Mesothelioma Gene Therapy

Genes are the blueprints for cell design in our bodies. Since DNA and RNA have been identified much has been learned about the functions of genes and how they can be altered. Scientists have also learned that gene mutation can be caused by a number of environmental factors. Faulty genes can deliver faulty instructions to growing cells, leading to mutations that can seriously affect health. Smoking, overexposure to the sun, exposure to toxic chemicals and substances can all cause damage to DNA that result in faulty genetic behavior.

In the case of mesothelioma, exposure to asbestos is the environmental factor that leads to development of this lethal cancer. There can also be a natural genetic predisposition to mesothelioma cancer however, and smoking has proven to be an additional aggravating factor for the disease. There is a group of rural villages in Turkey where an astonishing 50% of deaths are due to mesothelioma, a situation where genetics is clearly an issue. Malignant mesothelioma can have multiple types of gene damage contributing to its development and complicating attempts to develop genetic science that will help control or cure the disease.

Approaches to Mesothelioma Gene Therapy

Anti-angiogenesis medication is one promising form of gene therapy. This treatment involves introducing genes into the body that inhibit the development of blood vessels feeding the tumor, thus "starving" the cancer and either slowing its growth or killing it. One researcher refers to this approach as a "genetic tourniquet."

One of the characteristics of cancer cells is that they grow rapidly and reproduce by dividing. Gene therapy research has targeted this function by trying to develop a gene that in effect 'replaces' the faulty gene allowing this growth in cancerous cells, thus slowing or halting the growth of tumors.
A third approach has been the development of genes that are introduced into the body as replacements for genes in cancer cells. The altered cells are then rendered susceptible to certain types of anti-cancer medication, the defense mechanisms for those cells rendered useless. This approach creates so-called "suicide cells" that expose themselves to eradication.

The use of gene therapy for mesothelioma is still a subject for research rather than established treatment procedures. The theory of gene therapy seems to align itself well with cancer treatment, however the fact that mesothelioma cancer is a "multifactorial" disease with several contributing factors along with asbestos requires a multi-faceted approach to mesothelioma treatment. Gene therapy may prove to be most effective when utilized in conjunction with chemotherapy and radiotherapy, providing an attack on the cancerous tissue with several approaches.

One research project in France obtained good results in experiments with lab animals. These tests utilized several gene alteration protocols, some of which showed tangible results. Project scientists reported shrinkage in mesothelioma tumors; they noted as well that the combination of two types of gene therapy obtained excellent results while the use of just a suicide cell approach did not.

Current Status of Gene Therapy

The FDA's Center for Biologics Evaluation and Research (CBER) is charged with oversight on all gene therapy research conducted in the United States. There are numerous products developed by drug research companies for use in gene therapy that have been submitted for review. None have proceeded to the clinical trial stage yet. There have been setbacks in the early trials, including two deaths of participants whose immune systems were overwhelmed by the viral vectors used to introduce the therapeutic genes into the body. To date there are no clinical trials for gene therapy that have advanced to the Stage III point.

Sources:

  1. Genetic Predisposition to Fiber Carcinogenesis...American Association for Cancer Research, Dogan et al, 2006, http://www.medicalgeology.org/PDF/Dogan-CR5063.pdf
  2. Gene Therapy Strategies for Tumor Antiangiogenesis, Journal of the National Cancer Institute, Hwai-Loong Kong et al, February 1998, http://jnci.oxfordjournals.org/cgi/reprint/90/4/273.pdf
  3. Susceptibility of Mesothelioma Cells…to Suicide Gene Therapy, PubMed, National Institutes of Health, http://www.ncbi.nlm.nih.gov/pubmed/15474666
  4. Combined Suicide & Cytokine Gene Therapy for Peritoneal Carcinomatosis, Gut, Lechanteur et al, September 2000, http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1728025/pdf/v047p00343.pdf
  5. Gene Therapy, Human Genome Project, http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml#status

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