REVEAL GENOMICS®´ breakthrough technology enters the liquid biopsy field in Oncology

March 9, 2023

· REVEAL GENOMICS®´ machine learning-based technology applied to ctDNA was able to predict drug response and survival outcome in patients with metastatic breast cancer treated with endocrine therapy and CDK4/6 inhibitors.

· This new approach provides multi-feature genomic predictors from ctDNA for breast cancer and other types of cancer.

· The assay allows opportunities for discovering new cancer-associated phenotypes and the ability to detect these clinically relevant tumor phenotypes using ctDNA.

Barcelona, Spain. REVEAL GENOMICS, S.L., a Barcelona-based biotechnology start-up seeking to revolutionize precision oncology through biomarker innovation, announced today a new addition to its pipeline consisting of a novel biomarker approach in liquid biopsy for patients with advanced cancer. The main findings of this development were published in Nature Communications this month, in collaboration with several academic institutions, including the Hospital Clinic/IDIBAPS de Barcelona (Spain), University of Barcelona (Spain), Vall d'Hebrón Institute of Oncology (Barcelona, Spain), Hospital Universitario 12 de Octubre (Madrid, Spain), the Catalan Institute of Oncology (Badalona, Spain), and the University of North Carolina (Chapel Hill, USA).

Analysis of cell-free  DNA (cfDNA), present in body fluids such as plasma, is broadly known as liquid biopsy. In oncological patients, cfDNA contains a fraction of tumor-derived genomic material (ctDNA), that has been proven as a valuable resource to identify tumor-borne genetic alterations. However, cancer is highly complex, and additional biological information is needed to refine the prediction of patient outcome and/or benefit from treatment.

Dr. Aleix Prat, Co-Founder and CSO of REVEAL GENOMICS® and the lead author of the study, explained: “Our proprietary and novel supervised learning computational approach predicts complex tumor features including gene expression, protein and tumor histology using one data source: DNA sequencing. Here, we demonstrate that our approach is feasible in plasma cfDNA and that it provides clinically relevant information.

New product in the pipeline

Single DNA alterations in metastatic breast cancer, such as ESR1 or PIK3CA mutations, are valuable information but are not enough to predict the patient outcome. To address this issue, investigators from REVEAL GENOMICS® sequenced cfDNA from 459 patients with metastatic breast cancer, including 245 patients with hormone receptor-positive/HER2-negative (HR+/HER2-) treated with endocrine therapy and a CDK4/6 inhibitor (i.e., palbociclib, ribociclib or abemaciclib).

Firstly, REVEAL GENOMICS®' proprietary machine-learning multi-gene signatures were applied in plasma and linked to DNA/RNA/protein data from tumor tissue (paired samples). The results showed, for the first time, that multi-gene signatures tracking complex biological features can be successfully identified in ctDNA. These complex biological features include, among others, measures of tumor proliferation and estrogen receptor signaling, similar to what is accomplished using direct tumor tissue DNA or RNA profiling. For example, one of REVEAL GENOMICS®´ signatures in plasma ctDNA, known as the estrogen receptor (ER) signaling signature, predicted the ER status of the tumor tissue as determined by standard immunohistochemistry.

Secondly, the authors discovered that the combination of 150 biologically relevant signatures identified 4 new DNA-based molecular subtypes of breast cancer. More importantly, these 4 biological entities were strongly associated with survival outcome in patients with early-stage and/or metastatic HR+/HER2- breast cancer.

Finally, the investigators focused on a particular genomic signature called retinoblastoma loss-of-heterozygosity (RB-LOH), which was designed to capture tumor biological status induced by the loss of RB - a known key player in tumor cell division needed for CDK4/6 inhibitors to work. In patients with metastatic HR+/HER2- breast cancer treated with endocrine therapy and a CDK4/6 inhibitor, REVEAL GENOMICS®' ctDNA RB-LOH signature identified the 20-30% of patients who do not respond well to this treatment.

Dr. Ana Vivancos, Co-Founder and consultant of REVEAL GENOMICS®, concluded: “Our novel approach can have huge implications in the clinical setting, and opens new opportunities for the discovery of multi-feature genomic predictors coming from ctDNA in breast cancer and other types of cancer.

About liquid biopsy

The liquid biopsy market in oncology can potentially become the future gold standard, considering its various advantages over conventional cancer diagnostic approaches. The global market boasts a total value of $4.3 billion in 2022 and a projected growth rate of 18.3%, reaching $10.0 billion by 2027. The market is driven by the rising incidence and prevalence of cancer in the developing world and the increasing preference for noninvasive treatment procedures.

Dr. Patricia Villagrasa, Co-Founder and CEO of REVEAL GENOMICS®, concluded: “Our company is committed to creating and developing novel genomic-based assays in oncology and demonstrating their clinical utility as we have already done with our first product, the HER2DX®, which is already impacting patient care in early-stage HER2-positive breast cancer. This new ctDNA-based assay, called DNADX, is our second product expected to be available in 2024." The Spanish Ministry of Science and Innovation has granted funding for this new product, validating DNADX as an innovative and clinically useful tool.


REVEAL GENOMICS, S.L. is a biotechnology start-up developing innovative diagnostic tools to help define the best therapeutic strategy for patients with cancer. The company uses pioneering techniques, sophisticated computer applications, and machine learning to generate new cancer research data and develop biomarkers of straightforward clinical utility.

REVEAL GENOMICS, S.L. is a spin-off company of the Hospital Clínic de Barcelona, IDIBAPS, the University of Barcelona (U.B.), and the Vall d'Hebrón Institute of Oncology (VHIO).

REVEAL GENOMICS® and HER2DX® are registered trademarks of REVEAL GENOMICS, S.L.

Website: Twitter: @revealgenomics

Further information: Adriana Herrera,