Melanoma is one of the most common cancers in the United States. We know that early diagnosis improves how patients diagnosed with melanoma do over time. New moles noticed by patients or doctors in adults are often worrisome for early melanoma. However, many of these moles are not found to be melanoma once removed. Using a handheld microscope, called a dermatoscope, improves dermatologists’ ability to find melanoma, but not every dermatologist uses a dermatoscope, and in areas where there are very few or no dermatologists, primary care doctors are unlikely to use them. Automatic computer diagnosis tools could be a cheaper and accurate way to help these doctors screen for melanoma in new lesions. We will test these tools on new moles and melanomas. These results will help us understand the potential uses of automatic diagnosis tools in new lesions in practice to help diagnose melanoma.

2022 Medical Student Award – Emily Cowen

Career Development Award – Sixue Liu, PhD

Mucosal melanoma (MM) is a rare form of melanoma with poor survival outcomes. Data on treatment for MM is limited to results from studies on cutaneous melanoma or from small cohorts of MM patients. The Veterans Affairs population is one of the largest U.S. healthcare networks and includes individuals traditionally under-represented in clinical trials (older age and diverse ethnic and racial backgrounds). Using data from the Veterans Affairs will allow us to examine one of the largest cohorts of MM patients.

Immune checkpoint inhibitors (ICIs), specifically anti-programmed death-1 (PD-1) therapies (nivolumab and pembrolizumab) and anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) (ipilimumab), have emerged as promising therapeutic candidates for treatment of MM, but studies have thus far yielded mixed results. A large-scale outcomes study in patients treated with immunotherapy may provide us with additional information to guide therapy choice based on real-world data.

Survival among MM patients varies by anatomical location, possibly due to anatomical surgical constraints, different lymphovascular supplies, different stages at diagnosis, different tumor mutational burdens, and different immune system characteristics by site. We will examine whether site of primary tumor predicts improved survival with ICI treatment.

Medical Student Award – Nicole Trepanowski

For patients with melanoma, timely diagnosis and prompt treatment are important for optimal outcomes, but some groups of patients may face barriers to accessing dermatology care, leading to treatment delay and disease progression. These potential differences in health outcomes between groups of patients are referred to as health disparities. Health disparities may manifest as a result of unequal opportunities or unequal access to resources that arise from variations in geographic locations, income levels, race/ethnicity, or other factors. To better understand the social and geographical factors underlying potential disparities in melanoma patients, I will extract Social Vulnerability Index (SVI) data for a group of de-identified patients with melanoma selected from a state cancer registry. The SVI is a tool recently developed by the Centers for Disease Prevention and Control (CDC) and comprises 15 different social and geographical factors at the neighborhood level, including those related to socioeconomic status (SES), minority status, and other social determinants of health (SDOH). While the SVI has lately been applied in other cancer care contexts, it has yet been applied to the melanoma context. The results of this research project will enable us to better identify vulnerable communities that may benefit most from a place-based strategy to prevent excess deaths from melanoma.

Medical Student Award – Tiffaney Tran

Pigmentation, or the coloring of the skin, hair and mucous membranes, has been shown to influence melanoma risk. Most, if not all traits and diseases, have a genetic component that influences development or susceptibility. These genetic components, or loci, can be determined using genome-wide association studies (GWAS). GWAS studies associate millions of relatively common genetic modifications between a healthy population and a population containing a trait or disease of interest. The assignment and interpretation of these genetic modifications has also proved challenging. In this study, we aim to utilize a series of computational approaches to determine whether GWAS associations between pigmentation and melanoma are truly causal rather than due to coincidence. We then use a machine learning algorithm to identify and assign a likelihood of gene involvement for each trait. This information will enable us to further examine the shared biological mechanisms between pigmentation phenotype and melanoma.

Medical Student Award – Sarem Rashid

Findings from this grant will shed light on 1) how stemness is sustained by modulating PI3Kδ signaling in T cells using FDA-approved drugs and 2) how transcription regulation in T cell mitochondria contributes to tumor immunity.

Medical Student Award – Guillermo Omar Rangel Rivera

While immunotherapy treatment has radically improved the outcomes of patients with advanced melanoma, around half of patients have no response. This is in part because of cancer cells’ altering of themselves so that they cannot be identified and eliminated by immune cells. The long-term goal of this project is to determine how the natural compound resveratrol undoes this alteration so that cancer cells can be recognized and eliminated by the body’s immune system.

Medical Student Award – Lauren Morehead

According to the latest published statistics by the NIH, there are almost half a million individuals who are cancer survivors after having been diagnosed with cancer at some point in their childhood or adolescence. These individuals may have a higher chance of developing additional types of cancer as they age, be it due to their family history, treatments they received for their cancer as children, or due to factors in their environments. Not much is known about the frequency by which these individuals develop a type of skin cancer called melanoma; after their first initial diagnosis of cancer as children or adolescents. Furthermore, although adult cancer survivors are monitored yearly with skin exam check-ups to look for early signs of possible skin cancer, the childhood cancer survivor population does not currently undergo such rigorous monitoring after they are treated for their initial cancer. Therefore, to
gain a better understanding of the frequency by which childhood cancer survivors develop melanoma we will be conducting a study to review the charts of hundreds of patients who are now childhood cancer survivors, with the goal that we can offer future patients better monitoring plans to hopefully guide future surveillance and prevention strategies.

Medical Student Award – Salma El-Behaedi

While several medications, immune stimulating agents, and radiation therapies have been developed and used for the treatment of melanoma, the treatment options often have systemic toxicity effects and can be limited in their treatment of metastasis. For melanoma, there are often cutaneous lesions that allow for direct destruction, and the destroyed cancer cells present a marker that can help stimulate our own immune cells to detect and kill other melanoma cells in the surrounding. Thus there is an unmet opportunity to use both the type of treatment options: local therapy and a systemic therapy, to help cause local destruction and boost the immune response against these cancer cells. Previously our groups have developed a drug delivery platform using bioadhesive, biodegradable nanoparticle molecules; these have increased local activity while decreased systemic effects—therefore it increases thesafety and efficacy of the drugs. The purpose of the research is to use these nanoparticles loaded with chemotherapy to target melanoma nodules and metastatic melanoma in conjunction with local or systemic immune stimulating agents. We will also be using nonadhesive nanoparticles that have increased drug retention and engineerable size to target lymph nodes to help boost the anti-cancer effects by encapsulating an immunostimulant. The approach is unique as we are proposing a method to kill the cancer cells using the nanoparticles and another immunomodulatory molecule to help train the immune system to recognize the metastatic melanoma cells. Targeting the lymph nodes will help boost the body’s own anti-cancer response while theoretically decreasing the off-target and systemic effects. We will be using the nanoparticles with chemotherapy for local injections against nodular melanoma and also assess
the combination therapy with local and systemic immunostimulation including CpG, anti-PD1, and our own immunostimulant loaded nanoparticles. We hypothesize that the nanoparticle delivery of these agents in conjunction with these molecules will lead to efficient regression/ elimination of melanoma and metastatic lesions.

Medical Student Award – Jungsoo Chang

Hybrid cells, in circulation and in the tumor are reprogrammed cancer cells displaying immune cell mimicry—insights into their impact on tumor progression, immune cell interaction, and regulation of the tumor microenvironment have not yet been explored. In this study, I aim to characterize both the genotypes and phenotypes of hybrid cells in UM, drawing comparisons between hybrid cells across the metastatic cascade that will ultimately aid in our understanding of UM disease progression. Furthermore, I will evaluate RUNX1 pathway phenotypes across the metastatic cascade, as a means for facilitating hybrid cell dissemination. The study of hybrid cells in UM has great potential to uncover new biologic insights to neoplastic cell dissemination and ultimately lead to a greater understanding of targetable mechanisms of this process.

Medical Student Award – Ashley Anderson