There is a critical need to develop new drugs to treat central nervous system tumors, but progress toward drug development has been slow. This is because of the potential side effects of drugs entering the brain and the difficulty getting drugs to cross the blood-brain barrier (a “wall” that protects the brain by pumping toxins out of brain tissues and back into the blood stream).
Many of the components, equipment, and expertise needed to develop a pipeline for brain tumor drug development are in place at Memorial Sloan-Kettering Cancer Center.
Brain cancer expert Eric Holland reports on efforts to develop new drugs that block genes involved in the formation of brain tumors.
Work undertaken through the Brain Tumor Center is firmly grounded in basic studies of the fundamental properties that drive tumor development and growth. Pilot grants are awarded to investigators currently at Memorial Sloan-Kettering Cancer Center who are conducting basic studies in this area. We are also recruiting new investigators who have a proven interest in brain tumor biology.
Preclinical Cancer Biology
A critical step in the development of new therapies is ensuring that they produce their desired effect in animal models. A unifying component of the work must be the continuous observation of biological processes in the living body (in vivo) for translation to the clinical setting. The Brain Tumor Center is involved in the development of genetically engineered mouse models of gliomas and medulloblastomas for study by our investigators and their colleagues at Memorial Sloan-Kettering.
Imaging is used to monitor tumors before, during, and after treatment to assess therapeutic response. Many kinds of non-invasive imaging methods are available to investigate tumor physiology and metabolism. These include magnetic resonance imaging, positron emission tomography, and bioluminescence imaging, which can provide complementary information related to tumor detection and the monitoring of early therapeutic responses. The imaging methods selected will, in part, be based on the nature of the therapy tested and the parameter(s) to be investigated.
Translational studies is the process by which research on potential new targets and therapies make the transition from animal experimental models to humans. To streamline this process, the Brain Tumor Center maintains a brain tumor and serum bank, which enables neuro-pathologists to conduct analyses and identify predictive or diagnostic tumor markers.
The Center's investigators work with members of the Human Oncology and Pathogenesis Program (HOPP), the Memorial Hospital-based program focused on translational research.
Memorial Sloan-Kettering is a national leader in evaluating experimental compounds in clinical trials for all types of cancer, including brain tumors. These research studies test how well new medical approaches work in people, and evaluate new methods of screening, prevention, diagnosis, or treatment.
The goal of the Brain Tumor Center's clinical research component is to combine the efforts of laboratory and clinical investigators and develop new drugs to improve the way we prevent and treat brain tumors.
Many of these therapies are developed in the lab under the guidance of our neuro-oncologists with the express intent of testing them in clinical trials at Memorial Sloan-Kettering. Many of these trials have surgical components — i.e. the drugs are given for a week prior to surgical removal of a brain tumor — and the effects of the drugs are measured in the tumor samples that are removed. See the clinical trials section for information on current brain tumor clinical trials.
At the Brain Tumor Center, our research molecular profiling panel includes a number of cutting-edge tests developed recently in the laboratories of faculty members Jason Huse, Cameron Brennan, and Ingo Mellinghoff.
The tests are designed to simultaneously profile an array of biomarkers that recent research indicates are of likely importance to both prognosticate disease outcome and stratify patients into treatment-relevant subgroups. We have now applied our panel to almost 90 samples.
The tests are functioning in real time, profiling specimens as they are removed from patients undergoing brain surgery at Memorial Sloan-Kettering. In addition, automated computational pipelines have been developed internally to generate refined reports harboring already-interpreted data. We are now poised to greatly advance our capability as an institution to perform molecularly driven trials.
Brain Tumor Tissue and Serum Bank
Within our centralized Brain Tumor Center, faculty are diligently working to make innovative scientific advancements, perform clinical trials, and achieve the molecular profiling of tumors. The development of the Brain Tumor Tissue and Serum Bank paired with a fully annotated, customized clinical database is the backbone of much of our current and future work.
More than 1,000 brain tumor specimens, which largely include corresponding blood samples, have been collected to date, along with the full history of every patient who has come to Memorial Sloan-Kettering for brain tumor treatment in the past four years. Investigational molecular tumor profiling is fed into our database and joined with standard molecular tests done by clinical pathology.
Clinical data on all brain tumor patients from 2007 to 2011 has been captured and all consented glioblastoma multiforme patients have molecularly profiled tumor data captured. Together, this dataset is invaluable for driving translational research and laying the groundwork for personalized, targeted therapy of brain tumors stratified by subtypes.