Multiomic Blood Test Supports Noninvasive Monitoring and Subtyping in Pancreatic Cancer

Clinicians also have limited noninvasive tools for identifying resistance and molecular subtype. A new multiomic blood test combines 5-hydroxymethylcytosine (5hmC) signatures in cell-free DNA (cfDNA) with genomic and glycan features to support treatment monitoring and molecular subtyping.

ClearNote Health’s (San Diego, CA, USA) Avantect Pancreatic Cancer Test and its Virtuoso epigenomics platform will be featured with new data at the American Association for Cancer Research (AACR) Conference on Pancreatic Cancer, taking place September 25–28 in San Diego. The presentations focus on plasma cfDNA 5hmC and whole‑genome sequencing (WGS) profiling in BRCA‑positive pancreatic ductal adenocarcinoma. The work explores expanded utility for treatment monitoring and molecular subtyping.

The Avantect Pancreatic Cancer Test is a multiomic assay that integrates epigenomic 5hmC patterns, genomic features, and a glycan biomarker with optimized machine-learning algorithms to detect and evaluate biologically relevant cancer-associated signals from a blood sample. The test is intended for individuals with a known genetic predisposition or family history of pancreatic cancer, as well as those age 50 or older who have been newly diagnosed with type 2 diabetes. It is currently being used in several large, ongoing studies focused on populations at elevated risk for pancreatic cancer.

The test was developed and its performance characteristics established by a CLIA-certified laboratory qualified to perform high-complexity testing, but it has not been cleared or approved by the U.S. Food and Drug Administration (FDA). Avantect is included in the Surveillance of pAncreatic health aFter diabEtes Diagnosis (SAFE-D) study led by the National Health Service (NHS) in the United Kingdom and is also being incorporated into the international Pancreatic Cancer Early Detection (PRECEDE) Consortium. Together, these initiatives are evaluating approaches to earlier diagnosis and risk-stratified screening in defined high-risk populations.

In collaboration with Sheba Medical Center and Tel Aviv University, investigators also analyzed 69 plasma samples to examine whether Avantect could provide insight into treatment response and tumor biology. Numeric Avantect scores, derived from 5hmC and WGS profiles, were associated with clinical response, acquired resistance, and refractory disease in patients receiving platinum-based chemotherapy or PARP inhibitors. 

In addition, cfDNA 5hmC signals largely corresponded with tumor subtypes identified through patient-derived xenograft expression profiling, suggesting that plasma-based analysis may capture both cancer burden and molecular subtype. The findings will be presented in scientific poster B045, “Plasma cfDNA 5-Hydroxymethylcytosine Signatures Associate with Treatment Response and Molecular Subtype in BRCA-Mutant Pancreatic Cancer,” in Indigo CDCH on Sunday, September 27, at 9 a.m.

“Patients with BRCA-positive pancreatic cancer need better tools to monitor treatment response and emerging resistance application. Our findings suggest plasma 5hmC profiling may provide a noninvasive view of both treatment response and tumor subtype, supporting more personalized care in the future,” said Talia Golan, M.D., principal investigator of the study and head of the Sheba Pancreatic Cancer Center at Sheba Medical Center.

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