p53 Gene Therapy

Across all types of cancer, the most common genetic mutation doctors have observed involves the p53 tumor-suppressor gene. Many experimental gene-therapy approaches are based on repairing or replacing defective p53 genes.

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This page features: 11 cited research articles

In human DNA, certain genes are responsible for preventing cells from becoming cancerous. The p53 gene is one of the most important of these tumor-suppressor genes.

  • Healthy cells can become cancerous when carcinogens, such as asbestos, damage their DNA and cause them to start dividing and reproducing uncontrollably.
  • The p53 gene prevents this by activating proteins that arrest cell division and repair corrupted DNA.
  • In cases where the DNA damage is irreparable, the p53 gene initiates a process called apoptosis that destroys the cancer cell before it reproduces itself.
  • The p53 gene can also limit blood flow to tumors, which prevents growth and alerts nearby immune cells to attack cancer cells.

When the p53 gene itself is corrupted, however, cells lose a natural safeguard against becoming cancerous. Doctors have observed that more than half of human cancer cases involve mutated p53 genes. Improperly functioning p53 genes allow cancer to spread faster and become more resistant to treatment.

If doctors find an effective way to repair or replace mutated p53 genes in cancer cells, it could lead to a radical improvement in the treatment of many types of cancer, including mesothelioma and other asbestos-related cancers. Many researchers believe the emerging science of gene therapy holds the key.

A gene therapy treatment based on restoring p53 could be safely combined with traditional cancer treatments such as surgery, chemotherapy or radiation therapy to increase the overall effectiveness of the treatment plan.

Vectors for p53 Gene Therapy

The great challenge of gene therapy is to find a reliable way to deliver the tumor-suppressor gene to the cells that need it. Researchers have tested a few different DNA-delivery vehicles, or vectors, on several types of cancer, but so far, none of these gene-therapy techniques has been approved by the FDA for mesothelioma treatment.

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Nonreplicating Viruses

Many researchers have tried using genetically engineered viruses to deliver p53 genes to cancer cells. Researchers first remove the dangerous viral DNA from the viruses to ensure they cannot cause an infection in the patient. Then the researchers inject the altered viruses directly into the tumors.

This approach has proven safe, with very mild side effects, but it is currently inefficient for transmitting genes to cancer cells. The harmless viruses may not reach all the cancer cells in the tumor, or the body’s immune system may hunt them down before they can deliver the p53 genes.

In 2003, the Chinese State Food and Drug Administration approved a p53 gene therapy treatment for head and neck cancer called Gendicine. The American version of the treatment, Advexin, was submitted to the FDA in 2008, but it was not approved.

Oncolytic Viruses

Some researchers are trying to combine gene therapy with virotherapy. Virotherapy involves modifying viruses to infect and kill cancer cells while leaving healthy cells unharmed. Specialists have had some limited success using a modified form of the measles virus to target mesothelioma cells.

Researchers hope adding p53 genes to oncolytic viruses will make the treatment more effective than gene therapy or virotherapy alone, but the technology still needs to be tested.

Nanoparticles

Rather than modifying viruses, another group of researchers is designing artificial vectors to carry genes to cancer cells. Synthetic nanoparticles could carry tumor-suppressor genes such as p53, or they could carry targeted chemotherapy drugs.

Like viruses, nanoparticles could be designed to deliver their contents to cancer cells specifically, leaving healthy cells unaffected. In theory, however, nanoparticles would also be safer than viruses, creating no risk of infection, and they could travel through the body without provoking a response from the immune system.

Reactivating p53 with Drugs

Another experimental cancer therapy in development involves “patching” mutated p53 genes in cells so they can function normally again. Doctors could potentially use this medicine to treat cancer and prevent it by repairing defective p53 genes before cells have the chance to become cancerous.

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Karen Selby joined Asbestos.com in 2009. She is a registered nurse with a background in oncology and thoracic surgery and was the director of a tissue bank before becoming a Patient Advocate at The Mesothelioma Center. Karen has assisted surgeons with thoracic surgeries such as lung resections, lung transplants, pneumonectomies, pleurectomies and wedge resections. She is also a member of the Academy of Oncology Nurse & Patient Navigators.

Last Modified April 18, 2018
Sources
  1. Bressy, C., Hastie, E., and Grdzelishvili, V. (2017, April 6). Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy. Retrieved from http://www.cell.com/molecular-therapy-family/oncolytics/fulltext/S2372-7705(17)30009-8
  2. Xiao, J., et al. (2017, March 24). Efficacy of recombinant human adenovirus-p53 combined with chemotherapy for locally advanced cervical cancer: A clinical trial. Retrieved from https://www.spandidos-publications.com/ol/13/5/3676?text=fulltext
  3. Service, R. (2016, October 5). This protein is mutated in half of all cancers. New drugs aim to fix it before it’s too late. Retrieved from http://www.sciencemag.org/news/2016/10/protein-mutated-half-all-cancers-new-drugs-aim-fix-it-it-s-too-late
  4. Parrales, A., and Iwakuma, T. (2015). Targeting Oncogenic Mutant p53 for Cancer Therapy. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4685147/
  5. Dizaj, S., Jafari, S., and Khosroushahi, A. (2014). A sight on the current nanoparticle-based gene delivery vectors. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4046008/
  6. Tada, Y. et al. (2013). A Potential Therapeutic Strategy for Malignant Mesothelioma with Gene Medicine. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3581274/
  7. Business Wire. (2008, September 2). Introgen Receives Notice ADVEXIN U.S. BLA Not Sufficiently Complete to File. Retrieved from http://www.businesswire.com/news/home/20080902005490/en/Introgen-Receives-Notice-ADVEXIN-U.S.-BLA-Sufficiently
  8. Ma, G. et al. (2008). Gene medicine for cancer treatment: Commercially available medicine and accumulated clinical data in China. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2761194/

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