• Ways to improve comparability of MCED test performance for better matching to a patient’s individualized cancer risk              
• Best options for workups when cancer cannot be imaged              
• The role of single-cancer tests as reflex for positive MCED results​​

• NIH-wide SBIR and STTR programs 
• Funding opportunities for Early Cancer Detection 
• Application tips and assistance for awardees and applicants​​​​

• Challenges around existing cancer screening rate data sources – inaccuracy, inaccessibility, incompleteness
• Impact of these challenges on early detection test development 
• Proposed solutions and opportunities to get involved​​

• Trade-offs between sensitivity and specificity                
• The pros and cons of broad vs. more narrow initial training                
• Accounting for patient risk for more targeted screening​

Broad adoption of MRD testing is still evolving as the evidence base grows across multiple cancer types and intended uses. Insights from clinical trials, published evidence, and medical policies give perspective on utilization and where the space is headed.

Advances in cancer care include the recognition of the transformational importance of evolving endpoints such as MRD. What will it take to drive a shift toward MRD recognition and adoption? Education and awareness for all stakeholders in the ecosystem, including patients, providers, payers, and regulators is key to addressing Health System barriers in adoption of MRD as an endpoint and ensuring timely access to innovation for cancer patients.

Circulating cfDNA assays for monitoring treatment response and disease progression in individuals with cancer typically rely on prior identification of tumor-specific mutations. Here, we describe a tumor-independent and mutation-independent approach (DELFI-TF) using low-coverage whole genome sequencing to determine the cfDNA tumor fraction and validate the method in independent cohorts of patients with colorectal or lung cancer.

Analytical sensitivity under the tumor-informed paradigm for MRD detection shows benefits from targeting more variants, with improvement translating to clinical performance. Traditional NGS approaches face a trade-off between breadth of genomic regions interrogated (number of variants targeted) and depth of sequencing (per target). We developed two tumor-informed MRD platforms: WES-informed hybrid capture assay (first generation, targeting hundreds of variants) and WGS-informed MAESTRO assay (second generation, targeting thousands of variants) designed to bridge this breadth-depth trade-off.  Case/control cancer cohorts spanning diagnosis through monitoring demonstrate striking benefit to recurrence lead times and ctDNA detection sensitivities at single-digit (and below) ppm levels.

Minimal residual disease (MRD) testing has traditionally provided early insights into cancer recurrence risk, but without a clear path to guide treatment decisions. This presentation will show how ultrasensitive, next-generation MRD assays such as Foresight’s CLARITY™ are shifting the role of MRD from passive monitoring to active clinical utility. The session will highlight how actionable MRD results can enable escalation or de-escalation of therapy, support earlier intervention when outcomes can still change, and reduce unnecessary procedures and tests, ultimately helping to drive measurable impact in cancer patient outcomes.

• NIH-wide SBIR and STTR programs 
• Funding opportunities for Liquid Biopsy for Cancer Development  
• Application tips and assistance for awardees and applicants​​
  

• Leveraging the All of Us dataset for developing and validating next-generation diagnostics for diverse populations
• Exploring how our diverse dataset (particularly lifestyle, environment, and geographical distribution) can aid development and implementation of liquid biopsies for cancer
• How can the dataset be a critical resource for validating novel liquid biopsy assays
  

As circulating tumor DNA (ctDNA)-based assays transition from research settings to broader clinical application, studies have revealed significant variability in validation practices across institutions. This session will explore how clinical validation guidelines are addressing these inconsistencies by offering a standardized framework to support more widespread and uniform adoption. It will also examine persistent barriers and practical challenges as testing expands beyond specialized centers. Emphasis will be placed on the pivotal role of evidence-based standards in supporting clinical implementation, while fostering both innovation and confidence in ctDNA-based liquid biopsy applications.

Biospecimens are the essential starting materials for the biomarker assays that enable precision medicine and preanalytical factors can directly influence molecular results from assays conducted for basic research, biomarker discovery, and biomarker validation, and can also influence the development of clinical assays. The presentation will focus on the role of biospecimen science in context of cfDNA as a predictive, prognostic clinical biomarker, MRD assays, and The Cancer Moonshot Biobank (moonshotbiobank.cancer.gov), which is a NCI-sponsored study that aims to accelerate cancer research through the collection of longitudinal liquid biopsy specimens and tissues from patients with advanced cancer receiving standard of care therapy.

Aberrant DNA methylation is a promising biomarker for early cancer, multicancer, and types of cancer detection. However, there is currently a lack of reliable and quantifiable methods for DNA methylation analysis. In collaboration with our stakeholders, including NCI/EDRN, we have developed both genomic and cell-free format-based reference materials (RMs) for DNA methylation measurements. I will discuss the development, characterization, and utility of these RMs through pilot interlaboratory studies, as well as the improved control assay panel, aimed at standardizing DNA methylation measurements.

This session will explore how researchers can utilize the All of Us Research Program's participant cohort and comprehensive biospecimen repository to identify novel liquid biomarkers for early cancer detection, including circulating tumor DNA, proteins, and metabolites. Participants will learn strategies for integrating multi-omics data with electronic health records and social determinants of health to enhance biomarker discovery while ensuring equitable representation across populations.

Our experience testing ctDNA from the plasma of ~2300 patients with rare or uncommon cancers screened for the NCI-MATCH trial, the largest precision medicine initiative ever conducted, will be presented. We used a 523-gene targeted panel to identify tumor and CHIP-derived somatic alterations in blood and evaluated blood TMB and MSI status. CtDNA molecular profiles were also compared to targeted NGS data from matched tumor biopsies.

Liquid biopsy helped democratize genomically-targeted precision oncology; however, this is only the beginning of the impact for liquid biopsy in the treatment of cancer. In this session, we will explore how Infinity, a single combined genomic-epigenomic liquid biopsy technology, unlocks molecular phenotyping as the next evolution in therapy selection, molecular disease monitoring for more precise management of early and late-stage patients alike, and patient-centric early cancer detection.

Circulating tumor DNA (ctDNA) holds promise as a drug development tool to measure treatment efficacy in clinical trials. The ctMoniTR Project is a multi-stakeholder partnership used to develop the necessary data to support the use of ctDNA as a molecular response measure. Initial analyses across numerous clinical trials will evaluate the extent to which ctDNA change correlates with treatment outcomes. Validating the use of ctDNA as an early endpoint will accelerate research by enabling rapid identification of effective new cancer therapies and ultimately allow them to reach patients sooner.

Liquid biopsy is a highly attractive market and is largely composed of players that provide the ability to capture and analyze circulating tumor DNA (ctDNA). The new battle however, is going to be fought on the ability to detect cancer proteins, RNA as well DNA from blood; i.e., the emergence of multiomics in liquid biopsies.  A fundamental shift in pharma pipeline to protein-directed therapies is causing this change. My presentation will discuss this shift as well as the emergence of Cell Biopsies and Exosomes that will drive this next-generation of liquid biopsies.