Chemotherapy-induced oxidative stress in nontargeted normal tissues

Chemotherapy has played a critical role in increasing the number of cancer survivors. The success rate of chemotherapy is contributed, in part, by the development of novel agents and more aggressive treatment strategies. However, the effect that chemotherapeutic drugs have on normal tissue can create serious dose-limiting and quality-of-life issues. The majority of the known side effects of chemotherapy are related to proliferating tissues, which can be renewed and replaced. However, the effect of chemotherapeutic agents on tissues with limited renewal capability, such as cardiac and neuronal tissues, is of serious concern. The anticancer effect of the current FDA approved chemotherapeutic agents can be classified into multiple groups based on their predicted mechanisms of toxicity, and generation of reactive oxygen species (ROS) in normal tissue is implicated in a large number of these agents. However, how tissue pathology is induced by ROS-generating chemotherapeutic agents is unclear. Furthermore, the underlying mechanisms by which these agents affect a selected target tissue are relatively unexplored. This review briefly discusses these unexplored areas focusing on cardiac and neuronal tissues. The goal is to provide the basis for future development of anticancer drugs with reduced normal tissue injury to improve the quality of life for the ever-increasing number of cancer survivors.