Department of Gynecology and Obstetrics, Yas Hospital, Tehran University of Medical Sciences, Tehran, Iran.
M.D, Arak University of Medical Sciences, Arak, Iran.
Pathol Res Pract. 2024 Nov;263:155611. doi: 10.1016/j.prp.2024.155611. Epub 2024 Sep 25.
Cancer continues to threaten human health regardless of novel therapeutic options. Over the last two decades, targeted therapy has emerged as a significant advancement in treating malignancies, surpassing standard chemoradiotherapy and surgical procedures. Gynecological malignancies, including cervical, endometrial, and ovarian carcinoma, have a bad prognosis in advanced or metastatic stages and are difficult to treat. The advancements in understanding the molecular pathways behind cancer development offer valuable insights into promising targeted medicines, and researchers have always searched for a superior and safe technique to target cancer-related oncoproteins because of the limited therapeutic benefit, drug resistance, and off-target effects of current targeted treatments. Recently, proteolysis-targeting chimeras (PROTACs) have been developed to selectively degrade proteins using the natural ubiquitin-proteasome system (UPS). These approaches have garnered significant attention in the field of cancer research. The rapid progress in PROTACs has also eased the targeting of various oncoproteins in gynecological cancer. Therefore, this review aims to elucidate the mechanism and research advancements of PROTACs and provide a comprehensive overview of their use in gynecological tumors.
癌症仍然威胁着人类健康,无论新的治疗选择如何。在过去的二十年中,靶向治疗已成为治疗恶性肿瘤的重大进展,超越了标准的放化疗和手术。妇科恶性肿瘤,包括宫颈癌、子宫内膜癌和卵巢癌,在晚期或转移性阶段预后不良,难以治疗。对癌症发展背后的分子途径的理解的进步为有前途的靶向药物提供了有价值的见解,由于当前靶向治疗的治疗益处有限、耐药性和脱靶效应,研究人员一直在寻找一种更优越和安全的技术来靶向与癌症相关的癌蛋白。最近,已经开发了蛋白水解靶向嵌合体(PROTACs),以利用天然的泛素-蛋白酶体系统(UPS)选择性降解蛋白质。这些方法在癌症研究领域引起了广泛关注。PROTACs 的快速发展也使得针对妇科癌症中的各种癌蛋白变得更加容易。因此,本综述旨在阐明 PROTACs 的作用机制和研究进展,并全面概述其在妇科肿瘤中的应用。