An overview of chemotoxicity and radiation toxicity in cancer therapy.

While immunotherapy and targeted therapies represent major advances against different types of malignancies, the mainstay of cancer therapy continues to be radiation and surgery for localized disease, and chemotherapy for systemic disease, with the preponderance of chemotherapeutic agents (such as anthracyclines, alkylating agents, and antimetabolites) having been developed decades ago. Combination chemotherapy regimens have changed the natural history of once deadly diseases such as breast and prostate cancer and led to curative regimens in advanced hematological malignancies and testicular cancer. However, while oncologists maintain their focus on disease suppression, and where feasible, disease eradication, obstacles to achieving cure remain, such as tumor dormancy and ultimately disease recurrence, as well as both intrinsic and acquired resistance. In this review, complications of current cancer therapies toward major organs (heart, lung, kidney, gastro-intestinal, neuromuscular, brain, and skin) are emphasized, and efforts to mitigate these complications are described. This is particularly relevant for patients treated with curative intent, where adherence to treatment plan, and avoidance of interruptions in treatment schedule are essential for optimal outcome. Consequently, these patients are treated with an "aggressive" approach, with high tolerance for side effects. However, a deeper understanding of normal tissue toxicity resulting from the different cancer therapies remains an area of unmet medical need that will ultimately lead to improved therapeutic index for current and future therapies, planning for treatment adverse effects, and ultimately improvement in patient satisfaction, compliance and outcome.