Brain Tumor Research at Dana-Farber Cancer Institute

 Introduction

 Although primary brain tumors are relatively uncommon, it affects over 50,000 people each year in the United States . Almost half of these tumors are malignant gliomas and currently incurable. 

 Investigators at Dana-Farber aim to discover a new generation of targeted drugs to attack specific mutated proteins that are found in brain tumor cells.  The goal of these “smart” drugs is to kill only tumor cells, and spare normal cells. Malignant gliomas however present a unique challenge in that mutations in at least a half dozen different genes are currently known to contribute to their growth. This genetic diversity require a personalized approach – a system for individualized diagnosis and treatment. 

 1) Optimizing Existing Therapies: Thanks to a flurry of activity in the pharmaceutical industry, there are drugs currently “in the pipeline” that target most of the known genetic mutations in brain tumors. However, these drugs, almost without exception, were developed for the more common solid tumors of adults (e.g. breast, lung or prostate).  Brain cancers present a challenge unique to cancer medicine – namely the blood/brain barrier.  Many cancer medicines that are effective on other tumors fail on primary cancers of the brain because they are unable to penetrate into the brain.  A major effort is underway to identify the subset of drugs developed for other tumors that might prove effective on brain cancers. 

 2) Anti-Angiogenic Therapies: Dana-Farber investigators have made notable contributions to the clinical trials of drugs that prevent the tumor from making new blood vessels (anti-angiogenic therapy). These studies led to FDA approval of Avastin for recurrent glioblastomas in 2009. However, not all patients respond to avastin, and patients who respond almost always recur. A major goal of research at Dana-Farber is to understand the molecular predictors of responsiveness to Avastin so that only those patients who will benefit will receive the treatment, and those who will not benefit will be spared unnecessary side effects. In addition, we are trying to study the molecular mechanisms that result in tumors eventually becoming resistant to these anti-angiogenic drugs in the hopes of overcoming these mechanisms and improving outcome.

3) New Drug Development: The most common signaling pathway to be disrupted in brain cancer is called the P13K pathway.  There is a major effort underway to develop drugs that block PI3 kinase, as well as other important molecular targets, in brain tumors

 4) Glioblastoma Stem Cells: Based on work at Dana-Farber and other centers, there is compelling evidence that glioblastomas arise from tumor stem cells. Investigators at Dana-Farber have identified a critical gene that is required for tumor stem cells to grow called Olig2. There is now a major effect to find drugs to block Olig 2 and stop stem cells from growing, providing hope that these tumors can finally be completely eradicated.

5) Personalized Trials and Therapies: Because brain cancers have multiple genetic changes, a molecular drug that blocks a specific target may only be helpful in a subset of patients. We are now trying to study the major genetic changes in all patients coming to Dana-Farber with brain cancer so that we can match the most appropriate drugs to their tumors.