AKI Associated with Anti-cancer Therapies: Small Molecules and Targeted Therapies.

Abstract

Molecular targeted therapy has revolutionized cancer treatment by significantly improving the patient survival compared to 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, leukemia colorectal, lung and ovarian cancers. The advantage over conventional chemotherapy is its ability to deliver drug 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 towards 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 treatment of cancer, the incidence, severity and pattern of nephrotoxicity caused by them, with their plausible mechanism and proposed treatment recommendations.