Investigating miR-9-5p and Its Targets as Interventional and Clinicopathologic Predictors of Laryngeal Cancer Racial Disparate Outcomes
Abstract
Scientific Objective and Rationale: 80-90% of head and neck cancers involve the anatomic sites of the oral cavity, oropharynx, and larynx. Among these three anatomic sites, laryngeal cancer harbors the lowest 5-year survival rate (about 30-40%). It is also associated with high rates of suicide due to treatment-related comorbidities and reduced quality of life. Additionally, laryngeal cancer disproportionately burdens Black people as they maintain a higher incidence of this cancer, present with higher stage disease, and have increased mortality. These factors contribute to the lower 5-year survival rate seen within Blacks compared to any other race. The disparity in survival remains even after considering socioeconomics and environmental factors. Currently, there is no clear understanding of the role of biology in the disparate outcomes. I believe it is imperative to understand if biology contributes to the outcome while also identifying biomarkers that can help to predict outcomes for at risk populations. My preliminary studies have demonstrated microRNA-9-5p (miR-9) has significantly lower expression in Black laryngeal cancers as compared to White. My work has shown that low miR-9 is associated with decreased mortality and increased chemoresistance. ABCC1 is regulated by miR- 9 and my work has shown that high protein levels of ABCC1 is associated with increased chemoresistance and poor survival. Based on these findings, in my proposal, I seek to understand if there are unique biochemical pathways triggered in laryngeal cancers where miR-9-5p expression is low compared to if it is high. I also seek to exploit miR-9 and its target ABCC1 as predictors of chemotherapeutic resistance and poor survival. I desire to identify miR-9 pathways and targets that may contribute to racial disparities of laryngeal cancer, reducing cancer health disparities in the head and neck and harnessing the information in these pathways may provide additional therapeutic targets. Principal Investigator Cancer Research Goals: My long-term career goal, as a physician-scientist and pathologist, is to be at the forefront of head and neck cancer racial health disparities research while impacting the management and treatment of these cancers. In order to accomplish my goal, it is necessary that I have dedicated time to gain expertise in tools of computational biology--tools that are now key players racial health disparities and pathology and critical in shifting the diagnosis, management, and treatment of cancer. My research proposal marries computational biology and molecular pathology. The data obtained from the research proposal will lay the groundwork for future studies, grants, and opportunities to move me into the forefront of cancer health disparities. Clinical applications, benefits, and risk: If miR-9 and its target, ABCC1, prove to be clinicopathologic predictors of treatment and survival outcome, the use miR-9 and ABBC1 in the clinical setting would be for all patients with laryngeal cancer, irrespective of clinical stage. miR-9 and ABCC1 can assist in predicting a patient’s response to cisplatin (the drug used to treat all head and neck cancers) and/or predict the likelihood of patient survival. Low miR-9 may indicate other therapies or even more aggressive treatment is necessary. Conversely, elevated miR-9 may be used to reduce treatment burden. Race could also be an indicator to test for these biomarkers. In the manner a pathologist would use it, I foresee no risk to using this miRNA in a clinical setting. Overarching Challenges: 1. Develop strategies and biomarkers to predict cancer risk, treatment resistance, recurrence, and advanced disease to mitigate risk target populations. 2. Improve prevention strategies, diagnosis, treatment, and outcomes for patients in underserved or under recognized populations (e.g., military populations, rural populations, communities of color, other minorities, and women) This
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Dec 28, 2022
- Source ID
- W81XWH2210935
Entities
People
- Kristianna Fredenburg
Organizations
- United States Army
- University of Florida