Chemotherapeutic Agents in Cancer Treatment and Tryptophan Metabolism

KESİKLİ S. A., Guler N.



Cancer is the uncontrolled division and accumulation of cells in any part of the body. Surgery, radiotherapy, and systemic therapies are the main treatment strategies against cancers. However, systemic chemotherapy has various side effects, including nausea, vomiting, myelosuppression, cardiotoxicity (with anthra-cyclines), neurotoxicity (with mitotic spindle poisons), and nephrotoxicity (with platinum analogs). Although surgery can be curative in some cases, the main purposes of cancer treatments, especially in metastatic cancer patients, are the palliation of symptoms and increasing survival with better quality of life. Increasing the effi cacy and decreasing the toxicity of chemotherapeutic agents are currently the main challenges in cancer treatment, for which substantial effort has been given for years. Melatonin is a hormone produced in the pineal gland from the essential amino acid tryptophan. It is one of the strongest antioxidants identifi ed, with additional chemopreventive, oncostatic, and tumor inhibitory effects in a variety of in vitro and in vivo experimental cancer models. In addition to melatonin synthesis, tryptophan is involved in numerous metabolic activities in the human body, including the bio-synthesis of serotonin, kynurenine, and nicotinamide, thereby regulating circadian rhythm, learning, memory, sleep, behavior, mood, appetite, aging, growth, reproduction, immune system, and cancer development. Therefore, tryptophan-related metabolic pathways and catabolites have gained considerable attention, especially in improving cancer treatment and predicting disease activity as well as patient survival. This chapter mainly focuses on the relationship between tryptophan metabolism and chemotherapy; the prognostic value of tryptophan catabolites as cancer biomarkers, tryptophan metabolism, and cancer-related fatigue; the association between melatonin and cancer therapy as well as chemotherapy side effects; and the significance of chronochemotherapy after an initial brief introduction about chemotherapeutic agents.