Co-local Delivery of Chemotherapeutics and Parp-inhibitors (Glioma Sensitizers) to Treat Glioblastoma Multiforme

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Glioblastoma (GBM) is one of the most aggressive and treatment-resistant of all human cancers. The median survival for these patients remains only 9–15 months from the time of diagnosis. A major limitation to effective treatment for GBM is the inability of treatments to cross the blood-brain/blood-tumor barrier, and the presence of drug efflux pumps, which prevent adequate concentrations of drugs to be achieved at the tumor. Many potential treatments fail due to i) their inability to target cancer cells that have invaded deep into normal brain tissue; ii) their inability to achieve drug concentrations required to kill cancer cells in the brain; or iii) limited toxicity of existing chemotherapy drugs against resistant glioma cells.

To overcome these major limitations, Jeffrey Karp, MD, and. Lata Menon, MD, will work together to use a new treatment approach that includes delivering tumor cell sensitizers and chemotherapy drugs at the same time. They aim to develop a new approach that will serve as a paradigm shift in the treatment of the GBM. This collaborative project takes advantage of the capability and resources at Harvard Medical School, Brigham and Women’s Hospital, and Massachusetts Institute of Technology.

Recently, Dr. Karp’s lab team has designed a new way to synthesize drug-based gels that can easily be injected into cancer cells and can accommodate high drug concentrations that will ensure that every molecule in the gel contains drug. The drug-based gels can accommodate multiple drugs for combination therapy, can be designed to remain stable for months in healthy brain tissue, and can be delivered in the event of tumor growth or recurrence.

Dr Menon will study the fate, delivery, and the treatment efficacy of the drug based gel in subcutaneous and orthotopic models of human glioma. This research will help prove how this gel works in animal models, so that this approach can be used to treat aggressive brain tumors.