Metastatic melanoma remains a significant cause of death in the United States, with average survival rates below 35% just 5 years after initial diagnosis. In order to improve outcomes for patients, a growing area of research has been to focus on patient-specific biomarkers, which may enable targeted therapy or contribute to prognostic tests to determine which therapy is best for a certain patient. One important existing prognostic factor in melanoma is the sentinel lymph node biopsy (SLNB), which takes a sample of patient lymph node (LN) tissue to determine the stage of a patients’ cancer. Unfortunately, there is limited knowledge on if there are specific biomarkers present in patient LN tissue from SLNB to predict efficacy for specific melanoma treatments. This is important because recent experiments have shown that patient LN tissue is critical in mediating immune cell interactions which contribute to responses in immunotherapy treatment. These experiments suggest that there may be biomarkers present in patient LN tissue. In this study, we seek to profile patient LN tissue to determine specific biomarkers associated with response to immunotherapy in both local and metastatic melanoma. We will utilize advanced gene sequencing and imaging technology with machine learning models to determine specific immune pathways and spatial architecture of immune cells in LN tissue. This research is critical because it will definitively establish pathways and biomarkers which predict responses to immunotherapy in patient LN tissue— samples that are commonly available and extracted during routine melanoma SLNB staging procedures. In the future, researchers will be able to analyze these pathways to target specific pro- and anti-cancer pathways involved in lymph node metastasis. Melanoma physicians may be able to use information from patient SLNB to further determine which immunotherapy to give patients based on this data.

When melanoma is not found early, it can get into your blood and lymphatic systems and spread to other parts of your body. When this happens, the melanoma is considered metastatic. Because the cancer has spread, surgical removal of tumors is not enough to stop the cancer from progressing, so additional medication is used to kill the cancer cells in the body. For many types of cancer, chemotherapy is used for this purpose. However, for melanoma specifically, a new medication type called immunotherapy has been improving survival compared to chemotherapy. The immunotherapy most commonly used for metastatic melanoma is called ipilimumab/nivolumab, but a new immunotherapy, nivolumab/relatlimab, has recently been approved also for the treatment of metastatic melanoma. Nivolumab/relatlimab works by targeting a particular protein on immune cells called LAG3. When nivolumab/relatlimab binds to LAG3, it activates the immune cell so that it can fight against the cancer. Current research suggests that patients with type II diabetes may have less LAG3 proteins on their immune cells and therefore less places for the nivolumab/relatlimab drug to bind to. Therefore, we hypothesize that nivolumab/relatlimab does not work as well in this population and ipilimumab/nivolumab will work better in comparison for this particular group. In order to test this hypothesis we will gather information from the chart such as treatment start, duration, any recurrences, as well as other variables to fully explore and uncover any differences in response rates between the two treatment groups. We will also collect blood samples from metastatic melanoma patients treated with ipilimumab/nivolumab and nivolumab/relatlimab to look at and compare the immune cells in each group both before and during treatment.

Objectives: Our main goal is to understand how demographic factors influence the medical care patterns of individuals diagnosed with malignant melanoma. We also aim to see how these care patterns and demographics affect the chances of survival in these cases. Rationale: Research has highlighted the crucial role of factors like race and socioeconomic status in determining the severity and outcome of melanoma cases. Yet, we lack comprehensive data about how these factors impact the use of medical care before and after a new melanoma diagnosis, even though these factors are known to influence the disease’s impact. Methods: We are conducting a retrospective study using the Epic COSMOS database, containing records of over 220 million deidentified patients. We’re focusing on patients newly diagnosed with malignant melanoma of the skin. We’ll examine their interactions with healthcare providers six months, one year, two years, five years, and ten years before their diagnosis and categorize them based on their demographic characteristics. We’ll conduct similar analyses for healthcare visits to dermatologists, surgeons, and oncologists after diagnosis. Finally, we will try to understand how these patterns may affect mortality rates. Expected Results: We anticipate that patients with higher socioeconomic status, especially those who are white, will have more prediagnosis dermatology and preventive care visits, as well as more visits to dermatologists, surgeons, and oncologists after diagnosis. We also hypothesize that patients with fewer care visits both before and after diagnosis will face higher mortality rates.

Metastatic melanoma is the most aggressive and deadliest type of skin cancer. Over the past decades, new therapies targeting mutations in these tumors have been developed. Some of the most promising of these therapies target a protein called B-Raf (BRAF) and are called BRAF inhibitors. These inhibitors are effective initially but, over time, patients develop resistance to them, and they are no longer effective. Recognizing this challenge, we propose an innovative approach targeting an important resistance mechanism called metabolic reprogramming. Through this mechanism, cells are able to switch their mode of obtaining energy. In the case of melanoma cells, they usually obtain their energy through a pathway called glycolysis, which allows them to obtain energy quickly. However, when exposed to BRAF inhibitors, these cells have been shown to prefer a pathway called oxidative phosphorylation (OXPHOS), which has been associated with resistance to drugs and metastasis in the setting of cancer. We propose using a drug called atovaquone, which inhibits OXPHOS, against melanoma cells. Atovaquone is an FDA-approved drug with minimal side effects that has been shown to have anti-cancer effects against other types of cancers, such as ovarian and breast cancer, but has not been studied in melanoma. We will first study the effects of atovaquone by itself and then will study the effects of atovaquone in combination with BRAF inhibitors. We hypothesize that atovaquone will have anti-cancer effects against melanoma and that these effects will be stronger in combination with BRAF inhibitors. This innovative approach will study an unexplored treatment avenue and will provide insight into the effects of inhibiting the metabolic pathway of OXPHOS in melanoma.

Pediatric melanoma, a rare but aggressive form of skin cancer in children and young adults, poses a unique challenge for diagnosis and treatment, as it does not present with the same clinical criteria as adult melanoma. Standard recommendations for diagnosis and treatment of melanoma in this patient population are crucial, but an understanding of the biological mechanisms, and how this compares to adult melanoma, is lacking. One mechanism by which cancer cells grow uncontrollably is by preventing their DNA’s protective caps, called telomeres, from getting shorter as they should with each cell division. Research has shown that telomere maintenance may play a pivotal role in the development and progression of pediatric melanoma. This project will explore the role of specific genetic mutations within the telomeres, and the proteins they bind to, in melanoma prognosis in pediatric and adolescent/young adult patients. By elucidating genomic drivers of disease in these patients, we will provide groundwork for subsequent standardization of prognosis and treatment recommendations in this patient population.

Melanomas of the conjunctiva (CM) are very deadly. Knowledge regarding the social factors, especially insurance status such as Medicaid enrollment, that can affect CM mortality is limited. We will be using a national database, called SEER-Medicaid, to investigate whether being enrolled in Medicaid affects survival rates. We will be analyzing all patients diagnosed with CM between the years 1999-2008 and categorizing them as Medicaid or not in Medicaid. We will only analyze adults between the age of 18 and 65, as children may have different Medicaid benefits and elderly individuals may also be enrolled in Medicare. We will used advanced statistics to construct five-year survival curves of CM patients and to evaluate the following variables and how they can affect risk of death: age, race, sex, marital status, duration of Medicaid enrollment, therapy, poverty level, region of the United States, tumor location, rural/urban, tumor size, county English proficiency, county education level, county % minority population, reasons for surgery or no surgery, and other non-standard therapy. Because Medicaid patients have historically been observed to have worse health-care access and survival across many cancer types, we expect that CM patients on Medicaid to also have worse outcomes and survival.

Melanoma is the fifth most common cancer in the United States, with over 97,000 new cases diagnosed in 2023. Localized melanoma has favorable outcomes with a 5-year relative survival rate of 90%. However, metastatic melanoma remains difficult to treat, with a 5-year relative survival rate of 32%. These statistics emphasize the importance of trying to prevent the spread of melanoma (metastasis) and to improve treatment. Previous work has shown that a receptor located on the surface of melanoma tumor cells, called erythropoietin receptor (EPO-R), is associated with metastasis and drug resistance. Research from the field of blood cancer has shown that the interaction of EPO-R and a protein inside the cell called RasGPR3 causes blood stem cells to move into the bone marrow. Notably, recent work has shown that prior to metastasis, a small group of melanoma cells leave the tumor site on the skin and travel to the bone marrow. While in the bone marrow, these melanoma cells start to develop characteristics of the blood stem cells that are naturally found there. Given these findings, we propose that melanoma cells move into the bone marrow where their levels of EPO-R and RasGRP3 increase, which allows melanoma cells to migrate to different parts of the body (metastasize) and develop drug resistance. Previous work in our lab has allowed for the creation of a new compound, called URV3, that blocks EPO-R. In our studies, URV3 has been effective in preventing the movement of leukemia cells and blood stem cells. We aim to use URV3 to block EPO-R in melanoma cells and decrease cell movement by lowering EPO-R and RasGRP3 levels. We also predict that URV3 will increase the ability of melanoma cells to respond to treatment.

Despite being the second most common group in the U.S. to be diagnosed with melanoma after non-Hispanic whites, Hispanics have significantly more-advanced-stage diagnoses and significantly higher mortality rates from melanoma than do non-Hispanic whites. The reasons behind this are multifactorial and include the important aspect of decreased melanoma awareness in this population, as well as decreased access to care. Our proposed project will take place at a clinic for the underserved and include a volunteering board-certified dermatologist and patient education about prevention and recognition of melanoma, as well as the ability to schedule an appointment with the volunteering dermatologist, thus uniquely affording participants both self-empowering education and real access to specialist care. This is a practical, boots-on-the-ground project that could serve as an effective example of improving access to care and decreasing disparities in melanoma awareness and prevention. Research is critical to assess efficacy and to appraise systems utilized to draw conclusions and make recommendations for future possible models.

Background Explained: Utah has the highest incidence of melanoma per 100,000 individuals in the United States. While fewer people from minority communities such as Native Americans, Hispanics/Latinos, and African Americans develop melanoma, they tend to have lower survival rates. Challenges in accessing dermatology care, economic hurdles, and limited health knowledge are suspected to play a part in these disparities. We aim to understand from patients, providers and community leaders how these factors interplay to affect optimal melanoma care with the goal to develop targeted, actionable interventions in the future. Importance: By pinpointing the specific obstacles faced by minoritized groups in Utah with regards to melanoma diagnosis and optimal treatment, we will work collaboratively with our community partners to create targeted interventions that resonate with them to improve melanoma outcomes. populations. Method: Our research involves gathering insights through focus group discussions with melanoma patients, healthcare workers, and minoritized community leaders. Before these discussions, participants will be surveyed to assess their perceptions, beliefs, and knowledge regarding melanoma and its care disparities. These conversations will delve into the real-life challenges they face, informed by their personal experiences and cultural contexts. We aim to capture the subtleties of these challenges through careful listening and analysis. Expected Insights: We expect to identify specific barriers and cultural nuances that hinder optimal melanoma care for these communities. The knowledge gained will inform policy changes and suggest modifications in clinical practice, all designed to reduce the disparities in melanoma outcomes.

Melanoma is a tragic disease that is further complicated because scientists do not completely understand the causes, and this prevents clinicians from giving the most accurate prognosis and effective treatments. In this Melanoma Research Foundation application, a research-oriented medical student will apply a recent biological discovery in skin cancer and transform this discovery into a new prognostic tool. This will be accomplished by analyzing groups of patient biopsies from healthy volunteers to those diagnosed with melanoma using modern state-of-the-art microscopy and advanced statistical methodologies. At the end of this oneyear study, modern insights will be established that provide much needed information about how melanoma develops, and this has great potential to assist clinicians when informing patients on their risk of skin cancer, the likelihood of metastatic disease, and potentially reveal which type of treatment is best for newly diagnosed melanoma patients.