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Cleveland Clinic Researchers Identify Differences in Growth Mechanisms of Cancer Cells and Normal Cells

Monday, Dec. 8, 2008, Cleveland:
Cleveland Clinic researchers today presented findings that suggest cancer could be treated in a novel way that is much less toxic.

The researchers found that they could alter an existing chemotherapy drug to stop the growth of cancer cells and encourage the growth of healthy cells. Current treatments kill both cancer cells and healthy cells, which leads to numerous side effects.

The results of the studies suggest that the mechanisms that cause cancer cells to divide and grow uncontrollably are often different from the mechanisms that drive the growth of healthy stem-cells. This difference can be exploited to selectively stop the growth of the cancer cells without stopping the growth of healthy stem-cells.

"Today, most cancer chemotherapy works the margins - the chemotherapy is marginally more poisonous to cancer cells than normal cells," said lead investigator Yogen Saunthararajah, M.D., of Taussig Cancer Institute at Cleveland Clinic. "Therefore, treatment is difficult and risky for patients and can only be given for a few days at a time, with long periods without treatment during which the cancer can regrow."

"We are excited that we can modify the use of existing drugs to [stop the growth of cancer cells and encourage the growth of healthy cells], which will allow us to start clinical trials soon." - Yogen Saunthararajah, M.D.

"Using this alternative approach, which in the test-tube has opposite effects on cancer cells versus healthy stem-cells, perhaps therapy can be given regularly and for longer periods, to get the maximum benefits out of treatment. We are excited that we can modify the use of existing drugs to produce this effect, which will allow us to start clinical trials soon."

The results were presented Monday at the annual meeting of the American Society of Hematology (ASH) in San Francisco.

The research team studied bone marrow samples of myelodysplastic syndrome (MDS) and leukemia patients as well as healthy blood stem-cells to discover that the enzyme known as DNMT1 plays opposite roles in the healthy stem-cells versus the cancerous cells. Therefore, inhibiting the function of this enzyme produced opposite effects on the healthy cells versus the cancerous cells. The drug used to inhibit this enzyme, decitabine, is already available for clinical use, allowing for clinical studies to be conducted in the next year to determine if using decitabine in this new method can reproduce the effects seen in the test-tube in patients.

The research team emphasized that this work needs to undergo the peer review process and publication and that clinical trials must be conducted to further test this approach in patients. This study is also scheduled to be highlighted as a "Best of ASH" presentation by the American Society of Hematology, the world’s largest professional association of blood specialists.

Cleveland Clinic Researchers Publish
First Comprehensive Study on New Cancer Grouping

Thursday, Oct. 23, 2008, Cleveland: Cleveland Clinic researchers have published the results of the first study to track the treatment patterns used by physicians who care for patients with myelodysplastic syndromes (MDS). MDS, which was once considered an orphan disease, is now considered a cancer mainly affecting the elderly. The Surveillance, Epidemiology and End Results (SEER) database has tracked MDS for seven years, but little has been known about how MDS patients have been treated for their disease, or the characteristics of these patients, until now.

To learn more about MDS, Mikkael Sekeres, M.D., of Cleveland Clinic’s Taussig Cancer Institute, and a team of researchers surveyed 101 geographically-representative physicians who treat MDS patients to develop a detailed overview of the disease and current treatment methods. They then reviewed data on 4,514 patients seen by these physicians.

"It is our hope that this information will help physicians learn more about this little-known cancer grouping and will ultimately assist researchers and clinicians as they try to develop more effective treatments and therapies for MDS," Dr. Sekeres said. "This research is just the beginning of the process into understanding MDS, but we’re excited about this first step and what could come from it."

Currently, the only known cure for MDS, which occurs when blood stem cells do not mature into healthy red and white blood cells and platelets, is bone marrow transplantation, yet the study found that few patients are considered for this treatment. The findings also revealed that a high number of the patients were treated with red blood cell or platelet transfusions, and more than half of the patients received red blood cell stimulating agents. Additionally, the majority of higher-risk patients have been treated with a combination of stimulating drugs and other medicines, even though these combinations are still being clinically tested. The research also showed that few MDS patients are considered for clinical trials.

There are an estimated 12,000 to 15,000 new MDS cases diagnosed annually in the United States, and the estimated worldwide prevalence ranges from 300,000 to 400,000 cases. Due to the growing risk of this disease with advancing age, its prevalence is rising as life expectancy rises.

The study is being published in the November 5, 2008 issue of the Journal of the National Cancer Institute.