Antioxidants and cancer therapy: furthering the debate.

The consideration of whether to use antioxidants concomitantly with chemotherapy and radiation therapy has evolved into a heated debate. This special theme issue brings together several contributors to this debate, whose perspectives enlarge our views of the questions at hand, pointing out several very relevant ideas. First, the early hypotheses of the role of antioxidants in carcinogenesis gave a simplified and often inaccurate picture of the physiological effects of specific antioxidants. Antioxidants can have protective effects that have nothing to do with oxidation; on the other hand, they can under some circumstances develop prooxidant properties and promote carcinogenesis. During treatment, however, their role is far from clear and may be either quite positive or potentially negative. A number of clinical studies have already demonstrated beneficial effects of antioxidants in ameliorating side effects of chemotherapy. More theoretical work on the chemistry of antioxidants and chemotherapy drugs suggests that antioxidants might improve therapeutic efficacy of antineoplastics by counteracting aldehydes that impede the passage of cells through the cell cycle. However, detailed clinical study also makes it clear that we are only at the very beginning of understanding the dynamics of antioxidants and oxidant damage in the body during conventional treatment. Nevertheless, research is under way on radioprotective and chemoprotective substances, some of them rooted in traditional medicine and others in our understanding of dietary antioxidants, that may eventually lead to antioxidant-based supplements that support tolerability and efficacy of treatment, without protecting tumors through interference from antineoplastic treatment.