Gene therapy for human cancer: an essay for clinicians.
In the last decade our understanding of the processes that govern growth and differentiation has become quite sophisticated. A variety of tumor suppressor genes and more than 100 oncogenes have been identified. The roles of developmental genes in shaping the expression of neoplasia and of defective housekeeping genes in allowing mutations to persist and be transcribed have been appreciated. These advances have revolutionized our ability to diagnose and to formulate prognoses for patients with cancer. However, successful gene therapy for cancer has been elusive. This review highlights the current approaches to gene therapy for cancer and their scientific bases. The requirement that the therapy repair or destroy every cancer cell seems an insurmountable hurdle. Environmental manipulation through systemic administration of exogenous antisense may circumvent this problem in cases where it is appropriate. The more practical application of the technology of genetic engineering to facilitate cancer chemotherapy and immunotherapy is also reviewed. Particularly encouraging are the preclinical and clinical results of in vivo, in situ gene transfer. It remains to be determined if this local approach impacts favorably on survival.
Mastrangelo
M J
MJ
Department of Medicine, Jefferson Medical College, Philadelphia, Pennsylvania, USA.
Berd
D
D
Nathan
F E
FE
Lattime
E C
EC
D018014:Gene Transfer Techniques; D016153:Genes, Suppressor; D005818:Genetic Engineering; D015316:Genetic Therapy; D006801:Humans; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D009857:Oncogenes