Identification of Risk and Early Detection Biomarkers for Liver Cancer
Abstract
The significance of this project for the military is highlighted by its close alignment to the FY22 PRCRP Topic Area of Liver Cancer, the Military Health Focus Area Gaps in cancer research that may affect mission readiness, and the Overarching Challenges Prevention and Diagnostics. Hepatocellular carcinoma (HCC) incidence has been rapidly increasing in the U.S. for decades and is one of the most lethal cancers. While treatable and curable at early stages, the majority of HCC cases are diagnosed at a late stage when survival is typically reduced to less than 1 year. One of the major risk factors for the development of HCC is liver cirrhosis, a chronic, incurable and progressive fibrotic disease of the liver, resulting from fatty liver disease, alcoholism, and HBV or HCV infection. With millions of people being impacted by one of these major liver diseases in the U.S., HCC is prevalent in a significant proportion of military personnel, Veterans and their beneficiaries. Thus, this is a critical problem for U.S. men and women who are serving or have served in the military forces and their families. The lack of a diagnostic for earlier detection of pre-symptomatic HCC means that the majority of all HCC cases are only diagnosed when a patient shows up with symptoms at an advanced stage. Unfortunately, at this, frequently inoperable, stage of spread of disease no cure is possible. Consequently, the key for improving survival of patients with HCC is earlier detection before symptoms occur and before the cancer becomes metastatic. Indeed, patients who are diagnosed at an early stage have a 70% chance of 5-year survival with surgical resection or liver transplantation. The current accurate diagnosis can only be achieved by costly, invasive liver biopsy or imaging, which are not suitable for screening of high-risk populations, such as individuals who have progressive liver disease with cirrhosis, in the community setting. The current lack of cost-effective, diagnostic blood biomarkers that can detect HCC earlier in high-risk patients with cirrhosis when cure is possible or can predict the risk of developing HCC is the major hurdle for improving survival of patients who develop HCC. If such a diagnostic or predictive test could be developed, patients diagnosed earlier for HCC than currently happening or at highest risk of developing HCC would undergo further follow-up tests such as imaging and biopsy and, if confirmed, have surgery or liver transplantation. Early intervention due to early detection is the only feasible scenario for improving outcome and survival in HCC. Consequently, it is a critical unmet medical need to discover and validate new biomarkers, ideally in the blood, that are able to detect HCC earlier when patients are likely to benefit and to develop a diagnostic test that is cheap and can be performed in a primary care physician s office. If we are able to identify such biomarkers and develop a highly accurate test, clinicians will be able to test high-risk individuals routinely for any signs of HCC. For these reasons, we propose a highly innovative and transformative project to identify such protein biomarkers in blood that can detect HCC earlier in asymptomatic, high-risk individuals such as cirrhosis patients using a cutting-edge, next-generation proteomics technology. We will test the hypothesis that specific protein changes in blood can accurately diagnose patients with HCC years before standard diagnosis among cirrhosis patients and that, by identifying and validating early detection biomarkers, we will be able to improve outcome and survival of patients with HCC. Our proposed aims are to further validate pre-diagnostic blood proteins discovered in our preliminary studies of two population cohorts as biomarkers for HCC development in a third population of healthy individuals with many years of follow-up that includes several hundred cases of HCC diagnosed years after blood collectio
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310965
Entities
People
- Towia A Libermann
Organizations
- Beth Israel Deaconess Medical Center
- United States Army