Department of Medical Biophysics, Institute of Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 141/143 Pomorska Street, 90-236 Lodz, Poland.
Int J Mol Sci. 2024 Nov 6;25(22):11927. doi: 10.3390/ijms252211927.
Epithelial ovarian cancer (EOC) is the most lethal gynecological malignancy worldwide. Due to its nonspecific symptoms and unreliable screening tools, EOC is not diagnosed at an early stage in most cases. Unfortunately, despite achieving initial remission after debulking surgery and platinum-based chemotherapy, most patients experience the recurrence of the disease. The limited therapy approaches have encouraged scientists to search for new detection and therapeutic strategies. In this review, we discuss the role of folate receptor alpha (FRα) in EOC development and its potential application as a biomarker and molecular target in designing new EOC screening and treatment methods. We summarize the mechanisms of the action of various therapeutic strategies based on FRα, including MABs (monoclonal antibodies), ADCs (antibody-drug conjugates), FDCs (folate-drug conjugates), SMDCs (small molecule-drug conjugates), vaccines, and CAR-T (chimeric antigen receptor T) cells, and present the most significant clinical trials of some FRα-based drugs. Furthermore, we discuss the pros and cons of different FR-based therapies, highlighting mirvetuximab soravtansine (MIRV) as the currently most promising EOC-targeting drug.
上皮性卵巢癌(EOC)是全球最致命的妇科恶性肿瘤。由于其症状不具特异性且缺乏可靠的筛查手段,大多数情况下 EOC 无法在早期被诊断出来。不幸的是,尽管在肿瘤细胞减灭术和铂类化疗后实现了初始缓解,但大多数患者仍会出现疾病复发。有限的治疗方法促使科学家们寻找新的检测和治疗策略。在这篇综述中,我们讨论了叶酸受体α(FRα)在 EOC 发展中的作用及其作为生物标志物和分子靶点在设计新的 EOC 筛查和治疗方法中的潜在应用。我们总结了基于 FRα 的各种治疗策略的作用机制,包括 MABs(单克隆抗体)、ADC(抗体药物偶联物)、FDC(叶酸药物偶联物)、SMDC(小分子药物偶联物)、疫苗和 CAR-T(嵌合抗原受体 T)细胞,并介绍了一些基于 FRα 的药物的最重要临床试验。此外,我们讨论了不同 FR 基疗法的优缺点,强调 mirvetuximab soravtansine(MIRV)是目前最有前途的 EOC 靶向药物。