Gene therapy for gliomas: molecular targets, adenoviral vectors, and oncolytic adenoviruses.
Currently, most of the approved clinical gene therapy protocols involve cancer patients and several of the therapies are designed to treat brain tumors. Two factors promoting the use of gene therapy for gliomas are the failure and toxicity of conventional therapies and the identification of the genetic abnormalities that contribute to the malignancy of gliomas. During the malignant progression of astrocitic tumors several tumor suppressor genes are inactivated, and numerous growth factors and oncogenes are overexpressed progressively. Thus, theoretically, brain tumors could be treated by targeting their fundamental molecular defects, provided the gene-drug can be delivered to a sufficient number of malignant cells. However, gene therapy strategies have not been abundantly successful clinically, in part because the delivery systems are still imperfect. In the first part of this brief review we will discuss the most common targets for gene therapy in brain tumors. In the second part, we will review the evolution of adenoviruses as gene vehicles. In addition, we will examine the role of recombinant mutant oncolytic adenoviruses as anticancer tools. From the results to date it is clear that gene therapy strategies for brain tumors are quite promising but more critical research is required, mainly in the vector field, if the strategies are to achieve their true potential in ameliorating patients with gliomas.
Alemany
R
R
Department of Neuro-Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Gomez-Manzano
C
C
Balagué
C
C
Yung
W K
WK
Curiel
D T
DT
Kyritsis
A P
AP
Fueyo
J
J
D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology; D014408:Biomarkers, Tumor / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000628:therapy*; D002986:Clinical Trials as Topic; D016147:Genes, Tumor Suppressor; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D005909:Glioblastoma / Q000235:genetics / Q000628:therapy; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006378:Helper Viruses / Q000235:genetics; D006801:Humans; D013577:Syndrome; D014779:Virus Replication
D014408:Biomarkers, Tumor