Gene Therapy and Targeted Toxins for Glioma

CASTRO; CANDOLFI; KROEGER; KING; CURTIN; YAGIZ; MINEHARU; ASSI; WIBOWO; MUHAMMAD; FOULAD; PUNTEL; LOWENSTEIN

CURRENT GENE THERAPY

BENTHAM SCIENCE PUBL LTD

Lugar: Oak Park; Año: 2011 vol. 11 p. 155 - 180

1566-5232

The most common primary brain tumor in adults is glioblastoma. These tumors are highlyinvasive and aggressive with a mean survival time of nine to twelve months from diagnosis todeath. Current treatment modalities are unable to significantly prolong survival in patientsdiagnosed with glioblastoma. As such, glioma is an attractive target for developing noveltherapeutic approaches utilizing gene therapy. This review will examine the available preclinicalmodels for glioma including xenographs, syngeneic and genetic models. Several promisingtherapeutic targets are currently being pursued in pre-clinical investigations. These targets will bereviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses,tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapyparadigms aim to determine which strategies will provide rapid tumor regression and long-termprotection from recurrence. While a wide range of potential targets are being investigatedpreclinically, only the most efficacious are further transitioned into clinical trial paradigms.Clinical trials reported to date are summarized including results from conditionally cytotoxic,targeted toxins, oncolytic viruses and oncogene targeting approaches. Clinical trial results have notbeen as robust as preclinical models predicted; this could be due to the limitations of the GBMmodels employed. Once this is addressed, and we develop effective gene therapies in models thatbetter replicate the clinical scenario, gene therapy will provide a powerful approach to treat andmanage brain tumors.