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Fascinating Mouse Study Hints We May One Day Have mRNA Vaccine for Skin Cancer

14 JANUARY 2022

Being sun smart could one day include a vaccination not unlike those currently providing millions around the world with immunity against coronavirus.

While most immunizations sensitize our immune system to an aggressive agent like a virus or even cancer cell, emerging mRNA vaccine technology could instead train our bodies into generating additional antioxidant proteins, boosting our ability to shield our DNA from damage caused by sunlight.

 

A recent study on genetically altered mice conducted by researchers from the US and Japan has confirmed the role of an antioxidant enzyme in guarding against the chemical trauma caused by sun exposure.

If the body could be encouraged to make more of the enzyme under the right circumstances, it's not out of the realm of possibility that one day, such an approach could give us one more layer of protection against skin cancer

So far the concept is largely speculative, with plenty of obstacles to overcome. But given the success of mRNA vaccines in responding to the current pandemic, it's an option Oregon State University pharmacologist Arup Indra thinks is rich with possibility.

"For more than 40 years researchers have looked at dietary antioxidants as a possible source of inexpensive, low-risk agents for cancer prevention but they have not always performed well in clinical trials and in some cases have actually been harmful – hence the need to try to intervene with new chemoprevention agents such as an mRNA vaccine," says Indra.

Antioxidants work by interfering with oxidation, a chemical process which results in the loss of a molecule's electrons. For delicate structures like our DNA, this deficit can lead to chemical changes that dramatically raise the risk of cancerous mutations.

 

High-energy radiation, including frequencies of light in the ultraviolet part of the Sun's spectrum, do a good job of knocking electrons free. Fortunately, we have specialized cells called melanocytes that can spin out umbrellas of tanning pigment to shield us from a portion of this radiation.

Ironically, this process of producing the pigment generates its own oxidative by-products, called reactive oxygen species. It's a balance our bodies work hard to keep in check, producing a range of biochemical systems that keep a lid on oxidation.

Thioredoxin reductase 1 (TR1, encoded by the TXNRD1 gene) is a prime example. Used by melanocytes to compensate for their release of reactive oxygen species, it activates another protein called thioredoxin, which among other things binds reactive oxygen species before they can damage more important structures.

The reductase enzyme has not only been observed at elevated levels in skin cells after UV exposure, but in other tissues affected by various cancers, including melanoma. This malignant cancer of the melanocyte is the deadliest of skin cancers, with more than 60,000 people losing their lives to the illness every year.

 

Finding a way to get on top of the oxidative damage early using some of the body's own protective enzymes just might cut that death toll.

First things first though. While TXNRD1 seems like a good candidate for enhancing sun protection, researchers needed to check their assumptions using a living model.

Removing the TXNRD1 gene in mice provided the research team with a way to study the enzyme's role in pigmentation and the ability of melanocytes to respond to oxidative stress resulting from exposure to ultraviolet-B radiation.

The results were promising, suggesting a clear potential in delivering TXNRD1 to skin cells to help promote melanin production and to limit the damage caused by sun exposure.

While it would take a lot more research to develop, messenger RNA encoding this enzyme could be delivered through the body through the kind of vaccine technology being implemented in SARS-CoV-2 vaccines produced by Pfizer and Moderna.

"People at increased risk of skin cancer, such as those who work outside in sunny climates, could ideally be vaccinated once a year," says Indra.

 

In spite of this super-early, promising groundwork, there are still a lot of reasons to treat the results with some caution.

Thioredoxin reductases perform a number of tasks in the body to do with cell growth. While they seem to play a role in some aspects of cancer prevention, TXNRD1 has also been found to contribute to the migration of cancer cells, including in breast and colorectal carcinomas. It also seems to play a role in the spread of melanomas themselves.

Knowing more about its precise activity in development and cell movement could help establish protocols for its safe use as a protective agent.

Optimism for TXNRD1's potential aside, the idea of using mRNA vaccines to combat oxidative stress is one researchers are taking seriously.

"Clearly we're at the tip of the iceberg but the possibilities are exciting for preventing different types of disease progression including cancer by modulating the bodies' antioxidant system," says Indra.

This research was published in the Journal of Investigative Dermatology.