血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKIs）在癌症治疗中的高血压毒性：发生率、机制与管理策略
Hypertension toxicity of VEGFR-TKIs in cancer treatment: incidence, mechanisms, and management strategies
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影响因子:6.9
分区:医学2区 / 毒理学1区
发表日期:2025 Jan
作者:
Yan-Xi Du, Xu Li, Si-Wen Ji, Na Niu
DOI:
10.1007/s00204-024-03874-4
摘要
血管内皮生长因子受体酪氨酸激酶抑制剂（VEGFR-TKIs）是一类靶向抗癌药物，包括帕唑帕尼、舒尼替尼、阿昔替尼等。目前，VEGFR-TKIs广泛用于多种肿瘤的临床治疗中，能延长患者生存甚至治愈肿瘤。然而，使用VEGFR-TKIs常伴随心血管不良事件的发生，其中高血压最为常见。高血压及其并发症会严重影响患者预后，可能危及生命，甚至在重症情况下导致治疗中断或停止。本文综述了VEGFR-TKIs引起高血压的发生率、毒性机制、管理策略及未来研究方向。此外，VEGFR-TKIs引发的高血压可能与盐敏感性有关，其可能机制包括血管扩张剂失衡、毛细血管密度下降、肾损伤、氧化应激引起的内皮功能障碍、淋巴血管密度下降以及“非目标作用”。全面了解VEGFR-TKIs癌症治疗中高血压的毒性，有助于优化临床实践，改善患者预后。
Abstract
Vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs) are a class of targeted anticancer agents that include pazopanib, sunitinib, axitinib, and others. Currently, VEGFR-TKIs are widely used in the clinical treatment of various tumors, which can prolong patients' survival and even cure tumors. However, the use of VEGFR-TKIs is frequently associated with the occurrence of cardiovascular adverse events, with hypertension being the most prevalent. Hypertension and its complications can significantly impact the prognosis of patients, potentially jeopardizing their lives and resulting in the reduction or even cessation of treatment in severe cases. This review addresses the incidence of hypertension due to VEGFR-TKIs, mechanisms of toxicity, management strategies, and future research directions. In addition, hypertension due to VEGFR-TKIs may be associated with salt sensitivity, and possible mechanisms of hypertensive side effects are vasodilator imbalance, decreased capillary density, renal injury, impaired endothelial function due to oxidative stress, decreased lymphatic vascular density, and "off-target effect". A comprehensive understanding of hypertension toxicity due to cancer treatment with VEGFR-TKIs, can enhance clinical practice, thereby improving the prognostic outcomes of VEGFR-TKIs in oncology patients.