Brain Cancer Zebrafish Xenotransplant Model for Drug Screening

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DESCRIPTION (provided by applicant): Metastatic brain tumors occur in approximately 10-30% of adult cancers. Many forms of cancer can spread to the brain, the most common being lung cancer, breast cancer, melanoma, kidney cancer, bladder cancer, certain sarcomas, testicular and a number of others. The most commonly diagnosed primary malignant brain tumor of adults is glioblastoma multiforme (GBM). It represents about 30% of all primary brain tumors. The characteristic features of GBM are that they proliferate rapidly and invade adjacent tissue although rarely metastasize outside the brain. Complete surgical removal of GBM is not possible. The prognosis for survival of patients with glioblastoma remains at approximately 1 year, despite aggressive surgery, radio- and chemotherapy. The main obstacle to treatment of brain cancer is the blood brain barrier (BBS). Approximately 98% of all small-molecule drugs and nearly all large- molecule drugs cannot cross this barrier to effectively target brain cancer. In addition active efflux mechanisms exist in brain vessels to pump drugs out of the brain. There is no efficient in vivo model system for testing drug candidates for their ability to thwart the blood brain tumor barrier or the efficient drug efflux mechanisms that reduce the efficacy of chemotherapy for brain cancer. This SBIR aims to develop a zebrafish xenograft model for identifying potential drug candidates for brain cancer. This SBIR will assess embryogenesis, patterning, cancer cell proliferation, the ability of drugs to cross the BBB and their effects on brain tumors.