Cancer cells sugar addiction, scientists find chemical responsible By Jackie Ho March 1, 2013 Scientists have found an explanation

why certain cancer cells are able to reprogram their metabolism and adapt for survival, even after their favorite food source is taken away. The report, released by the journal Cell, provides a new explanation and deeper understanding of the metabolic processes of tumor cells. Scientists say the evidence may provide a new opportunity for certain cancer therapies and treatments. For decades, tumor cells dietary and digestive characteristics have been a key area of research in scientists attempt to develop more innovative and effective cancer treatments.1 Many scientists have tried killing cancer cells by taking away its favorite food a sugar called glucose.2 However, that method has not only failed to kill cancer cells, but evidence has shown that glucose-starved tumors actually become increasingly aggressive by adapting to their environment and turning to other nutrients for survival. Scientists say this new study answers the long-studied paradox of glucose-starved tumors increased aggression. This new experiment also shows that depriving tumors of glucose should actually not be ruled out as a method for cancer treatment, so long as a particular enzyme (PKC) is present in the cancer cells. The new evidence shows that if tumor cells are deficient of this particular enzyme, the more likely they are to reprogram their metabolism and survive through alternative food sources. In other words, researchers found that cells with high levels of the enzyme continue to rely on their favorite food, glucose, whereas cells with low levels of the enzyme search for other sources of energy and survival. Scientists said that glucosedeprivation cancer treatments might have failed in the past if this particular enzyme was not present. Jorge Moscat, Ph.D, lead researcher of this study and a professor in SanfordBurnhams National Cancer Institute-designated Cancer Center, said, If we can find an effective way to add (the enzyme) back to tumors that lack it, wed make them less suited for survival and more sensitive to current therapies. He said Oncogene. (2012, January 21). Qs next: The diverse functions of glutamine in metabolism, cell biology and cancer. Retrieved from http://www.nature.com/onc/journal/v29/n3/full/onc2009358a.html 2 The Journal of Experimental Medicine. (2012, February 13). Targeting glucose metabolism for cancer therapy. Retrieved from http://jem.rupress.org/content/209/2/211.abstract
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this new study may lead to innovations in glucose-deprivation cancer therapies and treatments. Experts not involved with the study also said the findings are significant because they have important implications for certain cancer treatments that heavily involve the supply of glucose. Raul Mostoslavsky, M.D., Ph.D., of the Massachusetts General Hospital (MGH) Cancer Center, has said his research indicates that, at least in certain cancers, inhibiting cells use of glucose for their metabolism could provide a strong alternative to halt cancer growth, possibly acting synergistically with current antitumor therapies.3 Robert J. Gillies, Ph.D., chair of the Department of Cancer Imaging and Metabolism at Moffitt Cancer Center, said glucose metabolism is a crucial part of cancer cells survival. The vast majority of malignant tumors metabolize glucose at high rates, Gillies said. We have proposed that there is a direct, causative link between increased glucose metabolism and the ability of cancer cells to invade and (spread).4 In this study, the researchers, from the Sanford-Burnham Medical Research Institute, tested both human intestinal tumor cells and mouse colon cancer cells with various levels of the enzyme. They found that cells without the enzyme were able to reprogram their metabolism to use alternative sources of energy. Researchers said that the enzyme kept the cells addicted to glucose, but without it, the tumors were able to survive in conditions that would otherwise be deadly. Moscat said although he looked specifically at colon cancer in this study, his findings are likely also true for other tumor types. However, other scientists have said that cancer cell metabolism needs to be studied respectively for each unique type of cancer cell, as opposed to assuming that findings for one type of cancer cell can apply to all types of cancer cells. Chi V. Dang, M.D., Ph.D., Director of the Abramson Cancer Center (ACC), has said, The complex regulatory networks involving cancer genes and metabolic pathways need to be defined for specific cancer types so the targeting of cancer cell metabolism could be strategically guided by (genetic changes) in cancers.5 Cell. (2012, December 7). The Histone Deacetylase SIRT6 Is a Tumor Suppressor That Controls Cancer Metabolism. Retrieved from http://www.sciencedirect.com/science/article/pii/S0092867412013517 4 Cancer Research. (2013, January 25). Tumor cells engineer acidity to drive cell invasion, Moffitt Cancer Center researchers say. Retrieved from http://www.moffitt.usf.edu/ 5 Genes and Development. (2012). Links between metabolism and cancer. Retrieved from http://genesdev.cshlp.org/content/26/9/877.full
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This study only explains one phenomenon in one kind of cell. Theres lots of other factors involved, said Young D. Kim, M.D., chair of the Department of Anesthesiology at Georgetown Hospital. If scientists can find a way to add this enzyme to cancer cells without it, this might be a breakthrough. But theres a long way to go, Kim said.