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Connecting Science and Clinical Practice: Brain Tumors

Howard A. Fine, M.D., Chief of the Neuro-Oncology Branch at NCI's Center for Cancer Research. Image credit: National Institutes of Health.

Howard A. Fine, M.D.
Chief of the Neuro-Oncology Branch
at NCI's Center for Cancer Research

Diagnosing Brain Cancer

NCI's Glioma Molecular Diagnostic Initiative (GMDI) aims to develop a comprehensive molecular classification system for this type of brain cancer, thus allowing consistent prediction of response to therapies for individual patients. The largest study ever conducted to merge genetic and clinical information, GMDI is a nationwide partnership of several NIH Institutes and NCI-funded consortia and scientists. GMDI investigators are conducting retrospective studies, which look backward to examine exposures to suspected risk, and prospective studies, which watch for outcomes over a long period of time, to build and validate molecular and genetic models of glioma. The molecular, genetic, and clinical data from GMDI are being compiled in REMBRANDT (REpository for Molecular BRAin Neoplasia DaTa), a publicly accessible online database and universal classification system.

Dr. Howard Fine "sees as many patients as want to see me." As the Chief of NCI's Neuro-Oncology Branch, he evaluates between 2,000 and 3,000 brain tumor patients a year. Brain cancer, he says, "is a disease that impacts patients physically, while eroding their cognition and personality, exacting a devastating toll on both the patient and caretaking families." Unfortunately, as Dr. Fine points out, "the current standard of care is not optimal." The disease is not amenable to prevention or early diagnosis, and care for brain cancer patients falls between the expertise of neurology and medical and surgical oncology. Dr. Fine is committed to changing that situation.

Gliomas are the most common tumors that originate in the brain, beginning in the cells that surround and support nerve cells. Patients with low-grade glioma, which tends to grow more slowly, have a survival rate that averages 5 to 10 years, while patients with high-grade, or aggressive, glioma (glioblastoma being most common) have a 14-month survival rate. The standard treatment for glioblastoma is surgery, radiation, and chemotherapy. Dr. Fine explains that glioblastomas are "hugely different" from patient to patient, which makes the case for a better understanding of the underlying genetic abnormalities that distinguish one type from another. Although several key genes have been shown to play a role in glioblastoma, and drugs that inhibit these targets have been developed, many other genes remain to be identified.

Dr. Fine envisioned an integrated program to study large numbers of glioma patients—comprised of 20 NCI-designated Cancer Centers, the pharmaceutical industry, brain tumor consortia, clinical trial cooperative groups, and other NIH Institutes. His concept, the Glioma Molecular Diagnostic Initiative, or GMDI, collects and correlates standardized data from tumor specimens that can be analyzed to identify patient genetic profiles and novel molecular targets—and to help develop patient-tailored therapy. For Dr. Fine, efforts such as this "represent a flagship initiative that brings together divergent programs in a war that couldn't be won otherwise."

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