Prostate-Specific Membrane Antigen (PSMA) in Hepatocellular Carcinoma
Developmental Research Program Overview
This proposal's long-range objective is to improve outcomes for patients with hepatocellular carcinoma (HCC). HCC is a major global burden of morbidity and mortality, and its occurrence in the United States has increased markedly during the past 30 years. HCC is diagnosed mainly by imaging using contrast-enhanced CT or MRI. This is critical because it impacts decisions for surgical, locoregional and medical therapies and for monitoring for disease recurrence and progression after treatment.
However, there are significant limitations of existing morphologic or contrast medium enhancement-based criteria for both diagnosis of hepatocellular carcinoma and assessing response to treatment. As such, in patients at high-risk of HCC with negative or inconclusive cross-sectional imaging, or with liver lesions but without cirrhosis or conventional risk factors or known primary malignancy, or after surgical, locoregional or systemic therapies for known HCC, there exists a critical need for a sensitive and specific molecular imaging technique for imaging of hepatocellular carcinoma. We have identified expression of prostate-specific membrane antigen (PSMA) in the majority of HCCs.
This proposal in the Developmental Research Program in the Mayo Clinic Hepatobiliary SPORE seeks to provide understanding of PSMA expression in both HCC and non-HCC liver tumors, with the goal to determine if PSMA represents a potential diagnostic and therapeutic target in HCC.
- David A. Woodrum, M.D., Ph.D.
- 2019-2021 Awardee
68Ga-PSMA and 177Lu-PSMA are being developed as diagnostic PET imaging and therapeutic agents, respectively, in prostate cancer. As such, PSMA represents a potential diagnostic and therapeutic target in HCC. However, development of PSMA as a diagnostic and therapeutic target for improving the diagnosis and outcomes of hepatocellular carcinoma will require further understanding of PSMA expression in both HCC and non-HCC liver tumors.
The specific aims of this proposal are: 1) To determine any associations between PSMA expression and clinical, pathologic and radiologic features of HCC; 2) To determine the expression and localization of PSMA in benign and non-HCC primary and secondary malignant liver tumors and determine potential associations between PSMA expression and clinical, pathologic and radiologic features of those tumors; and 3) To determine the expression of PSMA in the serum of patients with HCC and CCA as well as cirrhosis, PSC or no evidence of chronic liver disease.
We are using a combination of clinicopathologic-radiologic data, immunohistochemical and biochemical methods, and patient-based approaches to systematically investigative the tissue and serum expression of PSMA in HCC and non-HCC liver tumors and associations of PSMA with clinicopathologic and radiologic features in HCC. This proposal's successful completion will elucidate the specificity of PSMA in HCC and provide a molecular framework for translating diagnostic 68Ga-PSMA PET and therapeutic 177Lu-PSMA to clinical trials for HCC. Overall, this proposal has the potential for high clinical impact given the lack of molecular imaging agents in HCC. These findings will likely generalize to other hepatic tumors that express PSMA and PSMA as a tissue or serum biomarker in HCC.