p53 Gene Therapy

The p53 tumor-suppressing gene typically repairs DNA that has become unstable and may be a target for gene therapy to treat mesothelioma.

The p53 gene is known as a suppressor gene and it is largely responsible for regulating cell growth so we don’t develop tumors. The problem is that genes can become damaged and can be difficult to replace and repair without intervention. 

Cells can become cancerous if they are damaged by outside forces. Things like asbestos, which is a leading cause of mesothelioma, and other carcinogens wreak havoc on cells and cause them to become unstable. The p53 tumor-suppressing gene goes to work to try and repair DNA that has become unstable. If the DNA cannot be repaired, p53 will essentially “destroy the evidence”, and try to get rid of the cancerous cell before it can corrupt others via reproduction. This gene also works to restrict blood flow to tumors in an attempt to inhibit their growth, as well as jumpstart immune cells to do their job and go to war against the cancerous cells. 

The problem can get out of hand if the p53 gene itself comes under attack. Think of it as the leader of guards that are surrounding and protecting a castle. The gene is supposed to cut down the corrupted DNA and tell other members of the guard, meaning other cells, where they should attack. If the leader is corrupted, there is no one to give the orders and the line of defense will fall. 

Research has shown that one of the ways to identify malignant mesothelioma in patients is with the mutation of p53 genes

If your p53 genes are corrupted, they will quickly mutate and allow cancerous cells to spread and divide more quickly and become stronger. With the cancer cells now having the p53 genes on their side, they will be more resistant to attack so doctors will have to get more creative. 

Currently, there isn’t any way to fix or restore p53 genes once they’ve become damaged or irreparable. If there were a way to do so, it would be groundbreaking as a way to combat aggressive cancers like mesothelioma that are difficult to treat or impossible to cure. Gene therapy seems to be the direction that scientists are leaning towards as the gateway to a cure for mesothelioma and related cancers.

If used as a combination treatment, the effectiveness would likely be very successful and heighten the survival rate for those with aggressive forms of cancer so researchers are looking at this as one potential area for development.

Possible Methods for Gene Therapy

It would be a major development to be able to take healthy p53 genes and bring them directly to cancerous cells but the problem is with the transfer. How do you get p53 genes safely delivered to the cells that need help?

There have been no surefire methods of delivery that cause any significant benefits to date. 

Medicinal

There are a number of experimental drugs aimed towards helping with cancer treatments and therapies. What this specific solution would aim to do is repair or simply “stitch-up” the damaged p53 genes so that they function properly and can go about their normal business.

If this were to be successful, it would revolutionize cancer treatment, and even possibly branch into the territory of being a cancer preventative. 

Viruses

Both methods of engineering and modifying viruses to transmit healthy p53 genes into cancerous cells are promising, but they need more development to show effectiveness as beneficial treatments.

The method of removing the sickly viral DNA from a virus to inject them directly into cancerous tumors could be a direct form of treatment. Unfortunately, nothing conclusive has happened with this method as the virus has either been unable to reach the cells completely, or they are killed off by immune cells before they are able to do so. The p53 genes die out with the viral DNA so it cannot be delivered. 

Oncolytic viruses, which is the method of injecting viruses directly into cancerous cells to attack them instead of normal cells, have demonstrated mild success. More research needs to be done to determine the reliability and viability of this method. If they were to add p53 genes to these viruses before injection, it may increase the chances of success. The issue here is still the risk of infection and the manner through which the p53 genes will be transmitted along with the virus. 

Nanoparticles

Because the problem is with the delivery of p53 cells from point A to point B, many researchers have focused their attention on transmitters. If a nanoparticle could do the job of carrier and transmit healthy p53 genes or other forms of treatment directly to cancerous cells, it would certainly be a more viable method of transfer.

They would not put the patient at risk of infection and would hopefully not be killed off my immune cells in transit. 

Think of these particles somewhat like the Trojan Horse. If they can get the package of p53 delivered to the enemy cells without detection from the immune cells, there will be a greater success as the p53 cells will be able to slip in and attack the cancerous cells stealthily. 

What Else?

Though all of these methods are still in stages of development, it is promising that there are several options in the works to get us closer to finding a proper treatment for mesothelioma. With such an aggressive form of cancer, it can be difficult to treat and most methods only a partial job. With the success of p53 delivery directly to cancerous cells, it could revolutionize cancer treatments and cut down on invasive and painful procedures like surgery, chemotherapy, and radiation. 
It has been described through extensive research that antibodies are typically reactive to p53 proteins.

This shows a potential pathway towards future gene therapies that will change the way we treat cancers like mesothelioma.

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