Liquid Biopsy Testing Platform Offers Unprecedented Sensitivity for MRD Detection

Current liquid biopsy assays are able to detect circulating tumor DNA (ctDNA) levels when tumor burden is high, but are not sensitive enough to detect minimal residual disease (MRD) when ctDNA levels are low. A significant portion of lymphoma patients eventually experience disease progression, and existing ctDNA assays fail to detect MRD in the majority of patients who will later relapse. Now, a novel liquid biopsy testing platform allows detection of MRD with up to a 100-fold improvement in sensitivity over existing assays.

Foresight Diagnostics, Inc.’s (Aurora, CO, USA) MRD platform is based on the Phased variant Enrichment and Detection by Sequencing (PhasED-Seq) technology. PhasED-Seq lowers the error profile of mutation detection in sequencing data by requiring the concordant detection of two separate non-reference events in an individual DNA molecule. By detecting more than one mutation, PhasED-Seq can more accurately distinguish tumor-derived cell free DNA (i.e., ctDNA) from healthy cell free DNA – enabling detection of ctDNA at levels below one part-per-million (<0.0001%). PhasED-Seq has been extensively validated in thousands of patient samples.

Image: The PhasED-Seq MRD testing platform with increased sensitivity could dramatically improve patient outcomes (Photo courtesy of Foresight Diagnostics)

Foresight has been granted a patent by the U.S. Patent and Trademark Office (USPTO) or the detection of MRD using its personalized phased variant detection platform. The granted patent covers Foresight's PhasED-Seq technology and the workflow behind the Foresight Solid Tumor Recurrence Test, an assay used to detect MRD from the plasma of cancer patients using DNA sequencing. The test is custom designed for each patient to track phased variants identified from tumor tissue samples using whole genome sequencing. The test offers unprecedented sensitivity for MRD detection, enabling a limit of detection below one part per million.

"Ultra-sensitive MRD tests are essential to detect residual disease and recurrence following completion of curative intent therapies," said Dr. Ash Alizadeh, MD/PhD, co-founder and Chief Medical Advisor at Foresight. "PhasED-Seq has been used in more than 20 different clinical studies, and can predict cancer relapse when tumor burden is low and patients are more likely to favorably respond to anti-tumor therapy. Sensitivity for MRD detection is important for all types of cancer and is particularly critical for cancers that shed relatively small amounts of circulating tumor DNA (ctDNA) into the bloodstream such as lung and breast cancer."

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Foresight Diagnostics, Inc.