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贝伐单抗在卵巢癌治疗中的应用:当前进展、临床挑战及新兴策略

Bevacizumab in ovarian cancer therapy: current advances, clinical challenges, and emerging strategies.

作者信息

Zhang Mingyue, Zhu Jun, Bao Yin, Ao Qiang, Mao Xiaoling, Qiu Zhengzhou, Zhang Yiming, Chen Yang, Zhu Hong, Gao Jun

机构信息

School of Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang, China.

Department of Gynecologic Oncology, Jiangxi Cancer Hospital and Institute, Jiangxi Clinical Research Center for Cancer, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, China.

出版信息

Front Bioeng Biotechnol. 2025 May 15;13:1589841. doi: 10.3389/fbioe.2025.1589841. eCollection 2025.

Abstract

Bevacizumab targets the vascular endothelial growth factor signaling pathway, inhibiting tumor angiogenesis and reshaping the tumor microenvironment, positioning it as a cornerstone in ovarian cancer management. Its mechanisms of action include blocking VEGF-A-induced endothelial cell proliferation, promoting vascular normalization, alleviating hypoxic conditions, and reversing immunosuppression. Key phase III clinical trials, including GOG-0218, AURELIA, and PAOLA-1, have demonstrated that Bevacizumab significantly extends progression-free survival in the maintenance treatment of newly diagnosed advanced ovarian cancer, platinum-sensitive or resistant recurrent disease, and HRD-positive patients, with a median PFS of up to 37.2 months. However, its impact on overall survival remains limited, and challenges such as drug resistance, treatment-related toxicities, and high costs persist. Future advancements will hinge on multidisciplinary innovation, including dual-targeting approaches such as VEGF/Ang-2 bispecific antibodies, combination immunotherapies, intelligent nanodrug delivery systems, and AI-driven dynamic biomarker stratification. The use of biosimilars and adaptive platform trials offers promise in reducing costs and improving accessibility. These technological innovations mark a shift in ovarian cancer treatment from traditional chemotherapy to precision medicine, presenting new opportunities to improve long-term patient survival.

摘要

贝伐单抗靶向血管内皮生长因子信号通路,抑制肿瘤血管生成并重塑肿瘤微环境,使其成为卵巢癌治疗的基石。其作用机制包括阻断VEGF - A诱导的内皮细胞增殖、促进血管正常化、缓解缺氧状况以及逆转免疫抑制。关键的III期临床试验,包括GOG - 0218、AURELIA和PAOLA - 1,已证明贝伐单抗在新诊断的晚期卵巢癌、铂敏感或耐药复发性疾病以及HRD阳性患者的维持治疗中显著延长无进展生存期,中位无进展生存期长达37.2个月。然而,其对总生存期的影响仍然有限,耐药、治疗相关毒性和高成本等挑战依然存在。未来的进展将取决于多学科创新,包括VEGF/Ang - 2双特异性抗体等双靶点方法、联合免疫疗法、智能纳米药物递送系统以及人工智能驱动的动态生物标志物分层。生物类似药的使用和适应性平台试验有望降低成本并提高可及性。这些技术创新标志着卵巢癌治疗从传统化疗向精准医学的转变,为提高患者长期生存率带来了新机遇。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2bbf/12138263/a64d3b8618f9/fbioe-13-1589841-g001.jpg

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