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Consultative Proteomics Service Can Help 'Outsmart' Hard-to-Treat Cancers

Collaboration with School of Health Information Sciences, M. D. Anderson aimed at individualized therapy

With the completion of the Human Genome Project, scientists now are turning their attention to the proteins produced by genes. This emerging field is called proteomics, and it’s the basis of a new cancer consultation service offered by the Department of Pathology and Laboratory Medicine at The University of Texas Medical School at Houston.

The Consultative Proteomics service, which started in July, analyzes the protein activity in patient tumors, providing information useful in prescribing treatments and determining the risk of recurrence.

The idea of Robert E. Brown, M.D., holder of the Harvey S. Rosenberg, M.D., Chair in Pathology and Laboratory Medicine at the UT Medical School, the service – which he believes is among the nation’s first – currently is limited to cancer patients who have exhausted conventional therapies or whose tumors do not qualify for an existing protocol.

Brown’s own research focuses on the signal transduction pathways in cells that give proteins their marching orders and that, when overactive, can con-tribute to cancer as well as diabetes, heart disease and other problems.

“We are trying to outsmart the cancer,” Brown said. “We are proposing to take signal transduction data and translate it into potential clinical treatments in collaboration with our clinical colleagues.”

Cancer is the second most common cause of death in the United States, exceeded only by heart disease. In 2007, about 559,650 Americans are expected to die of cancer – more than 1,500 people a day – according to the American Cancer Society. In the U.S., cancer accounts for one of every four deaths.

A Visionary

“Bob was always a visionary,” said Suresh Nair, M.D., a longtime colleague of Brown and the director of the Hematology Oncology Fellowship Program at Lehigh Valley Hospital and Health Network in Allentown, Pa. “I’ve always told him that he was 10 years ahead of his time.”

Brown’s service is based on a type of protein study called morphoproteomics and involves a visual inspection of proteins in malignant cells. He looks for changes in cellular location and state of activation of the proteins, which can help oncologists identify the vulnerable parts of malignant cells. “We are trying to understand the chemistry of what makes tumor cells grow and spread,” he said.

Recently, a morphoproteomics laboratory with quantitative digital imaging capability has been developed in the Department of Pathology and Laboratory Medicine.

“The objective, in the context of a patient with cancer, is to characterize the protein circuitry in an individual patient’s tumor for the purpose of exposing molecular targets amenable to specific therapeutic intervention,” Brown added.

Too new for long-term follow-up, Brown has anecdotal reports on the benefits of the studies. “I have great faith that Dr. Brown’s proteomic studies are going to become a standard way to direct cancer therapies in the future,” said Anne E. Bendel, M.D., pediatric hematologist/oncologist, Children’s Hospitals and Clinics of Minnesota, who has used Brown’s approach in treating two incurable cancer patients.

The consultative proteomics service stems from Brown’s work at the Geisinger Medical Center in Danville, Pa., where he studied signal transduction pathways in cancer cells and examined procedures in the laboratory to inhibit those pathways. “This signaling information can lead to processes that promote the growth, invasiveness, metastatic potential and resistance to conventional chemotherapy and radiation therapy of tumors,” he said.

Finding the Achilles’ Heel

Brown said the same pathways that sometimes facilitate cancer growth also are its “Achilles’ heel.” For example, one such Achilles’ heel of a tumor is its reliance on the nuclear factor kappa B pathway to render it resistant to traditional chemotherapy. “By deter-mining the state of activation of this pathway in a given tumor, we can direct therapy against this path-way at the same time we are using conventional therapy,” he said.

Application of morphoproteomics study to common cancer types, according to Amy Law, M.D., hematology/oncology at Geisinger Medical Center, can provide additional knowledge on the pathogenesis of cancer at the signal transduction pathway levels and lead to prognostic models. “We are not only appreciating the ‘static’ cancer under the microscope, but are able to appreciate the dynamics of the machinery behind that individual cancer cell,” Law said.

Individualized therapy for cancer patients using proteomics is a national initiative, with major pro-grams already at The University of Texas M. D. Anderson Cancer Center, the National Institutes of Health and others. “The future of cancer care is customized molecular medicine,” said Nair, who collaborated with Brown on the care of a soft tissue sarcoma patient involving rapamyacin to block pathways. “But, it is still developing.”

Bihong Zhao, M.D., Ph.D., an assistant professor of pathology and laboratory medicine at the UT Medical School and a member of the consultative proteomics team, noted there are multiple pathways in some cells, and when doctors block one pathway, another often arises. “There is a lot of information to process. We need bioinformatics to analyze it,” said Zhao, who believes computer modeling will become an integral part of morphoproteomics.

Brown is working with two members of the UT School of Health Information Sciences at Houston – Assistant Professor M. Sriram Iyengar, Ph.D., and Mary McGuire, a graduate research assistant – to develop computer-based mathematical and statistical models.

Dongfeng Tan, M.D., an associate professor of pathology at the M. D. Anderson Cancer Center, and his colleagues, are collaborating with Brown on morphoproteomic characterization of pancreatic ductal carcinoma.

Consultative proteomics reports are often covered by insurance and must be requested by a physician. For more information about this service, call  713-500-5332.

By Rob Cahill, Institutional Advancement

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