AICR Researchers Studying Impact of Diet on Cancer Treatment Laboratory Studies Reveal How Components of Diet Help Therapies Target Cancer Cells WASHINGTON, DC In a series of recently published papers including studies now appearing in the July 2006 issues of two separate scientific journals American Institute for Cancer Research (AICR) grantee Gilda Hillman, Ph.D. has shown that under certain conditions, soy makes prostate cancer cells more sensitive to radiation therapy. Dr. Hillman is part of a growing movement of scientists investigating how dietary factors might improve the treatment of cancer. In labs and clinics across the country, many AICR researchers like Hillman are investigating how specific changes such as adding soy, garlic, fish oil or other foods to the diet may make it easier for conventional cancer therapies to target cancer cells, rendering treatment more safe and effective. The process of making tumors more susceptible to the effects of therapy is called sensitization. It appears that specific foods or food components have the potential to make cancer cells more radiosensitive (susceptible to radiation) or chemosensitive (susceptible to chemotherapeutic agents). Dr. Hillman has developed several cellular and animal models to study the interaction of soy and cancer therapy at the Karmanos Cancer Institute at the Wayne State University School of Medicine in Detroit, Michigan. Dr. Hillman’s work revealed that a combination of soy and radiation therapy is more effective against prostate cancer cells in laboratory experiments than radiation therapy alone. Dr. Hillman began looking at the issue of cancer treatment by studying the radiosensitization effects of genistein, a single soy component. But when her experiments revealed that under specific conditions, isolated genistein showed a troubling potential to stimulate the spread of tumor cells (metastasis) from prostate tumors to lymph nodes, Dr. Hillman switched to a dried powder of whole soy. She found that whole soy produced the same positive effects of genistein (radiosensitization) without the negative effect on tumor spread. “It’s intriguing that whole soy did not stimulate prostate cancer cells to metastasize while a single soy component did,” said Hillman. “We’ve confirmed it in different prostate cancer models, we’ve pinpointed the likely biomolecular mechanism responsible, and we are beginning to incorporate our findings into ongoing clinical trials with prostate cancer patients under rigorously controlled conditions with fellow Karmanos clinicians Dr. Omer Kucuk and Dr. Jeffrey Forman.” Initial Findings With Isolated Genistein Aroused Concern In a paper featured in the July 2006 issue of online scientific journal BMC Cancer, Dr. Hillman and her colleagues report that genistein alone seems to work in vitro by inhibiting a protein called Nuclear Factor Kappa B (NF-ęB), which is activated to help cells recover from damage, such as the kind of damage that occurs when cancer cells are exposed to radiation treatment. (This study provides strong confirmation of previous findings by Dr. Hillman’s colleague, Dr. Fazlul Sarkar.) In fact, Hillman and her colleagues determined the optimal dose and timing to maximize this anti-cancer effect in vitro. Cancer cells exposed to genistein before and after radiation therapy show the strongest likelihood to have their growth arrested during a phase of the life cycle just prior to cell division during which cells are known to be most susceptible to radiation. In another paper appearing in the July issue of the journal Radiation Research, Hillman and her colleagues have found that this combination of genistein and radiation therapy is effective against different models of prostate cancer in mice. Treating established prostate tumors with genistein first, followed by radiation, and finishing up with continuous treatment with genistein, effectively controlled tumor growth. The combination inhibited the growth of prostate tumors and kept cancer from spreading to lymph nodes. Dr. Hillman found, however, that pairing genistein with radiation therapy was crucial. In mice that were fed pure genistein alone, without undergoing radiation therapy, the soy phytochemical seemed to increase the rate at which prostate tumors spread to the lymph nodes. “The increase in metastatic spread observed with pure genistein given alone concerned us, because we needed to establish that any participants in clinical trials with soy would not be exposed to risks, no matter how small,” she said. The finding was of particular interest to Dr. Hillman’s colleague Dr. Omer Kucuk, who had previously shown that soy components such as genistein could be safely administered for more than 6 months in Phase I clinical trials. Whole Soy Provides Benefits Without Risks, Study Finds Dr. Hillman and her colleagues repeated their prostate cancer experiments using soy powder a dried form of whole soy instead of the isolated genistein soy component. They observed that soy exhibited the same anti-cancer effect: it sensitized prostate cancer cells to the effects of radiation by halting cellular growth. Importantly, feeding whole soy was not associated with the increased metastasis of cancer into the lymph nodes that was observed with genistein, even when whole soy was administered by itself, without radiation treatment. These findings were published earlier this year in the journal Radiotherapy and Oncology and in the Proceedings of the American Association for Cancer Research. “This is an important finding with great promise for people undergoing prostate cancer treatment,” said Dr. Hillman. “But this work is just beginning, and it is still too early to make practical recommendations about soy foods and soy supplements to cancer patients.” Diet as Combination Therapy? In addition to its ongoing mission to support research on diet and cancer prevention, AICR also provides funding for researchers exploring the interaction of conventional cancer therapies and a host of dietary factors, including: Quercetin (a phytochemical found in apples and onions) Glutamine (an amino acid found in meat, fish, beans, dairy) Curcumin (a component of turmeric, mustard, curry powder) Selenium (a mineral found in many plants and animals) Silymarin and Silibinin (both from the plant known as milk thistle) Vitamin D (from dairy foods) Phytic Acid (found in berries, seeds, broccoli) Fish Oil Garlic Hundreds of researchers are now investigating diet’s role during the very specific set of conditions that occur during cancer treatment. They are finding evidence that common dietary components can help conventional therapy halt cancer growth, cut off blood supply to tumors, prevent cells from spreading to other areas of the body, or simply encourage cancer cells to “commit suicide.” Their work suggests that dietary factors may soon come to be regarded as vital parts of cancer treatment and recovery tools to be employed with precision and care. Treatment And Prevention Not the Same But Hillman is quick to point out that findings from research on diet during cancer treatment do not speak directly to cancer prevention. “With cancer patients, we have a clearly defined and measurable goal get rid of the cancer. We can quantify the cause and effect relationship between dietary factors and existing tumors under specific sets of conditions, and repeat those experiments to verify our results.” Because many different but interconnected factors influence cancer risk, and these factors take place over a lifetime, it’s more difficult for scientists who study cancer prevention to isolate the effects of specific dietary factors. In order to arrive at scientific consensus about the prevention of cancer, researchers instead pool many different studies of varying design to find commonalities among population, laboratory, and clinical data. [Note: The advice for lowering cancer risk from the cancer prevention experts at AICR includes eating a varied diet rich in vegetables, fruit, whole grains and beans and low in animal fat, getting regular physical activity, and maintaining a healthy weight.] Promising Research, but Still Preliminary Dr. Hillman cautioned individuals who are currently undergoing prostate cancer therapy against loading up on soy foods or soy supplements without alerting their oncologists. More clinical data in human subjects are needed before advice about soy and supplements during treatment can be made, she said. She noted that participants in clinical trials are only exposed to soy in forms and amounts that are rigidly controlled by researchers, unlike individuals who consume whole soy foods or unregulated, store-bought soy supplements. “The phytochemical profiles of whole foods vary widely, as do the components of supplements available commercially,” said Hillman. “That’s another reason we can’t yet generalize our results to the world at large.” Until these ongoing clinical trials are completed, Dr. Hillman said, prostate cancer patients should always keep their doctors fully informed about their diet. “It’s clear that dietary factors can play a very important role perhaps never more important than during cancer treatment,” Hillman said. “It’s our goal to find ways to make this often painful and debilitating process less toxic, and more effective.” PRESS RELEASE For additional information please contact: Glen Weldon, 202-328-7744, 312 Release Date: June 28, 2006 Remember we are NOT Doctors and have NO medical training. 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