Melanoma accounts for only 10 percent  of all skin cancers but is responsible for a staggering 80 percent of skin cancer-related deaths.

Melanoma is the result of uncontrollable growth of the pigment-producing skin cells in our body called melanocytes. Melanoma is also among the top 10 most common cancers in the United States. Known risk factors for melanoma are over exposure to sun, certain chemicals such as arsenic, alcohol, and people with lighter skin tone. Treatment varies depending on the stage of melanoma when diagnosed, ranging from surgery for early stages to more complex therapies for advanced cases, such as chemotherapy or immunotherapy. While early-stage melanoma has high survival rates, advanced cases are much harder to treat, with survival rates dropping as low as 30 percent.

Biomedical researchers world-wide have been working relentlessly to discover new treatments for cancer. To be successful, researchers need to understand exactly how each type of cancer works at the cellular and molecular level within our body. We are looking closely at how different types of cancer cells survive, grow, and move to different sites in the body. For example, it is known that chronic inflammation can promote the progression of specific cancers. Therefore, chronic inflammation is now recognized as a risk factor for cancer.

Our laboratory investigates lipid molecules called eicosanoids produced by white blood cells in our body. One subgroup of eicosanoids is called cysteinyl leukotrienes or Cys-LTs, that primarily promote inflammation. Cys-LTs are released by our white blood cells and bind to two specific receptors located on different cell surfaces, that we can call Cys-LT receptor 1 and Cys-LT receptor 2. These receptors work just like TV antennas because they receive signals from the bound Cys-LTs and transmit them to the inside of the cell which then causes the cell to undergo multiple cellular changes to induce inflammation along with other changes.

What is so important about Cys-LTs and their cell receptors? Primarily, they have been extensively studied for their roles in inducing asthma, which is an inflammation of the lungs. As a result, drugs that specifically block each of these Cys-LT receptors are well established. In fact, a receptor 1 blocker, montelukast, has been prescribed to asthmatic patients, with minimal side-effects, for over a decade under the brand name Singulair. In addition, Cys-LTs and their receptors have been under investigation by many researchers to better understand their role in cancer progression.

My research is focused on investigating the role of Cys-LTs and their receptors in the progression of melanoma. My long-term goal is to use these asthma drugs for the treatment of melanoma. By using already existing asthma drugs such as Singulair, we are eliminating the time required for the development of a new drug, as well as the harsh side-effects of a typical chemotherapeutic drug used to treat melanoma.

The initial results from my research confirmed that Cys-LTs were capable of promoting cancer cell survival, growth, and migration in cell cultures. When these cancer cells were given the blockers for both the Cys-LT receptors, the survival, growth, and migration of the cells decreased significantly.

I also discovered that the Cys-LT receptors were promoting cancer cell survival and growth by increasing the levels of a specific cellular protein which triggers cell survival and growth. We then tested these exciting cell culture results in a mouse model that has been modified by completely removing both Cys-LT receptors. Therefore, Cys-LTs cannot bind to the missing receptors to induce inflammation in this mouse model. We injected melanoma cells into this mouse model and indeed found that the tumors formed were much smaller in size compared to the tumors formed in a normal mouse model that expressed Cys-LT receptors. These results indicate that Cys-LT receptors can promote melanoma.

To test if we can use the Cys-LT receptor blockers, to treat melanoma, we first injected melanoma cells into a normal mouse model to develop tumors. Once the tumors developed, we treated the mouse model with the Cys-LT receptor blockers and monitored tumor growth. As expected, the tumors were significantly smaller in the normal mouse model that received the Cys-LT receptor blockers compared to the normal mouse model that did not receive any blockers.

What is exciting about our research results is that asthma drugs such as Singulair, could be used alongside existing cancer treatments, potentially making them more effective.

This approach, known as combination therapy, is like attacking cancer from multiple angles at once. By adding these asthma medications to the current arsenal of cancer treatments, doctors might be able to improve the overall survival for patients with melanoma. More investigation is ongoing in order to determine the right dosage, safety, and efficacy.

Emma Elizabeth Sabu Kattuman is a Ph.D. student in the molecular medicine track at the University of Toledo college of medicine and life sciences in the biomedical science program. She is doing her research in the laboratory of Dr. Sailaja Paruchuri in the department of physiology and pharmacology. For more information, contact EmmaElizabeth.SabuKattuman@rockets.utoledo.edu or visit utoledo.edu/med/grad.

First Published October 7, 2024, 1:27 p.m.