Gene therapy of cancer through restoration of tumor-suppressor functions?
The tools and concepts of gene therapy are being applied to the development of effective new treatments for human cancer. Most human cancers are associated with multiple interacting and cooperating mutations in protooncogenes and tumor suppressor genes. In several model systems, some features of the tumor phenotype can be suppressed in vitro through the restoration of expression of tumor suppressor genes such as Rb and p53. Before this phenomenon can serve as the basis for gene therapy of cancer, many conceptual and technical problems must be solved. Because such genetically modified cells continue to contain and express other mutations, it is important to determine the mechanisms and frequency of reversion to the tumor phenotype. To be clinically useful, highly efficient and targeted gene delivery vectors must be developed. The experimental evidence for tumor suppression by restored gene expression and the pivotal role played by tumor suppressor genes in the regulation of cell replication suggests that restored expression of some tumor suppressor genes in some tumor cells will eventually play a role in cancer gene therapy.
Friedmann
T
T
Center for Molecular Genetics, School of Medicine, University of California, San Diego, La Jolla 92093.
D000818:Animals; D016147:Genes, Tumor Suppressor / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating / Q000378:metabolism; D008222:Lymphokines / Q000235:genetics; D008954:Models, Biological; D009154:Mutation; D009369:Neoplasms / Q000235:genetics / Q000628:therapy*; D010641:Phenotype; D011519:Proto-Oncogenes / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D008222:Lymphokines; D014409:Tumor Necrosis Factor-alpha