17 March 2023 - - Barcelona-based biotechnology start-up Reveal Genomics, S.L., which seeks to advance precision oncology through biomarker innovation, has announced 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.

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 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.

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 USD 4.3bn in 2022 and a projected growth rate of 18.3%, reaching USD 10.0 bn 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.

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 advanced techniques, 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, and the Vall d'Hebrón Institute of Oncology.