The beginning of a new year is a time for reflection. There have been two news items which have struck me in regard to epigenetics and cancer research, recently.
Dr. James Watson, Nobel Prize winner, and co-discoverer of the double helix structure of DNA, has published a controversial, open access paper in the journal Open Biology. Cancer research has not produced cures, but merely temporary life extentions for those facing metastatic cancers. The sequencing of the human genome and identification of individual cancer cell mutation drivers of disease, have not produced cures. Dr. Watson points out that once cancer turns metastatic, resistance to gene-targeted drugs is rampant. In the metastatic process, DNA sequence mutations often don’t change. Rather their expression changes. Multiple molecular pathways are enabling drug resistance to tumors in new surrounding environments. Dr. Watson recommends research focuses on the protein Myc, (supported by Bromodomain 4) as a common driver of resistance pathways. Dr. Watson also was quoted saying that “The time has come to seriously ask whether antioxidant use much more likely causes than prevents cancer.” The basis of this idea is that chemotherapy and radiation treatments rely on oxidized free radicals to kill cancer cells. You can read the full paper here.
The second paper that turned my head over the holidays was Kreso A. et al. Variable Clonal Repopulation Dynamics Influence Chemotherapy Response in Colorectal Cancer (2012) Science This work was surprising because it demonstrated how tumors with the same genomes were behaving quite differently based on their environments. Again, functional drug resistance is based more on epigenetics than genetics.
Undoubtedly, scientists will reflect on these ideas and become even more resolved to apply epigenetics and cell signaling research in the “war on cancer”. It is critical that scientists collaborate to incorporate data from of all molecular systems to propel cancer research forward. The complexity of this disease will likely require equally complex combinational treatments to attain a real cure.
Watson J (2013). Oxidants, antioxidants and the current incurability of metastatic cancers. Open biology, 3 (1) PMID: 23303309