PROJECT SUMMARY Early detection of cancer provides one of the most effective ways to reduce cancer related morbidity and mortality. However, most malignancies including brain and head and neck cancers do not have effective minimally invasive strategies for early detection. Unfortunately, early detection is hindered by several factors, including the lack of suitable tests and cost. One of the chief challenges in developing non-invasive tests is the identification of the appropriate biofluid and specific markers. While blood-based testing has shown promise, many cancers are not easily detected in the circulation. Over the past two decades, DNA released from cancer cells has emerged as a specific biomarker of cancer. We have previously developed sensitive methods for the simultaneous detection of multiple DNA based analytes from a small quantity of starting material in a variety of biospecimens. We have extensive preliminary results that biofluids, such as cerebrospinal fluid (CSF) and saliva, associated with certain cancers are significantly enriched in released tumor DNA (rtDNA) compared to blood. In addition, our group has an ongoing relationship with an industrial partner to translate our promising technology into the clinical realm. This proposal will build on those strengths to develop assays for the sensitive and specific detection of brain and head and neck cancer in CSF and saliva, respectively. A non-plasma based “liquid biopsy” approach for the earlier detection of cancers difficult to detect in the blood would represent a significant medical advance.

PROJECT NARRATIVE We have demonstrated that biofluids in close proximity to cancers are significantly enriched for levels of released tumor DNA, which permits for greater sensitivity and potentially specificity. In this proposal we will utilize a multi-analyte approach including mutations, aneuploidy, fragmentomics and methylation to develop liquid biopsy approaches for pre-neoplastic and neoplastic conditions involving the brain and head and neck by analyzing cerebrospinal fluid and saliva respectively. We will work closely with our industrial partners, Belay Diagnostics, to validate the performance of our assays and develop CLIA certified tests ready for clinical implementation.