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09 January 2013Title:Oxidants, antioxidants and the current incurability of high Myc-driven cancersAuthors:Dr James D. Watson, Cold Spring Harbour LaboratoryJournal:Open Biology
Although mortality from many cancers has been steadily falling, particularly those of the blood (i.e., leukemias), epithelial cancers (carcinomas) and effectively all mesenchymal cancers (sarcomas) remain largely incurable. In Open Biology today, Nobel laureate James D. Watson, Ph.D., presents a novel hypothesis regarding the role of oxidants and antioxidants in cancers that are currently incurable, notably in late-stage metastatic cancers. Watson claims that antioxidants in late-stage cancers can promote cancer progression, a theory he counts “among my most important work since the double helix”.
Dr James Watson. Photo Credit: Jacob Forsell, Hagersten, Sweden
At the heart of his thesis are the group of molecules that scientists call reactive oxygen species. ROS play a role in apoptosis, which allows dysfunctional cells which pose a threat to the survival or organisms to kill themselves. Watson calls ROS “a positive force for life”.
However, ROS are also able to irreversibly damage key proteins and nucleic acid molecules [e.g., DNA and RNA]. Thus under normal circumstances, when they’re not needed to curb dysfunctional cells, ROS are constantly being neutralized by anti-oxidative proteins. In order to aid this neutralization, we are often urged to eat foods rich in antioxidants such as blueberries. Watson claims that in late-stage cancer, as ROS are needed for apoptosis, suppressing them may promote the progression of threatening cells and hence cancer. He writes “blueberries best be eaten because they taste good, not because their consumption will lead to less cancer.”
Watson also proposes that the cell-killing ability of currently used anti-cancer therapies – notably, toxic chemotherapeutic agents such as Taxol as well as radiation treatment – is mainly due to the action of ROS to induce apoptosis, or programmed cell death. If true, this would explain “why cancers that become resistant to chemotherapeutic control become equally resistant to ionizing radiotherapy.” The common feature would be their common dependence upon a ROS-mediated cell-killing mechanism.
Watson again applies his theory to suggest that cancer cells largely driven by mutant proteins such as RAS and MYC are often hardest to get to respond to treatment because of their high levels of ROS-destroying antioxidants.
Given the current methods of treatment and pace of research, Watson concludes that “Unless we can find ways of reducing antioxidant levels, late-stage cancer 10 years from now will be as incurable as it is today.”
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