Medulloblastoma Treatment using Gene Therapy

Usually initiated in cerebellum and the fourth ventricle and caused by the secondary increased intracranial pressure due to blockage of the fourth ventricle, medulloblastoma (MB) is the most common malignant brain tumor in children. Traditionally, surgical therapy is predominantly conducted with maximal resection of the tumor and followed by radiation or chemotherapy according to its philological subtypes. However, due to the fact that the traditional treatments result in unsatisfactory peripheral prognosis and the final death from relapse to most of the patients, increasing efforts have been made in the field of gene therapy to improve the prognosis. So far, four of gene therapy strategies have been tested in cells or animal xenograft models including 1) oncolytic virotherapy using adenovirus, reovirus, myxoma virus, and measles virus; 2) suicide gene therapy, focusing on HSV-tk with GCV system and rCE with CPT-11 system; 3) radiation sensitivity enhancement by down regulation of MMP-9, uPAR, SPARC, CDK6 or elevation of NIS; and 4) miRNA-based gene therapy. To date, gene therapy to MB has been proven to be promising at the level of cells lines and xenograft mouse models although no clinical trials have been conducted. In this paper, we review the relevant gene therapy strategies for the MB treatments and discuss the pertinent challenges, further refinement and future directions in this field.