Molecular Therapeutics Advance Fight Against Brain Cancer

Through enhanced magnetic resonance imaging (MRI), newer and broader information is helping to better guide tumor removal. MRI is used to measure the anatomy and metabolism of tumors. This informs surgeons pre- and post-operatively with a three-dimensional map of tumor-associated blood flow to more precisely assess the full extent of tumor growth versus conventional imaging methods. "This novel approach helps guide surgery and assessment of treatment response," says Donald M. O'Rourke, M.D., Associate Professor of Neurosurgery. These novel imaging methods are leading to increased patient survival by allowing for greater tumor removal in a safe manner.

Neuroscientists are also ushering in a new era in which genetics will dictate treatment. In the 1990s researchers noted that a more favorable prognosis in patients with certain brain tumors, primarily oligodendrogliomas, was associated with a deletion of genes on chromosomes 1 and 19. This genetic loss translates into a significant life-expectancy gain for some patients and is therefore a robust predictor that post-surgery chemotherapy should be given to such patients.

Patients with the genetic deletion on chromosome 1 have a median survival in certain cases of about 10 years and respond particularly well to chemotherapy given immediately after surgery. Patients with the deletion have slower-growing tumors and show a better response to chemotherapy; whereas, those without the deletion have relatively faster-growing tumors and are less responsive to chemotherapy, so radiation therapy is required sooner. "Given the expected increase in the life-span of patients with this deletion, there is no need to give radiation therapy early in their treatment," explains O'Rourke.

The deletion can only be detected by genetic analysis. "Under the microscope these tumors can look identical, so there's no way of knowing the difference unless a genetic analysis is performed," explains O'Rourke.

Having the ability to provide such genetic testing to determine treatment is of benefit to patients. "The idea of using a genetic test to predict prognosis and select therapy, thereby deferring potentially deleterious treatment is tremendously attractive," says O'Rourke. "Penn's genetic testing is done in-house, so patients don't have to wait for the results." Further, there is no cost to the patient at this point since the tests are performed by the Neuro-oncology Program and supported by the Abramson Cancer Center at Penn. In addition, there is no requirement for additional blood samples, so results will be given more quickly with no need for follow-up visits.

Penn colleagues J. Carl Oberholtzer, MD, PhD, Department of Neuropathology and Myrna Rosenfeld, MD, PhD, Department of Neurology and Director of the Division of Neuro-oncology as well as Jaclyn Biegel, PhD, Director of Cytogenetics, Children's Hospital of Philadelphia, collaborated with O'Rourke on developing the genetic testing program. Dr. Biegel's laboratory performs the genetic test and has significant experience with genetic testing of brain tumors.

O'Rourke is also Director of the Human Brain Tumor Tissue Bank at Penn, one of only a few such dedicated banks in the United States. Tissue banks allow for the direct evaluation of human tumors and are one of the best ways to advance treatment options for gliomas and other human cancers. O'Rourke's basic research interests include finding new treatments for gliomas based on genetic alterations detected in tumors. He is currently investigating a variant of the epidermal growth factor receptor that is present in many primary glioblastomas to better understand the development of malignancy in the brain and how it relates to cancer cell division, survival, and movement.