title: Gene therapy and targeted toxins for glioma.
abstract: The most common primary brain tumor in adults is glioblastoma. These tumors are highly invasive and aggressive with a mean survival time of 15-18 months from diagnosis to death. Current treatment modalities are unable to significantly prolong survival in patients diagnosed with glioblastoma. As such, glioma is an attractive target for developing novel therapeutic approaches utilizing gene therapy. This review will examine the available preclinical models for glioma including xenographs, syngeneic and genetic models. Several promising therapeutic targets are currently being pursued in pre-clinical investigations. These targets will be reviewed by mechanism of action, i.e., conditional cytotoxic, targeted toxins, oncolytic viruses, tumor suppressors/oncogenes, and immune stimulatory approaches. Preclinical gene therapy paradigms aim to determine which strategies will provide rapid tumor regression and long-term protection from recurrence. While a wide range of potential targets are being investigated preclinically, 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 not been as robust as preclinical models predicted; this could be due to the limitations of the GBM models employed. Once this is addressed, and we develop effective gene therapies in models that better replicate the clinical scenario, gene therapy will provide a powerful approach to treat and manage brain tumors.
authors: Gene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. mariagcastro2010@gmail.com
authors: Maria G
authors: MG
authors: Castro
authors: Marianela
authors: M
authors: Candolfi
authors: Kurt
authors: K
authors: Kroeger
authors: Gwendalyn D
authors: GD
authors: King
authors: James F
authors: JF
authors: Curtin
authors: Kader
authors: K
authors: Yagiz
authors: Yohei
authors: Y
authors: Mineharu
authors: Hikmat
authors: H
authors: Assi
authors: Mia
authors: M
authors: Wibowo
authors: A K M
authors: AK
authors: Ghulam Muhammad
authors: David
authors: D
authors: Foulad
authors: Mariana
authors: M
authors: Puntel
authors: Pedro R
authors: PR
authors: Lowenstein
mesh_terms: D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D003131:Combined Modality Therapy; D018390:Gene Targeting; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D007167:Immunotherapy; D007372:Interferons / Q000627:therapeutic use; D007378:Interleukins / Q000627:therapeutic use; D008954:Models, Biological; D014118:Toxins, Biological / Q000627:therapeutic use*
chemical_list: D007378:Interleukins; D014118:Toxins, Biological; D007372:Interferons