SAN ANTONIO (Dec. 5, 2013) — Support from the Max and Minnie Tomerlin Voelcker Fund is enabling UT Health Science Center at San Antonio researchers to study the biological basis of B-cell lymphoma, one of the most common and aggressive types of cancer. Findings from the lab are being shared with physicians of the Cancer Therapy & Research Center (CTRC) at the UT Health Science Center. The CTRC, site of many human clinical trials of new cancer therapies, is San Antonio’s only National Cancer Institute-designated Cancer Center.
In a recent online edition of the journal Blood, a team led by Ricardo C.T. Aguiar, M.D., Ph.D., associate professor of medicine and biochemistry in the School of Medicine at the Health Science Center, reported that high levels of a molecule called microRNA-155 result in loss of a tumor-suppressor gene, the retinoblastoma (RB) gene.
“Loss of RB is a critical and frequent event in development and progression of many cancer types,” Dr. Aguiar said. “The discovery that microRNA-155 controls RB was a surprising but very important finding because it helps explain how this microRNA may cause cancer.” He has a Voelcker Fund young investigator award of $750,000 over five years to continue the studies. Lymphomas are cancers that originate in the lymphoid cells of the immune system.
A dimmer
MicroRNA-155 is like a dimmer in a lamp that gives the right amount of light, Dr. Aguiar said. Abnormally high amounts of microRNA-155 may result in cancer, while abnormally low levels can lead to immune deficiency. Since microRNA-155 plays a broad role across multiple cancer types, fine-tuning this dimmer may result in a novel therapy for a large patient population, Dr. Aguiar said.
“Work in our lab is always geared toward clinical applications, including the development of more accurate diagnostic models and the design of new, less-toxic and more-effective treatments for B-cell lymphoma and related tumors,” he said. Kevin Kelly, M.D., and Steven Weitman, M.D., Ph.D., director of the CTRC Institute for Drug Development, are Dr. Aguiar’s clinical collaborators.
75,000 cases annually in U.S.
B-cell lymphoma is a common adult tumor, ranking sixth after prostate, breast, lung, colorectal and skin cancers. About 75,000 new cases are diagnosed in the U.S. annually. The microRNA-155 finding applies to multiple subtypes of lymphomas representing about 70 percent of the new cases diagnosed each year, Dr. Aguiar said. The disease is often incurable.
The most common type, known as diffuse large B-cell lymphoma, is especially difficult to treat and about half of patients still die of their disease, despite the best existing therapy. “Our new finding is a big clue as to how to improve these cure rates, because microRNA-155 is primarily deregulated in the fatal cases,” Dr. Aguiar said.
The paper will come out in print in Blood with an accompanying editorial, which is reserved for the most important papers in the field.
Diagnosing genetic changes
Earlier this year, support from the Voelcker Fund and the Cancer Prevention & Research Institute of Texas (CPRIT) led to another significant finding about lymphoma.
Dr. Aguiar and his team developed a novel approach to identify chromosomal translocations (transfer of genetic material from one chromosome to another), a hallmark of cancer cells. The team used this strategy to diagnose known genetic changes in lymphoma and discover several new ones.
Existing methods of discovering the chromosomal changes are labor intensive and biased toward known changes, the authors wrote in Blood. The team discovered a new method that readily identified three novel targets for development of potential therapies to treat lymphoma.
The group collaborated with the Department of Pathology in the School of Medicine and with colleagues at UT Austin.
The Cancer Therapy & Research Center (CTRC) at The University of Texas Health Science Center at San Antonio is one of the elite academic cancer centers in the country to be named a National Cancer Institute (NCI)-designated Cancer Center, and is one of only four in Texas. A leader in developing new drugs to treat cancer, the CTRC Institute for Drug Development (IDD) conducts one of the largest oncology Phase I clinical drug programs in the world, and participates in development of cancer drugs approved by the U.S. Food & Drug Administration. For more information, visit www.ctrc.net.