovario, Instituto de Biología y Medicina Experimental (IByME-CONICET), Buenos Aires, Argentina.

出版信息

Reproduction. 2021 Jan;161(1):R1-R11. doi: 10.1530/REP-19-0593.

Abstract

Although ovarian cancer mortality rates have slightly declined in the last 40 years, ovarian cancer continues to be the eighth cause of cancer death in women. Ovarian cancer is characterized by its high response to treatments but also by its high rate of recurrence. Although treatments are limited to cytoreductive surgery and platinum-based chemotherapy, other therapies using antiangiogenic agents and poly (ADP-ribose) polymerase inhibitors are being tested. Nevertheless, these therapeutic strategies have had poor results and new potential targets and approaches are thus needed. The present review focuses on the recent evidence on antiangiogenic strategies in ovarian cancer cells and on the mechanisms governed by Notch and β-catenin proteins. It also describes the concept of 'vascular normalization' by using the platelet-derived growth factor, PDGFB, molecule as a tool to regulate ovarian tumor angiogenesis and thus improve ovarian tumor treatment. It has been reported that alterations in the Notch system components and changes in the canonical Wnt/β-catenin signaling, the other pathway of our interest, are relevant to molecular events that contribute to ovarian cancer development. Thus, in this review, we consider these aspects of the ovarian tumor biology as potential new therapeutic strategies for the treatment of this disease.

摘要

尽管在过去的 40 年中,卵巢癌的死亡率略有下降,但它仍是女性癌症死亡的第八大原因。卵巢癌的特点是对治疗有高度反应,但也有很高的复发率。尽管治疗仅限于细胞减灭术和铂类化疗,但其他使用抗血管生成剂和聚(ADP-核糖)聚合酶抑制剂的疗法正在被测试。然而,这些治疗策略的效果不佳,因此需要新的潜在靶点和方法。本综述重点介绍了卵巢癌细胞中抗血管生成策略的最新证据,以及 Notch 和 β-catenin 蛋白所调控的机制。它还描述了使用血小板衍生生长因子(PDGFB)分子作为调节卵巢肿瘤血管生成的工具来实现“血管正常化”的概念,从而改善卵巢肿瘤的治疗。据报道,Notch 系统成分的改变和经典 Wnt/β-catenin 信号通路的改变,即我们感兴趣的另一个通路,与有助于卵巢癌发展的分子事件相关。因此,在本综述中,我们将卵巢肿瘤生物学的这些方面视为治疗这种疾病的潜在新治疗策略。

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