MethylScan for Early Detection of Liver and Lung Cancer

PROJECT SUMMARY The long-term goal of this SBIR Phase II project is to develop and market a commercially viable, blood-based methylation profiling test that can detect and locate multiple types of cancer early. Clinical intervention in the early stages of cancer can greatly improve the survival of cancer patients. Despite the tremendous demand for early detection methods in clinical practice, few commercial tests exist in the market. To address this unmet need, in Phase I, we developed and validated a cell-free DNA Reduced Representation Bisulfite Sequencing assay, MethylScan assay, to interrogate the methylation profile of cfDNA. The MethylScan assay was highly reproducible and reliable at low input quantities of DNA and achieved high sensitivity and specificity for detecting liver cancer. DNA methylation is established during early mammalian cell differentiation and plays an important role in the development and progression of cancer; thus, it is an ideal biomarker not only for pan-cancer detection but also for identification of tumor tissue of origin. The proposed project will translate the MethylScan assay to a surveillance product for liver cancer and expand its intended use for early lung cancer detection in patients with indeterminate lung nodules. In this Phase II study, our specific aims are as follows: Aim 1) Optimize MethylScan assay and the workflow of MethylScan Test; Aim 2) Perform a clinical validation to evaluate MethylScan test for early detection of HCC; Aim 3) Perform a clinical validation to evaluate MethylScan test for early detection of lung cancer in patients with indeterminate lung nodules. The MethylScan test will be used to perform cancer prediction in a cohort of 200 early HCC patients, 70 early lung cancer patients with malignant lung nodules, 200 patients at high risk for HCC or 50 patients with benign lung nodules. Participants in the clinical validation study will be recruited from Midwest and West Coast sites. The outcome of this project will support large clinical trials for MethylScan test as a surveillance approach for patients at risk of liver and lung cancer. The data collected will be discussed with FDA in a pre-submission meeting.