Development of Novel Embolization Therapy for Hepatocellular Carcinoma
Abstract
SCIENTIFIC OBJECTIVE Liver cancer, or hepatocellular carcinoma (HCC), is a common cause of cancer deaths worldwide. Due to increasing rates of obesity and hepatitis B and C, HCC is increasing in incidence. Most HCC patients are ineligible for a curative liver transplant and instead receive some other therapeutic treatment such as transarterial embolization (TAE) or transarterial chemoembolization (TACE). In these procedures, microparticles, with or without chemotherapy, are delivered through a small catheter directly into the artery that supplies the tumor, blocking blood flow. However, TAE and TACE leave residual untreated tumor leading to high rates of tumor recurrence. Our recently published results show that the natural phytochemical caffeic acid (CA) combined with small particles for embolization causes extensive regression of liver tumors implanted in rats. Treatment of HCC cells in culture with CA disrupts metabolism and causes cell death. The objective of this project is to test small particles loaded with CA compared to small particles without CA in treating tumors in a large animal model (Marmota monax, woodchuck). The woodchuck tumors develop spontaneously in diseased liver and are the closest analog to human HCC that we will treat using the exact methods as done in current clinical practice. Showing the efficacy of our novel catheter-based treatment for HCC in animals will lead to clinical trials and transformation of clinical practice for the benefit of liver cancer patients and their families. PRINCIPAL INVESTIGATOR CAREER PLAN The principal investigator - Luke R. Wilkins, MD - is a clinical interventional radiologist specializing in minimally-invasive, image-guided procedures. A significant component of Dr. Wilkins clinical work involves locoregional treatment of advanced hepatocellular carcinoma (HCC) with research efforts devoted to translational research. This project will enhance Dr. Wilkins career path toward becoming an independent investigator in the field of interventional oncology. Ultimately, Dr. Wilkins seeks to initiate a program where pre-clinical research protocols are investigated in a translational research lab in order to initiate clinical trials. As a clinician scientist he is able to identify areas in need of clinical improvement and, through experience in team science, merge image-guided interventions, cancer biology, and molecular imaging. Dr. Wilkins seeks to lead research projects that go from bench-to-bedside to define and refine innovative therapies. RESEARCH APPLICABILITY The proposed research utilizes a novel anti-tumor agent CA and a delivery system of porous beads to occlude the blood flow to the tumor. Our research plan allows for effective translation of results into a clinical trial, speeding development toward clinical implementation. Our preliminary data suggest that patients with HCC will benefit greatly by improved tumor response, improved tolerance to therapy, and increased chances of cancer cure. MILITARY BENEFIT The proposed research has high applicability to the military and Veteran patient population. The incidence of HCC has been increasing globally with a 3-fold increase in the number of new HCC cases in the United States alone. This rising incidence is reflected in the Veteran population and is now greater than 9.1 out of 100,000 person-years. Risk factors for development of HCC include hepatitis C virus, hepatitis B virus, alcoholic cirrhosis, and diabetes. These risk factors have a high prevalence within the Veteran population. This project promises to improve outcomes for catheter-based treatments of HCC.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Nov 19, 2019
- Source ID
- W81XWH1910607
Entities
People
- Luke Wilkins
Organizations
- United States Army
- University of Virginia