A report of the James Watson lecture at Yale University.

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In March 2012, Nobel Prize winner James Watson gave a seminar at Yale University entitled "Driven by Ideas." In his lecture, Watson discussed his personal vision for the future of science, specifically addressing how the scientific community should approach developing anticancer agents. He discussed the use of glycolytic inhibitors as anticancer agents due to the Warburg effect, as well as the benefits of metformin and anti-inflammatory drugs to help prevent cancer. He also compared drugs that target cell proliferation instead of targeting cell growth. Additionally, Watsoncommented on the mechanisms for how research should be conducted in the laboratory.

2013 Jan 8;3(1):120144. doi: 10.1098/rsob.120144.

Oxidants, antioxidants and the current incurability of metastatic cancers.

Watson J1.

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The vast majority of all agents used to directly kill cancer cells (ionizing radiation, most chemotherapeutic agents and some targeted therapies) work through either directly or indirectly generating reactive oxygen species that block key steps in the cell cycle. As mesenchymal cancers evolve from their epithelial cell progenitors, they almost inevitably possess much-heightened amounts of antioxidants that effectively block otherwise highly effective oxidant therapies. Also key to better understanding is why and how the anti-diabetic drug metformin (the world's most prescribed pharmaceutical product) preferentially kills oxidant-deficient mesenchymal p53(- -) cells. A much faster timetable should be adopted towards developing more new drugs effective against p53(- -) cancers.

PMID:: 23303309; [PubMed - indexed for MEDLINE]
PMCID:: PMC3603456

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2016 Apr 27. [Epub ahead of print]

Combinational strategies of metformin and chemotherapy in cancers.

Zhang HH1, Guo XL2.

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Chemotherapeutic regimens are the most common treatment to inhibit tumor growth, but there is great variability in clinical responses of cancer patients; cancer cells often develop resistance to chemotherapeutics which results in tumor recurrence and further progression. Metformin, an extensively prescribed and well-tolerated first-line therapeutic drug for type 2 diabetes mellitus, has recently been identified as a potential and attractive anticancer adjuvant drug combined with chemotherapeutic drugs to improve treatment efficacy and lower doses. In this review, we summarized the molecular mechanisms underlying anticancer effects of metformin, which included insulin- and AMPK-dependent effects, selectively targeting cancer stem cells, reversing multidrug resistance, inhibition of the tumor metastasis and described the antineoplastic effects of metformin combined with chemotherapeutic agents in digestive system cancers (colorectal, gastric, hepatic and pancreatic cancer), reproductive system cancers (ovarian and endometrial cancer), prostate cancer, breast cancer, lung cancer, etc. Moreover, the clinical trials regarding metformin in combination of chemotherapeutic drugs were presented and the clinical obstacle or limitation related to the potential role of metformin in cancer treatment was also discussed in this review.