Zhang Hairong, Gong Cuiping, Lv Xin
Department of Obstetrics and Gynecology, Shandong Provincial Third Hospital, Shandong University, Ji'nan, China.
Front Pharmacol. 2025 Jul 17;16:1604998. doi: 10.3389/fphar.2025.1604998. eCollection 2025.
Ovarian cancer (OC) remains one of the most lethal malignancies affecting women, largely due to its asymptomatic onset and the consequent challenges in early detection and diagnosis. This often results in delayed treatment and poor clinical outcomes. Among gynecological cancers, OC exhibits the highest mortality rate. While current therapeutic approaches such as surgery and chemotherapy provide initial clinical benefit, they are frequently undermined by high rates of recurrence and metastasis. Moreover, the pronounced heterogeneity of OC further complicates treatment, highlighting the urgent need for novel therapeutic targets and more effective strategies. The forkhead box (FOX) family of transcription factors comprises a large group of proteins involved in regulating gene expression across various biological processes. Dysregulation of FOX family members has been implicated in aberrant cellular behaviors, including uncontrolled proliferation, resistance to apoptosis, enhanced invasiveness, metastatic potential, and the development of drug resistance. Importantly, the functional roles of individual FOX proteins vary significantly depending on the tumor context, reflecting the functional diversity of this family. This review aims to provide a comprehensive overview of the emerging roles of FOX family members in the pathogenesis and progression of OC, as well as recent advances in FOX-targeted therapeutic strategies.
卵巢癌（OC）仍然是影响女性的最致命恶性肿瘤之一，这主要归因于其无症状发病以及早期检测和诊断方面随之而来的挑战。这常常导致治疗延迟和临床结果不佳。在妇科癌症中，OC的死亡率最高。虽然目前的治疗方法，如手术和化疗能带来初步的临床益处，但它们常常因高复发率和转移率而受到影响。此外，OC显著的异质性使治疗更加复杂，凸显了对新型治疗靶点和更有效策略的迫切需求。叉头框（FOX）转录因子家族由一大类参与调控各种生物学过程中基因表达的蛋白质组成。FOX家族成员的失调与异常的细胞行为有关，包括不受控制的增殖、对凋亡的抵抗、侵袭性增强、转移潜能以及耐药性的发展。重要的是，单个FOX蛋白的功能作用因肿瘤背景而异，这反映了该家族的功能多样性。本综述旨在全面概述FOX家族成员在OC发病机制和进展中的新作用，以及FOX靶向治疗策略的最新进展。
