Cancer Program, Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC 3800, Australia.
Neil Beauglehall Department of Medical Oncology Research, Cabrini Health, Malvern, VIC 3144, Australia.
Biomolecules. 2024 May 15;14(5):585. doi: 10.3390/biom14050585.
Epithelial ovarian cancer (EOC) is one of the most aggressive forms of gynaecological malignancies. Survival rates for women diagnosed with OC remain poor as most patients are diagnosed with advanced disease. Debulking surgery and platinum-based therapies are the current mainstay for OC treatment. However, and despite achieving initial remission, a significant portion of patients will relapse because of innate and acquired resistance, at which point the disease is considered incurable. In view of this, novel detection strategies and therapeutic approaches are needed to improve outcomes and survival of OC patients. In this review, we summarize our current knowledge of the genetic landscape and molecular pathways underpinning OC and its many subtypes. By examining therapeutic strategies explored in preclinical and clinical settings, we highlight the importance of decoding how single and convergent genetic alterations co-exist and drive OC progression and resistance to current treatments. We also propose that core signalling pathways such as the PI3K and MAPK pathways play critical roles in the origin of diverse OC subtypes and can become new targets in combination with known DNA damage repair pathways for the development of tailored and more effective anti-cancer treatments.
上皮性卵巢癌（EOC）是妇科恶性肿瘤中最具侵袭性的一种。由于大多数患者在疾病晚期才被诊断出来，因此被诊断为 OC 的女性的存活率仍然很低。肿瘤细胞减灭术和铂类药物治疗是目前 OC 治疗的主要方法。然而，尽管最初达到缓解，但由于先天和获得性耐药，很大一部分患者会复发，此时疾病被认为是无法治愈的。鉴于此，需要新的检测策略和治疗方法来改善 OC 患者的预后和生存。在这篇综述中，我们总结了我们目前对 OC 及其多种亚型的遗传景观和分子途径的认识。通过检查临床前和临床环境中探索的治疗策略，我们强调了解单个和收敛性遗传改变如何共存并推动 OC 进展以及对当前治疗方法的耐药性的重要性。我们还提出，核心信号通路，如 PI3K 和 MAPK 通路，在上皮性卵巢癌不同亚型的起源中起着关键作用，并可与已知的 DNA 损伤修复途径相结合，成为开发针对特定人群的、更有效的抗癌治疗方法的新靶点。
