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CTRC melds medicine and research in cancer crusade

March 2011

by Elizabeth Allen

What is translational science? Translational science is the process by which experiments in laboratories become the medicines that help the people we love.

At the Cancer Therapy & Research Center (CTRC) at the UT Health Science Center San Antonio, academic professionals work side by side transforming research into real remedies.

Two types of academic professionals work at the CTRC. One is the basic scientist, dedicated to understanding the fundamental process of cancer growth, exploring the smallest details of how a normal cell transforms into a cancer cell. The other is the academic physician working with patients in the clinic, being the first to test the newest ways to prevent, detect or treat cancer.

But at the CTRC, the labels "basic scientist" and "clinician" no longer apply, said Ian M. Thompson Jr., M.D., the CTRCís director. They are one team, forming working groups from the labs and the clinics, crossing a range of cancers such as breast, colon, lung and prostate.

"They are focused on the concept of translational science," he said, "putting the question to basic science advances: ĎHow can we use this discovery to prevent, diagnose, or treat cancer in a better way?í"

Thatís the philosophy that brought Pothana Saikumar, Ph.D., before a gathering of breast cancer clinicians to discuss findings he made with postdoctoral fellow Prajjal Singha, Ph.D. Drs. Saikumar and Singha are researchers in the Department of Pathology in the Graduate School of Biomedical Sciences.

Invited by Peter Ravdin, M.D., Ph.D., director of the CTRCís Comprehensive Breast Health Clinic, Dr. Saikumar explained how the pathologists uncovered a clue in a longstanding cancer paradox that shows promise for treatment of some of the most aggressive breast cancers.

Scientists have long known that a small protein Dr. Saikumar was studying, Transforming Growth Factor-Beta (TGF-B), behaves in a paradoxical way. When a cell begins undergoing the transformation into a cancerous state, TGF-B can stop that growth and protects us from developing cancer. But if that cell escapes the TGF-B surveillance, then it will advance into a full-blown cancer cell and TGF-B can help it thrive and spread faster.

"Turning off this Ďtreasonousí action of TGF-B alone may indeed be advantageous," the pathologist said.

Dr. Saikumar and Dr. Singha found a clue in an obscure protein called TMEPAI, and discovered that the two proteins work together to affect cancerís growth and spread. When they knocked down the gene, thus blocking TMEPAI protein expression, the cancerous cells behaved as if they were almost normal. And yet the good work TGF-B does in the body had been preserved. Whatís more, the most profound changes were in so-called "triple-negative" breast cancers, those that require the most toxic chemotherapies.

Medical oncologist Richard Elledge, M.D., one of the breast cancer doctors who met with Dr. Saikumar, said the discovery has the potential to turn into a new cancer fighting strategy that could allow for the personalization of treatment according to a specific tumorís molecular biology. "A similar strategy has been successfully employed previously in breast cancer, with drugs that selectively block HER-2 protein overexpression," Dr. Elledge said.

Among the other CTRC researchers working to develop new knowledge and translate it into clinical practicality are Patricia Dahia, M.D., Ph.D.; Shou-Jiang Gao., Ph.D.; and Bin Zhang, M.D., Ph.D.

Dr. Dahia is an assistant professor of hematology and medical oncology in the School of Medicine, with a cross appointment to the Department of Cellular and Structural Biology, part of the Graduate School of Biomedical Sciences. Her research group identified a new tumor-suppressor gene tied to a rare, hereditary form of adrenal cancer.

Initially studying families affected by the disease, Dr. Dahia used the process of elimination to solve the puzzle of which gene was mutated to cause the problem. Nowshe is leading work on defining how the gene-tumor relationship works.

Dr. Gao, who shared with Dr. Dahia the CTRCís Discovery of the Year award, helped uncover how a tiny molecule helps Kaposiís sarcoma-associated herpesvirus survive in the body. Dr. Gao is a professor in the School of Medicine, holds the H-E-B Distinguished Chair for Cancer Research and heads the tumor virology program at the Greehey Childrenís Cancer Research Institute.

People with AIDS often develop the malignant cancer Kaposiís sarcoma, caused by the virus. Dr. Gao found that the virus hides within a healthy body by using one of its own microRNA molecules as a sort of thermostat. It tells the virus when to slow down and evade the healthy bodyís immune system, or, when it senses immune system weakness, when to replicate quickly and mount an offensive.

Dr. Zhang was awarded a $450,000 grant from the Ovarian Cancer Research Fund in October to continue his work in cancer immunotherapy ó using the bodyís own immune system to fight cancer. Immunotherapy research has been hobbled by the tumorís production of an enzyme that makes a substance that blocks anti-tumor T-cell (white blood cell) activity. Dr. Zhang was able to block the enzyme in a mouse model, improving T-cell function. Combining this with T-cell therapy, Dr. Zhang showed tumor-bearing mice can be cured.

The grant is for a translational study, Dr. Zhang said, and his goal is to take his immunotherapy to the clinical-trial level in patients in the next three years.

They are just a few of the scientists that Dr. Thompson spoke of when he said, "These passionate individuals, working in teams, are those who will continue the tradition of excellence at the CTRC."

Related Stories

Translational science in action
Dahia, Gao presented CTRC Discovery of the Year award

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