Enzyme Discovered That Could Enable an mRNA Vaccine to Prevent Skin Cancer

Skin cancers are the most common cancer in the United States and in countries with intense sunlight. Most skin cancers are diagnosed at an early stage and are easy to manage and treat. However, about 3–5% of skin cancers are melanoma, an aggressive type whose treatment differs from that of other skin cancers. Until the discovery of immunotherapies and targeted drugs directed at BRAF mutations, we had no effective treatment option for melanoma – a development of the last 10 years. Despite treatment advances, melanoma still causes most skin cancer-related deaths. Turkish Cancer Statistics report that 1756 melanoma diagnoses and 888 deaths from this disease occurred in Turkey in 2020. There is therefore intensive work on strategies to “prevent” melanoma.

Melanoma occurs in melanocytes, the cells that produce melanin, the pigment determining skin color. Ultraviolet radiation from sunlight creates oxidative stress, causing DNA damage. As this damage accumulates, cells multiply uncontrollably and become cancerous.

In January 2022, Journal of Investigative Dermatology published a study reporting that the TR1 protein could be produced through an mRNA vaccine, which could prevent skin cells from becoming cancerous. As is known, mRNA vaccines produced against COVID-19 by companies such as BioNTech and Moderna are being used successfully against coronavirus and have saved many lives during the pandemic.

The study focused on an enzyme called TR1 (Thioredoxin Reductase 1). This enzyme plays the most critical role in the antioxidant systems of melanocytes, the skin cells. Antioxidants protect against reactive oxygen species that damage cellular DNA. The TR1 enzyme protects cells from these harmful molecules and prevents them from becoming cancerous. Following this discovery, the researchers stated that increasing the TR1 protein might be possible with mRNA vaccines.

Melanocytes, which produce the melanin that gives skin its color, are constantly exposed to internal and external reactive biochemicals, but intracellular antioxidants and other regulators are finely tuned to suppress this cellular stress. This control is disrupted during melanoma formation, and TR1 has a critical role here.

The figure below: Melanocytes are naturally exposed to multiple sources of oxidative stress:

Messenger RNA (mRNA) vaccines work by directing cells to produce specific proteins. In this case, an mRNA vaccine that induces TR1 production could provide protection against melanoma. The TR1 enzymes produced after vaccination could prevent cell damage and thereby prevent melanoma development.

What Does This Study Mean for Us?

• This study is still at the preclinical (before human trials) stage.
• According to the researchers, a vaccine developed solely for TR1 may be sufficient to prevent skin cancer. This is because oxidative stress and DNA damage were observed in cells lacking the TR1 enzyme despite the presence of other antioxidants.
• Preventive mRNA vaccines against skin cancer may be ready for use in the near future. The aim is to protect people at high risk of melanoma, such as those with a family history of melanoma, many moles or a previous melanoma, by vaccinating them at regular intervals.