I ran into a recently published and provocative article  by chance. Although this is not in the mainstream of [i]Menopause Live[/i] fields of interest, it certainly deals with an important aspect of adult women’s health – treatment of cancer. The main goal of chemo- and radiotherapy is eradication of cancer cells. However, we all know that this is just wishful thinking since total and permanent eradication cannot be achieved. Tumors eventually develop resistance because of multiple potential reasons such as localized hypoxia and poor vascularization, and phenotypic resistance to drug-induced toxicity through upregulation of DNA repair mechanisms and silencing of apoptotic pathways. The conventional therapeutic approach seems a ‘lost battle’ since resistant tumor cells will emerge eventually and the disease may recur despite a ‘successful’ treatment. Therefore, a major change in strategy should perhaps be considered.
Based on many previous studies in animals, and using a complicated mathematical model of tumor growth during and post chemotherapy, the authors of this study bring a new concept that says that we should not aim at eradication but at stabilization of the neoplastic tissue. The idea is to reduce the fitness of a tumor without causing too much cytotoxicity; this would lead to stabilization of the cancer cell population without producing strong selective forces for resistant phenotypes. In short, instead of a ‘must cure’ policy, using maximum tolerated doses, why not consider turning malignancies into a sort of chronic disease, perhaps a ‘live and let live’ approach. It seems crazy at first glance but, actually, why not try and see if this model really works?
Now, the main question is, of course, how to slow down the tumor growth and keep its volume steady. One of the authors’ suggestions is derived from the knowledge that solid tumor cells that are situated at the tumor center and experiencing hypoxia must rely on anaerobic glucose metabolism in order to survive. These are also the cells that may have a better chance to survive chemotherapy since the further a cell is from the surface of the malignant mass, the less its exposure to the destructive effect of treatment. 2-Deoxy-glucose, which inhibits normal glycolysis by competition, may be used in this context. However, simulations using the theoretical model showed that adding 2-deoxy-glucose after chemotherapy may yield better results than concomitant administration. In my eyes, new, unorthodox approaches to treatment of severe diseases may lead to breakthrough, innovative therapies pushing medicine beyond its current frontiers.
Department of Medicine T, Ichilov Hospital, Tel-Aviv, Israel
Silva AS, Gatenby RA. A theoretical quantitative model for evolution of cancer chemotherapy resistance. Biol Direct 2010;5:25. Published April 20, 2010. (The article can be downloaded freely from PubMed)