Aqtual, Inc., a precision medicine company developing active chromatin cell-free DNA (cfDNA) diagnostics for oncology and chronic disease, today announced new findings demonstrating its blood-based active chromatin cell-free DNA platform can simultaneously evaluate immune, stromal, and tumor-associated genomic biology from a single blood-based assay. These results highlight the potential of this approach to noninvasively monitoring dynamic changes in tumor microenvironment and emerging mechanisms of treatment resistance. The findings, led by investigators at UHN’s Princess Margaret Cancer Centre, were published in the peer-reviewed journal npj Precision Oncology[1] and will be extended with new longitudinal resistance analyses presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, held May 29 – June 2 in Chicago.
In the published study, a cohort of 30 patients with advanced leiomyosarcoma treated with durvalumab-based combination therapy showed baseline plasma active chromatin cfDNA signatures associated with clinical benefit. The platform identified biological features associated with clinical benefit across three categories of signal derived from a single blood sample:
- Immune-associated programs, including B-cell and T-cell activation signatures, were associated with improved progression-free survival (HR 4.07 and HR 4.27, respectively; both p<0.01)
- Stromal remodeling signatures associated with extracellular matrix organization were linked to resistance and shorter progression-free survival (HR 0.17, p<0.001)
- Tumor-associated genomic features, including copy number variation and tumor fraction (>5% threshold; HR 3.33, p=0.008), also correlated with clinical outcome
- Plasma-derived promoter activity showed strong agreement with matched tumor RNA sequencing, with a correlation of 0.81, suggesting that the blood-derived signal reflects the same underlying transcriptional programs observed in tissue.
“There is an important need for predictive biomarkers that may help identify which patients with leiomyosarcoma are most likely to benefit from immunotherapy approaches,” said Dr. Albiruni Abdul Razak, MB MRCPI, Clinician Investigator, UHN’s Princess Margaret Cancer Centre. “This study provides preliminary evidence that a simple blood test taken before treatment may help identify which patients could benefit from combination immunotherapy approaches.”
New analysis presented at ASCO extends these findings by examining how these signals evolve under treatment pressure. Using paired baseline and progression samples from the same cohort, the study tracks longitudinal changes in immune, stromal, and tumor associated genomic features, including in patients who initially experienced clinical benefit but later progressed. The findings provide an early view into resistance biology in blood in a clinical setting where biopsies are often difficult or not feasible.
Leiomyosarcoma presents a challenging setting for liquid biopsy due to its relatively low tumor mutation burden, which can limit traditional ctDNA approaches. In advanced disease, obtaining tissue biopsies can also be difficult. Unlike traditional liquid biopsy methods that primarily focus on mutations or methylation patterns, active chromatin profiling may provide additional insights into tumor-associated immune and stromal biology while also supporting established genomic analyses, such as copy-number profiling.
“The significance of this work is not any single biomarker, but the architecture behind them,” said Diana Abdueva, PhD, Co-Founder and Chief Executive Officer of Aqtual. “Existing liquid biopsy platforms typically read tumor mutations, tissue origin, or fragmentation patterns independently. In a single library, our platform reads immune state, stromal state, and tumor genomics simultaneously, in a sarcoma setting where conventional ctDNA approaches often struggle and repeat tissue biopsies are rarely feasible. While these findings are highly encouraging, they were generated in a relatively small patient cohort and will need to be confirmed in larger, independent studies, which are already underway.”
ASCO Poster Details:
- “Identification of checkpoint inhibitor resistance mechanisms in leiomyosarcoma through enrichment of active chromatin-associated cell-free DNA.”
- Poster #335
- Monday, June 1, from 1:30-4:30 p.m. CDT
- Presented by: Carlos Diego Holanda Lopes, MD
For more information or to schedule a meeting with Aqtual during ASCO, please contact admin@aqtual.com or visit www.aqtual.com.
About Aqtual, Inc.
Aqtual, Inc. is a precision medicine company developing products for chronic disease management and oncology utilizing a novel cell-free DNA-based platform. Aqtual’s proprietary platform evaluates protein regulation, epigenetics, and transcriptomics solely using cell-free DNA fragments found in the blood. The platform yields efficient and robust real-time analysis of disease and treatment while overcoming the limitations of previous cell-free DNA methodologies.
[1] Lopes CDH, Wu HT, Dilger K, et al. npj Precision Oncology. 2026. doi:10.1038/s41698-026-01451-9
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