Defective Tumor Suppressor Gene Replacement and Oncogene Inactivation for the Treatment of Cancer
Year: 2020
Type: book-chapter
Abstract: The strategy for inactivating or replacing cancer-causing genes is analogous to the classic concept of gene therapy for replacing defective or nonfunctioning genes. So far, this strategy has been applicable to two gene families implicated in carcinogenesis: dominant oncogenes and tumor suppressor genes. Previous studies have shown that regional administration of viral vectors expressing wild-type p53 protein and antisense Κ -ras RNA in orthotopic tumor models prevents the growth of tumors with the respective genetic lesions and mediates regression of large established tumors. These data provide the rationale for two novel clinical protocols recently approved by the NIH Recombinant DNA Advisory Committee and FDA: one of these will replace a defective p53 gene with a normal p53 encoded by a recombinant retrovirus injected intratumorally, and the other inactivate mutant Κ -ras mRNA via the expression of antisense Κ -ras RNA. If these methods are efficacious, their lack of toxicity may provide a sufficiently high therapeutic index to allow their use as adjuvants to surgery in patients with earlier stages of cancer or as agents to prevent second primary cancers in individuals with 280 genetically abnormal premalignant lesions. Although substantial research and development must be done, the possibility of specific gene targeting with a high therapeutic index makes gene activation or replacement a promising area for investigation.
Source: CRC Press eBooks
Author: Jack Roth
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W3045902287