New light on chemotherapy toxicity and its prevention

Most patients with cancer receive chemotherapy. Unfortunately, chemotherapy is associated with a number of potentially life-threatening side effects. There is a need to ameliorate chemotoxicity to improve therapeutic outcomes and quality of life. Chemotoxicity arises from systemic DNA damage and inflammation in healthy cells due to chemotherapy drugs. Traditionally, these processes are believed to be caused by the direct death of normal cells by chemotherapeutic drugs. However, new research has challenged this dogma by suggesting that chemotoxicity is a secondary effect associated with the release of cell-free chromatin particles (cfChPs) from cells subjected to drug-induced death. Released cfChPs can freely enter into bystander healthy cells to inflict double-strand (dsDNA) breaks and activate inflammatory and apoptotic pathways. The drug-induced cell death and cfChPs release have cascading effects that exaggerate and prolong chemotoxicity. Furthermore, evidence has emerged from laboratory and preclinical studies, and two phase II clinical trials, indicating that chemotoxicity can be minimised by deactivating cfChPs. Three cfChPs-deactivating agents have been identified, of which the nutraceutical combination resveratrol and copper (R-Cu)-easily administered orally and with little toxicity-is the agent of choice for human therapeutic use. This article aims to provide practising medical oncologists with a perspective on this emerging research on chemotoxicity and its prevention and its potential implications for the future. Well-designed randomised clinical trials will be necessary to establish the true clinical value of these findings in day-to-day practice.