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Updated: Dec 25, 2025
Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Not gene therapy, but genetic surgery-the right strategy to attack cancer
1Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry RAN, Moscow, Russia.
Abstract:
In this review, I will suggest to divide all the approaches united now under common term "gene therapy" into two broad strategies of which the first one uses the methodology of targeted therapy with all its characteristics, but with genes in the role of agents targeted at a certain molecular component(s) presumably crucial for cancer maintenance. In contrast, the techniques of the other strategy are aimed at the destruction of tumors as a whole using the features shared by all cancers, for example relatively fast mitotic cell division or active angiogenesis. While the first strategy is "true" gene therapy, the second one is more like genetic surgery when a surgeon just cuts off a tumor with his scalpel and has no interest in knowing delicate mechanisms of cancer emergence and progression. I will try to substantiate the idea that the last strategy is the only right one, and its simplicity is paradoxically adequate to the super-complexity of tumors that originates from general complexity of cell regulation, strongly disturbed in tumor cells, and especially from the complexity of tumors as evolving cell populations, affecting also their ecological niche formed by neighboring normal cells and tissues. An analysis of the most widely used for such a "surgery" suicide gene/prodrug combinations will be presented in some more details.
Insights
This review proposes dividing gene therapy into targeted gene therapy and genetic surgery. Genetic surgery, targeting shared cancer traits like rapid cell division, is presented as the more effective strategy for complex, evolving tumors.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Gene therapy encompasses diverse approaches for cancer treatment.
- Current methods are often categorized under a single
- gene therapy
- umbrella, potentially obscuring strategic differences.
Purpose of the Study:
- To propose a division of gene therapy into two distinct strategies: targeted therapy and genetic surgery.
- To argue for the superiority of genetic surgery in treating complex, evolving tumors.
- To analyze suicide gene/prodrug combinations used in genetic surgery.
Main Methods:
- Conceptual review and strategic analysis of gene therapy approaches.
- Examination of tumor characteristics, including cell division and angiogenesis.
- Detailed analysis of suicide gene/prodrug systems.
Main Results:
- Gene therapy can be broadly classified into targeted therapy (gene-based targeted agents) and genetic surgery (whole-tumor destruction).
- Genetic surgery, by exploiting universal cancer features, offers a simpler yet more adequate approach to complex tumors.
- Suicide gene/prodrug combinations are a key component of the genetic surgery strategy.
Conclusions:
- Genetic surgery represents a more pragmatic and effective strategy for combating complex, evolving tumors.
- The complexity of tumors as evolving cell populations necessitates approaches that target shared, fundamental characteristics.
- Further investigation into suicide gene/prodrug systems is warranted for optimizing genetic surgery outcomes.
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