Novel Circulating Biomarker for Hepatocellular Carcinoma
Abstract
Objectives and Rationale Hepatocellular carcinoma (HCC) is the most common form of primary liver cancer, and it is a highly lethal disease. While the disease burden of liver cancer continues to increase in the United States, there are currently no tests beyond radiographic images to monitor disease progression. Imaging tests can`t predict treatment response nor affect the selection of specific treatment in patients with liver cancer. With regard to blood-based biomarkers for HCC, alpha-fetoprotein (AFP) is a traditional diagnostic and prognostic biomarker with limited accuracy. Therefore, there is a significant, unmet need to develop accurate and clinically relevant biomarkers to optimize the management of liver cancer. Circulating tumor cells (CTC) are a novel blood-based biomarker that allows isolating cancer cells noninvasively from the peripheral blood draw. Our group has developed a novel CTC detecting technology with high sensitivity for detecting liver cancer CTCs. The proposed CTC platform allows further biologic characterization of CTC by staining specific proteins in the CTC. It also allows measuring a panel of genes expression level within isolated CTCs, which reflects the biological process of tumor cells in a noninvasive manner. Our research study aims to enumerate biologically distinct liver cancer CTCs and investigate the association between the specific subtype of CTCs and liver cancer grade, stage, and progression after treatment. Successful completion of the project will improve disease monitoring, prognosis prediction, and selection of treatment in the era of precision medicine for liver cancer. The PI’s Career Goals in Cancer Research Dr. Ju Dong Yang has built up a strong research base and knowledge in liver cancer, which is one of the Fiscal Year 2019 Peer Reviewed Cancer Research Program (PRCRP) Topic Areas. He published extensively in the field of liver cancer. Dr. Yang plans to develop precision medicine-based biomarker research career in liver cancer. Department of Defense PRCRP Career Development Award will provide Dr. Yang the key support needed to establish expertise and investigate an exciting area of precision medicine in the field of liver cancer under the mentorship of Dr. Lu, widely acknowledged to be one of the world’s leading experts on liver cancer basic science research and Drs. Tseng and Posadas, world experts in cancer liquid biopsy research with active National Institutes of Health grants on CTCs. Applicability of the Research What types of patients will it help, and how will it help them? These translational findings will benefit patients with liver cancer for better prediction of disease progression. It also may justify a future clinical trial with Sadenosylmethionine (SAMe). SAMe might be an effective treatment option particularly in HCC patients with CTCs that have SAMe susceptible cancer promoting gene overexpression. What are the potential clinical applications, benefits, and risks? CTCs will help clinicians to monitor and predict disease progression and may provide biological characteristics of liver cancer without needing an invasive procedure, such as liver biopsy. As it involves a simple peripheral blood draw, there is a minimal/no risk of this test. The test may also help clinicians to provide individualized treatment for liver cancer patients based on the tumor biology of each patient. What is the projected time it may take to achieve a patient-related outcome? We anticipate completing the proposed study in 3 years. Once the proposed study is completed successfully, we will conduct a large-scale multicenter prospective study, which may take an additional 2-3 years to complete. Hence, the proposed technology could be available in routine clinical care in 5-6 years. In addition, we will also conduct an early phase clinical trial that will evaluate the efficacy of SAMe in HCC patients with CTCs that have SAMe susceptible cancer promoting gene overexpression
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010800
Entities
People
- Ju Dong Yang
Organizations
- Cedars-Sinai Medical Center
- United States Army