Multi-cancer Early Detection

PROJECT SUMMARY/ABSTRACT Cancer is a leading cause of mortality in the U.S. Screening reduces mortality from several of the most common (colorectal, breast, uterine cervix, and lung) cancers but most cancer types, accounting for 70% of cancer deaths, are not screened due to limitations in technology and low positive predictive value, driven by low incidence of each individual cancer type. It has been argued that multi-cancer detection tests might address this critical long-term gap in population health. To avoid false-positive results, commercial multi-cancer test developers train performance on high specificity goals at the penalty of low sensitivity for early-stage cancers, and current tests may more or less accurate depending on the organ/type of cancer. This application proposes to use unique sample archives to address key scientific questions. Specifically, there are relatively limited assessments of 1) how well and at what interval multi-cancer test predict the development of clinical cancer (indolent vs lethal) among asymptomatic individuals (prediagnostic performance study); 2) how to evaluate or validate promising liquid biopsy-based biomarkers in various risk populations; and, 3) how to facilitate the development of high-throughput, sensitive assay methods to validate biomarkers that are useful in early detection of early-stage cancers or their lethal precursors. This application is in direct response to NOSI (NOT-CA-23-004) “Utilization of Cohorts and Prospective Study Designs for Liquid Biopsy Assay Validation for Early Detection of Cancers,” in which NCI has encouraged partnerships between technology developers and population-based cohort/biorepository researchers to facilitate multi-cancer detection test investigations in the appropriate populations, and encouraged applications that investigate the use of existing cohort samples and samples from ongoing prospective collections for analytical and clinical validation of assays for earlier detection of cancer. With our biomarker candidate marker library, extensive sample archive, and unique access to a state-of-the-art assay and analytical platforms, accelerated implementation of multi-cancer detection testing in clinical practice is anticipated by addressing impactful scientific questions beyond the tactical focus of the commercial lens.