Wednesday, April 22, 2009
Study identifies key molecular mechanism involved in process, paves way for possible treatments
Drinking alcohol is a known risk factor for many types of cancer, but studies also have shown that moderate alcohol consumption may actually decrease the risk of developing certain cancers, such as lymphoma. Now, researchers at the University of Maryland Marlene and Stewart Greenebaum Cancer Center have identified a molecular mechanism that helps to explain how alcohol protects against non-Hodgkin’s lymphoma, the most common form of lymphoma.
The scientists report in an online edition of the journal Blood that low-dose, chronic exposure to ethanol – regardless of whether the source is beer, wine or other types of alcoholic beverages – inhibits the activity of a protein called mTOR. That protein plays a key role in controlling important cellular processes, including the regulation of cell growth. The researchers found that the equivalent of several drinks a day resulted in “a striking inhibition of lymphoma growth” in mouse models.
“We’re not saying that people should have a couple of drinks a day to reduce their risk of developing lymphoma. But we believe that having a better understanding of this process may lead to more effective, targeted therapies to treat lymphoma and possibly prevent it. We hope to develop new compounds that will mimic the effect of alcohol, targeting the molecules that interact with this master regulatory molecule,” says Ronald B. Gartenhaus, M.D. , the study’s senior author.
Dr. Gartenhaus, an associate professor of medicine at the University of Maryland School of Medicine and a researcher at the University of Maryland Marlene and Stewart Greenebaum Cancer Center, is continuing his research into lymphoma development, searching for other molecules involved in mTOR inhibition. “We’re looking to develop very potent inhibitors of these molecules that will serve the same purpose as alcohol, only better,” he says.
The results of the study are available online in a First Edition of Blood, which is published by the American Society of Hematology. To see an abstract of this study, visit: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/blood-2008-11-191783v1
E. Albert Reece, M.D., Ph.D., M.B.A., vice president for medical affairs, University of Maryland, and dean of the University of Maryland School of Medicine, says, “Lymphoma is a major hematological malignancy associated with considerable morbidity and mortality. These findings significantly advance our understanding of how lymphomas develop and offer clues that may lead to the development of new therapies. The fact that Blood, the most cited peer-reviewed publication in the field, decided to publish these results underscores the importance of the findings.”
Lymphoma is a cancer that originates in the lymphocytes (a type of white blood cell) of the immune system. About 74,000 Americans are diagnosed with lymphoma each year. There are two major categories of lymphoma: Hodgkin’s lymphoma and non-Hodgkin’s lymphoma. Most non-Hodgkin’s lymphomas are B-cell lymphomas, but there are other lymphomas that arise from T cells or NK cells. Lymphomas can be slow-growing or aggressive, and more aggressive non-Hodgkin’s lymphomas usually are treated with chemotherapy and a biological therapy such as the monoclonal antibody Rituxan. On occasion, radiation therapy is also utilized. Bone marrow or stem cell transplantation may also be a treatment option.
Dr. Gartenhaus notes that a number of epidemiologic studies have found evidence that people who drink moderate amounts of alcohol – regardless of the beverage – have a decreased risk of having most types of non-Hodgkin’s lymphoma. But researchers had not been able to pinpoint the exact reason for this phenomenon. “We were able to demonstrate in our study that low-dose, chronic exposure to ethanol
disrupts the mTOR signaling pathway in lymphocytes, significantly inhibiting the growth of
lymphoma tumor cells. Our findings underscore the critical role of mTOR signaling in lymphoma,” Dr. Gartenhaus says.
mTOR, which stands for mammalian target of rapamycin, is known to be involved in the
development of certain cancers, in particular those caused by a mutation in the PTEN gene. mTOR
inhibitors are used to help prevent rejection of transplanted organs, but because of the growing evidence of a link between mTOR and cancer, researchers are now studying mTOR inhibitors as possible cancer treatments.
Patrick R. Hagner, a graduate research assistant at the University of Maryland School of Medicine and the study’s lead author, says the study looked at the effect of alcohol on both breast cancer cells and lymphoma cells. “What we found is that the alcohol did not suppress the mTOR signaling pathway in breast cancer as it did in lymphoma, which was consistent with previously published clinical findings demonstrating a protective effect of moderate alcohol consumption on lymphoma development in contrast to the opposite effect for breast cancer,” he says.
The University of Maryland Marlene and Stewart Greenebaum Cancer Center, a National Cancer Institute-designated cancer center, is part of the University of Maryland School of Medicine and the University of Maryland Medical Center. The cancer center offers a full range of treatments for all types of cancer and has a very active cancer research program.