Primary brain tumors are tumors that arise inside the brain. They are distinguished from secondary brain tumors, which are cancers that spread (metastasize) to the brain from other areas of the body such as the breast or lung.
Certain types of primary brain tumors, such as meningiomas, which originate in membranes lining the brain, can be successfully resected by surgery. However, a large portion of brain tumors arise from glial cells, which are support cells for neurons.These tumors, commonly known as gliomas, are highly lethal, as tumor cells typically disperse throughout healthy brain tissue, which makes complete surgical resection impossible. The blood-brain barrier, which shields the brain from most available cancer drugs, poses another obstacle for brain tumor therapy. As a result, despite intense research efforts over the last decade, malignant gliomas remain one of the deadliest types of cancer. Our research teams at The Friedman Brain Institute are studying the molecular and cellular components that drive brain tumors, and developing novel strategies to deliver anti-cancer agents to the tumor site.
Molecular Characteristics of Glioma Stem Cells
Glioma stem cells have been described as tumor cells that behave like stem cells (self-renewal and multipotency), with enhanced resistance to chemotherapy and radiation compared to non-stem cells. The glioma stem cells are likely to be the source of cells from which a tumor regrows after therapy. We are pioneering new avenues of glioma research by defining subsets of glioma stem cells in mouse transplant studies with viral lineage markers, which will lead us to understand molecular programs that control renewal and survival of cancer stem cells. Armed with this knowledge, we plan to design novel clinical interventions that will improve outcomes for glioma patients.
Prognostic Genetic Factors for Success of Brain Tumor Therapy
The inherent genetic instability of cancer cells and their resulting adaptive abilities is a major reason why gliomas inevitably recur following treatment and are ultimately fatal. A greater understanding of the cancer genome as a dynamic, three-dimensional structure will lead to the development of new strategies to address cancer evolution directly. We also seek to understand how current standard treatment regimes, such as radiation therapy and chemotherapy, interact with the cancer genome to influence the way in which tumor cells change through time and diversify in different compartments in the brain.
Scientist involved: Raymund Young
Systems Pharmacology of Brain Tumor Chemotherapy
Our laboratory characterizes the pharmacokinetic and pharmacodynamic properties of anticancer drugs for brain tumors. These studies have a common goal of understanding the variables that influence drug disposition and dynamics in the tumor. Through the use of detailed measurements of drug concentrations, we build physiologically based models that provide mechanistic information and allow for model predictions to be made. The progression of preclinical studies may lead to new drug treatment strategies and means to optimize drug treatment regimens in patients.
Scientist involved: Thomas O'Loughlin
Glioma Therapy by Gene Delivery Through Stem Cells
We investigate new strategies for adjuvant treatment of malignant brain tumors. With support from the National Institutes of Health, private foundations and industry, we investigate promising new modalities and compounds to kill brain tumor cells. We put a special emphasis on embryonic stem cells, which are currently tested as gene delivery vehicles in animal models of brain tumors.
Scientist involved: Isabella Germano
Laboratory for Pediatric Brain Tumor Research
We use sophisticated mouse genetics approaches to model pediatric brain tumors including medulloblastoma and DIPG so that they are more reflective of their human disease counterparts. Our laboratory seeks to understand the biology of these brain cancer cells and their microenvironment at single cell resolution during tumor formation and following standard therapy to identify treatment resistance mechanisms. Our goal is to identify therapeutic vulnerabilities that can be genetically and pharmacologically assessed in our preclinical models prior to clinical trials in patients. We put an emphasis on novel nanotechnology-based approaches to enhance drug delivery across the blood-brain barrier to improve patient outcomes and reduce treatment-related toxicities.
Scientists involved: Praveen Raju