Franczyk Beata, Rysz Jacek, Ławiński Janusz, Ciałkowska-Rysz Aleksandra, Gluba-Brzózka Anna
Department of Nephrology, Hypertension and Family Medicine, Medical University of Lodz, 113 Żeromskiego Street, 90-549 Lodz, Poland.
Department of Urology, Institute of Medical Sciences, Medical College of Rzeszow University, 35-055 Rzeszow, Poland.
Biomedicines. 2023 Jan 11;11(1):181. doi: 10.3390/biomedicines11010181.
Renal cell carcinoma (RCC) is one of the most frequent malignant neoplasms of the kidney. The therapeutic options available for the treatment of advanced or metastatic RCC include vascular endothelial growth factor receptor (VEGFR)-targeted molecules, for example, tyrosine kinase inhibitors (TKI). Various VEGFR-TKIs proved to be effective in the treatment of patients with solid tumours. The combination of two drugs may prove most beneficial in the treatment of metastatic RCC; however, it also enhances the risk of toxicity compared to monotherapy. Specific VEGFR-TKIs (e.g., sunitinib, sorafenib or pazopanib) may increase the rate of cardiotoxicity in metastatic settings. VEGF inhibitors modulate multiple signalling pathways; thus, the identification of the mechanism underlying cardiotoxicity appears challenging. VEGF signalling is vital for the maintenance of cardiomyocyte homeostasis and cardiac function; therefore, its inhibition can be responsible for the reported adverse effects. Disturbed growth factor signalling pathways may be associated with endothelial dysfunction, impaired revascularization, the development of dilated cardiomyopathy, cardiac hypertrophies and altered peripheral vascular load. Patients at high cardiovascular risk at baseline could benefit from clinical follow-up in the first 2-4 weeks after the introduction of targeted molecular therapy; however, there is no consensus concerning the surveillance strategy.
肾细胞癌（RCC）是肾脏最常见的恶性肿瘤之一。用于治疗晚期或转移性RCC的治疗选择包括血管内皮生长因子受体（VEGFR）靶向分子，例如酪氨酸激酶抑制剂（TKI）。各种VEGFR-TKI已被证明对实体瘤患者的治疗有效。两种药物联合使用可能对转移性RCC的治疗最为有益；然而，与单药治疗相比，它也增加了毒性风险。特定的VEGFR-TKI（如舒尼替尼、索拉非尼或帕唑帕尼）在转移性情况下可能会增加心脏毒性发生率。VEGF抑制剂可调节多种信号通路；因此，确定心脏毒性的潜在机制似乎具有挑战性。VEGF信号对于维持心肌细胞稳态和心脏功能至关重要；因此，其抑制可能是所报道不良反应的原因。生长因子信号通路紊乱可能与内皮功能障碍、血管再生受损、扩张型心肌病的发展、心脏肥大以及外周血管负荷改变有关。基线时心血管风险高的患者可能会从引入靶向分子治疗后的头2至4周的临床随访中受益；然而，关于监测策略尚无共识。
