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Defining Gene Functions in Tumorigenesis by Ex vivo Ablation of Floxed Alleles in Malignant Peripheral Nerve Sheath Tumor Cells
Published on: August 25, 2021
Ionizing radiation: a genetic switch for cancer therapy
J J Mezhir1, K D Smith, M C Posner
1Department of Surgery, The University of Chicago Hospitals, IL 60637, USA.
Cancer Gene Therapy
|August 6, 2005
Summary
Radiation-targeted gene therapy uses radiation-inducible promoters to activate cancer-killing transgenes. TNFerade, an adenoviral vector, delivers tumor necrosis factor-alpha to solid tumors, localized by X-rays.
Area of Science:
- Oncology
- Gene Therapy
- Radiation Oncology
Background:
- Gene therapy for cancer is promising yet challenging.
- Radiation-inducible genes enable targeted gene therapy approaches.
- Promoters of radiation-inducible genes control transgene expression post-irradiation.
Purpose of the Study:
- To review the development of radiation-targeted gene therapy.
- To discuss TNFerade, an adenoviral vector utilizing radiation-inducible elements.
- To summarize preclinical and clinical data for TNFerade in solid tumors.
Main Methods:
- Utilizing radiation-inducible promoter elements (early growth response-1) to drive transgene expression.
- Delivering transgenes encoding cytotoxic proteins (human tumor necrosis factor-alpha) via adenoviral vectors.
- Localizing tumoricidal effects temporally and spatially using X-rays.
Main Results:
- Conceptual development of TNFerade, an adenoviral vector.
- Preclinical studies demonstrating efficacy and safety.
- Clinical trials investigating TNFerade for various solid tumors.
Conclusions:
- Radiation-targeted gene therapy offers localized cancer treatment.
- TNFerade represents a novel approach combining gene therapy and radiation.
- Further clinical evaluation is ongoing for diverse solid tumors.
Related Concept Videos
Mutations
Overview
Cancer
Cancers arise due to mutations in genes involved in the regulation of cell division, which leads to unrestricted cell proliferation. Modern science and medicine have made great strides in the understanding and treatment of cancer, including eradicating cancer in some patients. However, there is still no cure for cancer. This is largely due to the fact that cancer is a large group of many diseases.
Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
Targeted Cancer Therapies
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against specific...
There are several types of targeted therapies against specific...
Mutations
Mutations are changes in the sequence of DNA. These changes can occur spontaneously or they can be induced by exposure to environmental factors. Mutations can be characterized in a number of different ways: whether and how they alter the amino acid sequence of the protein, whether they occur over a small or large area of DNA, and whether they occur in somatic cells or germline cells.
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Chromosomal Alterations Are Large-Scale Mutations
While point mutations are changes in a single nucleotide in...
Cancer-Critical Genes I: Proto-oncogenes
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...

