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This invention utilizes a novel paradigm for cancer therapy: induces apoptosis of targeted cells by creating a local deficiency of an essential nutrient.
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Background: Each year in United States, 300,000 men are affected by prostate cancer, 200,000 women are affected by breast cancer, and 100,000 individuals are affected by colon cancer. Over $15 billion is spent every year to treat these cancers alone. However, existing cancer therapies, which target rapidly proliferating cells, are toxic to patients. Also, standard chemo- and radiation therapy cannot eliminate quiescent cells in solid tumors, resulting in frequent relapses. Furthermore, drug-resistance mutations, over-expression of the bcl-2 gene (an anti-apoptotic oncogene), and loss of the p53 gene (a tumor suppressor gene) are causing some cancers to be strongly resistant to treatments. Applications: Cancer therapy; elimination of other unwanted cells. Advantages: • This invention utilizes a novel paradigm for cancer therapy: induces apoptosis of targeted cells by creating a local deficiency of an essential nutrient. • Efficiently eliminates hard-to-kill quiescent, bcl-2 over-expressing, or p53-deficient tumor cells. • No intrinsic toxicity. • Antidote available (vitamin B1). Technology: The present invention is based on the discovery that apoptotic cell death can be induced by creating a local deficiency in the natural vitamin, thiamin. This technology is applicable to cancer treatment and to eliminate other unwanted cells. For therapeutic use, localized depletion of thiamin will be achieved in vivo by targeted application of thiaminase (an enzyme which cleaves thiamin) to tumors, localized expression of the thiaminase gene, or use of targeted small-molecule thiaminase analogues. Furthermore, the method allows rapid reversal of the effects of the deficiency at any time such reversal is desired, simply by the administration of replacement thiamin. Our investigators have shown that a recombinant thiaminase, originated from the amoeba Naegleria gruberi, is remarkably stable and kills p53-null cancer cell lines in vitro. The many promising attributes of this new technology warrant its development into a major cancer therapeutic method of the future.