In a new paper Nobelist James Watson sets forth a hypothesis regarding the role of oxidants and antioxidants in late-stage cancers
Cold Spring Harbor, NY — 鈥淎lthough mortality from many cancers has been steadily falling, particularly those of the blood [i.e., leukemias], the more important statistic may be that so many epithelial cancers (carcinomas) and effectively all mesenchymal cancers (sarcomas) remain largely incurable.鈥�
With these words as preface, Nobel laureate James D. Watson, Ph.D., in a newly published paper that he regards 鈥渁mong my most important work since the double helix,鈥� sets forth a novel hypothesis regarding the role of oxidants and antioxidants in cancers that are currently incurable, notably in late-stage metastatic cancers.
At the heart of his thesis are the group of molecules that scientists call reactive oxygen species, or ROS. Noting their fundamental two-sidedness, Watson calls ROS 鈥渁 positive force for life鈥� because of their role in apoptosis—an internal program that highly stressed cells use to commit suicide. It鈥檚 one of the key mechanisms that have arisen through eons of evolution to weed out biological dysfunction that poses a threat to the survival of organisms.聽On the other hand, ROS are also well understood—indeed are notorious—鈥渇or their ability to irreversibly damage key proteins and nucleic acid molecules [e.g., DNA and RNA].鈥�
When they鈥檙e not needed to curb wayward or out-of-control cells, which is to say under normal circumstances, ROS are constantly being neutralized by anti-oxidative proteins.聽We are often urged to eat foods rich in antioxidants such as blueberries; but, if Watson is correct about the role of ROS and antioxidants in late-stage cancer, as he writes in his new paper, 鈥渂lueberries best be eaten because they taste good, not because their consumption will lead to less cancer.鈥�
Understanding why this might be so—why antioxidants can in late-stage cancers actually promote cancer progression—is central to Watson鈥檚 paper, which appears online January 9 in Open Biology, a journal of Great Britain鈥檚 Royal Society.
He 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 鈥渨hy cancers that become resistant to chemotherapeutic control become equally resistant to ionizing radiotherapy.鈥� The common feature would be their common dependence upon a ROS-mediated cell-killing mechanism.
Watson, who is Chancellor Emeritus of 黑料吃瓜资源, then takes up the case of cancer cells largely driven by mutant proteins such as RAS and MYC.聽These, he notes, are often hardest to get to respond to treatment.聽He suggests this could be due to their high levels of ROS-destroying antioxidants. He cites recent research showing up-regulation of a gene transcription factor called Nrf2 when cells proliferate as well as when oncogenes such as RAS, MYC and RAF are active. Nrf2 controls the synthesis of antioxidants, and 鈥渢his makes sense because we want antioxidants present when DNA functions to make more of itself,鈥� Watson writes.
In general, the Nobel laureate wants those reading his new paper to consider a proposition he considers grossly underexplored: 鈥淯nless we can find ways of reducing antioxidant levels, late-stage cancer 10 years from now will be as incurable as it is today.鈥�
Written by: Peter Tarr, Senior Science Writer | [email protected] | 516-367-8455