Genetic surgery - a right strategy to attack cancer.
The approaches now united under the term "gene therapy" can be divided into two broad strategies: (1) strategy using the ideology of molecular targeted therapy, but with genes in the role of agents targeted at certain molecular component(s) or pathways presumably crucial for cancer maintenance; (ii) strategy aimed at the destruction of tumors as a whole exploiting the features shared by all cancers, for example relatively fast mitotic cell division. While the first strategy is "true" gene therapy, the second one, as e.g. suicide gene therapy, is more like genetic surgery, when a surgeon just cuts off a tumor being not interested in subtle genetic mechanisms of cancer emergence and progression. This approach inherits the ideology of chemotherapy but escapes its severe toxic effects due to intracellular formation of toxic agents. Genetic surgery seems to be the most appropriate approach to combat cancer, and its simplicity is paradoxically adequate to the super-complexity of tumors. The review consists of three parts: (i) analysis of the reasons of tumor supercomplexity and fatally inevitable failure of molecular targeted therapy, (ii) general principles of the genetic surgery strategy, and (iii) examples of genetic surgery approaches with analysis of their drawbacks and the ways for their improvement.
Institute of Molecular Genetics, Shemyakin-Ovchinnikov, Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia. edsverd@gmail.com
Eugene D
ED
Sverdlov
D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D050130:Oncolytic Virotherapy / Q000379:methods; D011355:Prodrugs / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D017154:Stromal Cells; D059016:Tumor Microenvironment; D014779:Virus Replication / Q000235:genetics
D011355:Prodrugs