Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan.
Department of Obstetrics and Gynecology, Chia-Yi Chang Gung Memorial Hospital, Chia-Yi, Taiwan.
Taiwan J Obstet Gynecol. 2024 Jul;63(4):471-478. doi: 10.1016/j.tjog.2024.05.006.
Platinum-resistant ovarian cancer (PROC) refers to disease progression within 6 months after the completion of platinum-based chemotherapy. Historically, treatment options for PROC were limited with a poor prognosis and non-platinum single agent plus bevacizumab has been the mainstay of treatment. Fortunately, there have been notable advancements in recent years, leading to an advance in treatment paradigms for this challenging disease. Various combinations of chemotherapy, targeted agents such as poly (ADP-ribose) polymerase (PARP) inhibitors, and immunotherapy are being explored for an improved treatment outcome. Antibody-drug conjugates targeting folate receptor alpha, which deliver a cytotoxic payload directly to cancer cells, have emerged as a promising therapeutic approach for PROC. WEE1 inhibitors, such as adavosertib, function by inhibiting the WEE1 kinase activity, leading to premature entry of a cell into mitosis phase and thus increased DNA damage. It has been observed that cancer cells with TP53 mutations may be more sensitive to WEE1 inhibitors. Biomarker testing such as analysis of the expression level of folate receptor alpha or mutation in TP53 may be applicable for identifying patients who are more likely to respond to the specific therapy, enabling a more personalized treatment approach. This overview summarizes key clinical findings on the efficacy and safety of theses novel biomarker-driven therapeutic approaches.
铂耐药性卵巢癌（PROC）是指在铂类化疗完成后 6 个月内疾病进展。历史上，PROC 的治疗选择有限，预后较差，非铂类单药加贝伐珠单抗一直是治疗的主要方法。幸运的是，近年来取得了显著进展，为这一具有挑战性的疾病的治疗模式带来了进步。正在探索各种化疗药物联合、靶向药物（如聚（ADP-核糖）聚合酶（PARP）抑制剂）和免疫疗法，以改善治疗效果。针对叶酸受体α的抗体药物偶联物（ADC）已成为治疗 PROC 的一种有前途的治疗方法，因为它们可以将细胞毒性有效载荷直接递送到癌细胞中。WEE1 抑制剂（如adavosertib）通过抑制 WEE1 激酶活性起作用，导致细胞过早进入有丝分裂阶段，从而增加 DNA 损伤。已经观察到，具有 TP53 突变的癌细胞可能对 WEE1 抑制剂更敏感。生物标志物检测，如叶酸受体α的表达水平或 TP53 突变的分析，可能适用于识别更有可能对特定治疗产生反应的患者，从而实现更个性化的治疗方法。这篇综述总结了这些新型基于生物标志物的治疗方法的疗效和安全性的关键临床发现。
