Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Fred & Pamela Buffett Cancer Center, University of Nebraska Medical Center, Omaha, NE 68198-6805, USA.
Int J Mol Sci. 2024 May 7;25(10):5067. doi: 10.3390/ijms25105067.
Ovarian cancer is the deadliest gynecologic malignancy. The majority of patients diagnosed with advanced ovarian cancer will relapse, at which point additional therapies can be administered but, for the most part, these are not curative. As such, a need exists for the development of novel therapeutic options for ovarian cancer patients. Research in the field of targeted protein degradation (TPD) through the use of proteolysis-targeting chimeras (PROTACs) has significantly increased in recent years. The ability of PROTACs to target proteins of interest (POI) for degradation, overcoming limitations such as the incomplete inhibition of POI function and the development of resistance seen with other inhibitors, is of particular interest in cancer research, including ovarian cancer research. This review provides a synopsis of PROTACs tested in ovarian cancer models and highlights PROTACs characterized in other types of cancers with potential high utility in ovarian cancer. Finally, we discuss methods that will help to enable the selective delivery of PROTACs to ovarian cancer and improve the pharmacodynamic properties of these agents.
卵巢癌是致死率最高的妇科恶性肿瘤。大多数被诊断为晚期卵巢癌的患者会复发，此时可以给予其他治疗方法，但这些方法在大多数情况下并不能治愈。因此，需要为卵巢癌患者开发新的治疗选择。近年来，通过使用蛋白水解靶向嵌合体（PROTAC）进行靶向蛋白降解（TPD）的研究显著增加。PROTAC 能够靶向感兴趣的蛋白（POI）进行降解，克服了其他抑制剂存在的不完全抑制 POI 功能和耐药性发展等限制，在癌症研究中，包括卵巢癌研究中具有特别的意义。本综述概述了在卵巢癌模型中测试的 PROTAC，并强调了在其他类型癌症中具有潜在高应用价值的 PROTAC。最后，我们讨论了有助于将 PROTAC 选择性递送至卵巢癌并改善这些药物的药效学特性的方法。
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