Defining a Neuron-pericyte Axis via the Neuropeptide Receptor PAC1 in Melanoma Development and Progression

At a Glance

Dr. Alexander Birbrair, assistant professor in the Department of Dermatology, is leading a crucial research project aimed at advancing treatments for melanoma. Melanoma is the fifth most common cancer in the United States, and it has disproportionately higher mortality rates in racial and ethnic minority populations. Cancer and the nervous system bear a close relationship, and the team is particularly interested in understanding how signaling from a receptor, called PAC1, impacts melanoma progression. The results of this project could inform clinical testing for medications targeting the PAC1 signaling pathway to treat melanoma, ultimately improving survival rates for all melanoma patients.

The Challenge

Melanoma is the fifth most common cancer among both men and women in the United States, with approximately 325,000 new cases and 57,000 deaths worldwide each year. There are long-standing racial disparities for melanoma patients, due to late diagnosis in minorities. Despite advances in understanding and treating melanoma, the overall survival rates for patients with melanoma remains poor, with most individuals succumbing to the disease despite appropriate therapy. This highlights a pressing need for new and better treatment approaches.

Project Goals

Cancer and the nervous system bear a close relationship, and the research team’s ultimate goal is to understand how signals from nerves inside melanoma tumors affect the cancer’s progression. They are particularly interested in a specific receptor, called PAC1, which plays a role in this signaling. The team’s goal will be addressed through three specific aims:

1. Understand PAC1’s role in tumor cells: The team will study how PAC1 signaling affects certain cells within melanoma tumors.
2. Test PAC1 inhibition as a treatment: They will test a PAC1 inhibitor combined with immunotherapy in mice to see if it effectively treats melanoma.
3. Examine PAC1 in human melanoma: The team will analyze human melanoma tissues samples to see how PAC1 is expressed, helping to determine its importance as a target for treatment.

The results of this research could lead to new clinical trials and treatments targeting the PAC1 signaling pathway. This could significantly improve the outcomes for melanoma patients, especially those from racial and ethnic minority groups who have disproportionately higher mortality rates. Dr. Birbrair’s innovative approach aims to bridge the gap between cancer and nervous system research and strives to increase survival rates for all patients.