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.
Written by Karen Selby, RN • Edited By Walter Pacheco • Medically Reviewed By Dr. Andrea Wolf
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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.
- Sometimes when healthy cells are exposed to things like asbestos, it can cause damage to their DNA. This damage can make the cells start multiplying and reproducing too much, which leads to tumors.
- The p53 gene prevents this by activating proteins that arrest cell division and repair corrupted DNA.
- When the damage to our DNA cannot be fixed, the p53 gene will start a process called apoptosis. This process helps get rid of cancer cells before they can make more of themselves.
- 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.
Doctors are trying to figure out how to fix or replace damaged p53 genes in cancer cells. It could help treat different types of cancer. Many researchers believe the emerging science of gene therapy holds the key.
A gene therapy treatment on p53 could be safely combined with traditional cancer treatments. This may increase the overall effectiveness of the treatment plan.
Gene therapy is one of several new treatments that researchers are hoping will bring us closer to a cure for mesothelioma. Another form of gene therapy in development for mesothelioma includes suicide gene therapy.
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 tried different methods, but none of them has been given the green light from the FDA for mesothelioma treatment.
According to a 2021 research study, approximately 80% to 85% of mesothelioma patients bear the wild-type p53 gene.
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.
Back in 2003, Chinese scientists created a special gene therapy to help people with head and neck cancer. This treatment was called Gendicine and it got the okay from the Chinese State Food and Drug Administration. 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 uses changed viruses to attack cancer cells while leaving healthy ones alone. Experts have had some success using a type of measles virus to go after mesothelioma cells.
Scientists are trying to make the treatment more successful by adding p53 genes to oncolytic viruses, but they still need to check if it works.
Nanoparticles
Another group of researchers is making tiny particles to carry special genes into cancer cells. Known as synthetic nanoparticles, they could help deliver tumor-suppressor genes like p53.
Nanoparticles are like tiny viruses that can deliver medicine only to cancer cells. That means the healthy cells in your body remain unharmed. They likely won’t make you sick or cause a reaction from your immune system.
Reactivating p53 with Drugs
Scientists are working on a new type of cancer treatment that involves fixing mutated p53 genes. This medicine could be used to treat existing cancers. It might prevent formation by correcting any broken p53 genes before they have a chance to cause problems.
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