甲磺酸阿帕替尼治疗乳腺癌的研究进展： 从机制到临床实践

Research Progress on Apatinib in the Treatment of Breast Cancer: From Mechanism to Clinical Practice

摘要: 本文系统综述了抗血管生成药物阿帕替尼在乳腺癌治疗中的研究进展与应用前景。乳腺癌是全球高发恶性肿瘤，现有治疗手段如内分泌治疗、化疗、靶向治疗及免疫治疗仍存在局限性，包括特定亚型疗效不足、毒副作用显著、耐药性以及疗效异质性等问题。阿帕替尼作为高选择性VEGFR-2抑制剂，通过阻断PI3K/AKT、NF-κB等下游信号通路，抑制肿瘤血管生成，并可调节免疫微环境，增强抗肿瘤免疫应答。临床前研究表明，阿帕替尼能有效抑制乳腺癌细胞增殖、迁移、侵袭及干细胞活性。临床研究显示，阿帕替尼单药或联合化疗、免疫治疗及放疗在晚期乳腺癌(包括三阴性乳腺癌和HER2阳性型)中表现出一定的疾病控制作用，有助于延长患者无进展生存期与总生存期。其常见不良反应如高血压、手足综合征、蛋白尿等可通过剂量调整与对症支持进行管理。未来研究需进一步探索阿帕替尼与不同疗法的协同作用、个体化给药策略、疗效预测生物标志物，并通过多学科诊疗模式应对耐药与毒性管理问题，以提升其在乳腺癌治疗中的精准性与临床效益。

Abstract: This article provides a systematic review of the research progress and application prospects of the anti-angiogenic drug apatinib in the treatment of breast cancer. Breast cancer is a prevalent malignant tumor worldwide, and current treatment modalities—including endocrine therapy, chemotherapy, targeted therapy, and immunotherapy—still face limitations such as insufficient efficacy in specific subtypes, significant toxic side effects, drug resistance, and heterogeneous treatment responses. As a highly selective VEGFR-2 inhibitor, apatinib suppresses tumor angiogenesis by blocking downstream signaling pathways such as PI3K/AKT and NF-κB, while also modulating the immune microenvironment and enhancing anti-tumor immune responses. Preclinical studies have demonstrated that apatinib can effectively inhibit the proliferation, migration, invasion, and stem cell activity of breast cancer cells. Clinical research indicates that apatinib, either as monotherapy or in combination with chemotherapy, immunotherapy, and radiotherapy, exhibits certain disease-controlling effects in advanced breast cancer (including triple-negative breast cancer and HER2-positive subtypes), contributing to prolonged progression-free survival and overall survival in patients. Common adverse reactions such as hypertension, hand-foot syndrome, and proteinuria can be managed through dose adjustment and supportive care. Future studies should further explore the synergistic effects of apatinib with different therapies, individualized dosing strategies, biomarkers for predicting therapeutic efficacy, and address issues of drug resistance and toxicity management through multidisciplinary approaches, so as to enhance the precision and clinical benefits of apatinib in breast cancer treatment.