While it's too early to say what role, if any, COX-2 may play in these brain tumors, the researchers say the findings open up the possibility of future human trials examining the effectiveness of drugs to block the enzyme's activity in treating the diseases.
According to Adam Dicker, M.D., Ph.D., associate professor of radiation oncology and director of the Division of Experimental Radiation at Jefferson Medical College of Thomas Jefferson University in Philadelphia, there are no effective drugs to treat meningioma, one of the most common brain tumors (3 to 6 cases per 100,000 persons), and pituitary tumors known as pituitary macroadenomas. Surgery and radiation are somewhat effective, but both diseases frequently return after treatment. Few molecular targets for drugs for these diseases are known. Dr. Dicker wondered if COX-2, which is known to be in higher-than-usual amounts in some tumors, was present in an "up-regulated" or extremely active state in these types of tumors and might potentially be such a drug target. COX-2 is also known to enhance the effects of radiation and chemotherapy on some tumors.
Dr. Dicker notes that the tumors are very different. Meningiomas can grow to large sizes and cause various symptoms, whereas pituitary tumors are benign and more likely to cause hormonal imbalances in the body, and in some cases, visual problems.
In one study, Dr. Dicker, Lawrence Kenyon, M.D., Ph.D., assistant professor of pathology, anatomy and cell biology at Jefferson Medical College and their co-workers examined tumor samples from 83 patients with meningioma. They found that COX-2 expression is higher than normal in the tumors, and what's more, the greater the amount of enzyme present, the more aggressive the disease. "This is the first time anyone has looked at meningiomas and found this correlation of progression of disease," Dr. Dicker says. In a second study, Drs. Dicker and Kenyon and their colleagues examined 35 samples from patients with benign macroadenomas. They also found that the tumors overexpressed COX-2. Pituitary tumors with high levels of COX-2 also showed high levels of thyroid-stimulating hormone, which plays a role in hyperthyroidism. The results of both studies will be presented separately on May 21 at the annual meeting of the American Society of Clinical Oncology in Orlando. Dr. Dicker believes these findings may represent new opportunities for designing potential therapies for brain tumors. He says future clinical studies will look at the effectiveness of COX-2 inhibitors alone or in combination with radiation therapy on these types of brain tumors. Dr. Dicker will be involved in a trial currently being planned by the Radiation Therapy Oncology Group, a federally funded cancer clinical trials group that carries out multi-disciplinary oncology research nationwide, looking at COX-2 and other targeted therapies against meningioma.
Editors: This information is embargoed for release May 21 at 12 p.m. at the annual meeting of the American Society of Clinical Oncology in Orlando. (Abstract nos. 294 and 296)