Division of Nephrology, Department of Internal Medicine, University of Texas Health Science Center-McGovern Medical School, Houston, Texas.
Section of Nephrology, Department of Internal Medicine, Yale School of Medicine, New Haven, CT.
Kidney360. 2024 Nov 1;5(11):1750-1762. doi: 10.34067/KID.0000000566. Epub 2024 Aug 26.
Molecular targeted therapy has revolutionized cancer treatment by significantly improving patient survival compared with standard conventional chemotherapies. The use of these drugs targets specific molecules or targets, which block growth and spread of cancer cells. Many of these therapies have been approved for use with remarkable success in breast, blood, colorectal, lung, and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drugs effectively with high specificity while being less toxic. Although known as "targeted," many of these agents lack specificity and selectivity, and they tend to inhibit multiple targets, including those in the kidneys. The side effects usually arise because of dysregulation of targets of the inhibited molecule in normal tissue. The off-target effects are caused by drug binding to unintended targets. The on-target effects are associated with inhibition toward the pathway reflecting inappropriate inhibition or activation of the intended drug target. Early detection and correct management of kidney toxicities is crucial to preserve kidney functions. The knowledge of these toxicities helps guide optimal and continued utilization of these potent therapies. This review summarizes the different types of molecular targeted therapies used in the treatment of cancer and the incidence, severity, and pattern of nephrotoxicity caused by them, with their plausible mechanism and proposed treatment recommendations.
分子靶向治疗通过与标准常规化疗相比显著提高患者生存率,从而彻底改变了癌症治疗。这些药物的使用针对特定的分子或靶点,从而阻断癌细胞的生长和扩散。许多这些疗法已被批准用于乳腺癌、血液癌、结直肠癌、肺癌和卵巢癌,取得了显著的成功。与常规化疗相比,其优势在于能够以高特异性有效递送药物,同时毒性更小。尽管被称为“靶向”,但这些药物中的许多缺乏特异性和选择性,它们往往会抑制多个靶点,包括肾脏中的靶点。副作用通常是由于抑制分子在正常组织中的靶标失调引起的。脱靶效应是由药物与非预期靶标结合引起的。靶标效应与抑制途径相关,反映了对药物靶标的不适当抑制或激活。早期发现和正确管理肾毒性对于保护肾功能至关重要。了解这些毒性有助于指导这些有效治疗方法的最佳和持续利用。本文综述了用于癌症治疗的不同类型的分子靶向治疗以及它们引起的肾毒性的发生率、严重程度和模式,以及其可能的机制和提出的治疗建议。