Trends in Liquid Biopsy Tests

Oncologists have developed minimally invasive diagnostic platforms that use blood samples to detect clinically actionable biomarkers. Read about the latest trends in this Frost & Sullivan analysis.

Cancer patients have traditionally had to endure invasive techniques that typically comprise the use of biopsy guns, needles and forceps, and endoscopic devices often controlled by robotic biopsy guidance systems. More recently, oncologists have developed minimally invasive diagnostic platforms that use blood samples to detect clinically actionable biomarkers including circulating tumor (ct)DNA, exosomes,  circulating tumor cells (CTCs) and extracellular vesicles (EVs).

Today, biopsy techniques take the noninvasive approach a step further by using body fluids such as urine in order to assess disease biomarkers.  

ctDNA: The Preferred Target

Frost & Sullivan research indicates that ctDNA is becoming the preferred noninvasive method for several cancer profiling and treatment monitoring applications. This is driven by swift technological advances and the reduced cost of DNA sequencing, and is borne out by the patent landscape, with China leading the number of patents filed for ctDNA technologies. Second is the United States, followed by European countries. Leading ctDNA developers include Natera Inc. of San Carlos, Calif., and Verinata Inc. of Redwood City, Calif., which was acquired by Illumina in 2013. There is interest in developing ctDNA techniques for prenatal testing: LifeCodexx AG of Konstanz, Germany, holds patents in this area.

Cancer Genetics Inc. (CGI) of Rutherford, N.J., is an innovative developer of ctDNA-based liquid biopsy testing for solid and hematological malignancies. CGI’s multidisciplinary approach encompasses flow cytometry, immunohistochemistry, fluorescent in situ hybridization, microarray-based comparative genomic hybridization and next-generation sequencing platforms for patient profiling.

CGI’s Liquid::Lung-cfDNA technology platform is Clinical Laboratory Improvement Amendments (CLIA)-certified by the U.S. Food and Drug Administration (FDA) and is being investigated for use in detecting indications of colorectal, breast and kidney cancers. This year, CGI announced that it formed a partnership with Ventana Medical Systems, a member of the Roche Group, to enhance patient access to the VENTANA PD-L1 (SP263) Assay, also approved by the FDA.

CGI is leveraging its liquid biopsy expertise in ongoing research collaborations with oncologists and cancer centers to find new solutions for kidney cancer, leukemia, non-Hodgkin’s lymphoma, and HPV-associated cancers. Among CGI’s partners are the Cleveland Clinic, the Mayo Clinic, Memorial Sloan Kettering Cancer Center, the National Cancer Institute, Beth Israel Deaconess Medical Center, the University of Iowa Cancer Center, and Columbia University.

MDxHealth in Herstal, Belgium, has developed a methylation-specific polymerase chain reaction (MS-PCR) liquid biopsy technology to provide a sensitive quantitation of methylated cancer genes, and a quantitative reverse transcription PCR (RTqPCR) platform that is used for urine mRNA analysis. The RTqPCR technology can be used to diagnose and manage prostate and urological cancers. The company also has formed a partnership with Burlington, N.C.-based Laboratory Corporation of America to distribute PredictMDx for glioblastoma.


Preventing CTCs from Metastasizing

Because CTCs are the cells that metastasize from a tumor into the circulatory system, it is essential to identify them as soon as possible. CTC biomarkers are detected by cytometry, imaging and immunoassay of blood samples, but at least one company—CellSearch of San Diego, Calif.—has developed an FDA-approved liquid biopsy technology to better manage colorectal, prostate and metastatic breast cancers. Indeed, the China FDA has also approved the CellSearch CTC test for metastatic breast cancer. The potential of this technology likely led Menarini-Silicon Biosystems S.p.A. of Bologna, Italy, to acquire CellSearch in 2016.

Hybrid ctDNA and CTC Target Selector

A novel approach by Biocept Inc., a molecular diagnostic firm also based in San Diego, combines ctDNA and CTC-based liquid biopsy assays in its proprietary Target Selector platform to analyze cancer markers in blood samples. This provides physicians with clinically actionable insights for enhanced treatment and monitoring of melanoma and breast, colon, gastric and prostate cancers. Biocept has collaborated with leading academic institutions such as the University of Minnesota and Yale University, as well as the Dana-Farber Cancer Institute in Boston, to validate its testing.

Finding Clues in EVs

EVs include the apoptotic vesicles, ectosomes, microvesicles, microparticles, oncosomes and exosomes that are secreted by living cells. Evaluating the biomarkers in EVs can help to profile and monitor the treatment of cancers.

As its name implies, Exosome Diagnostics Inc. of Waltham, Mass., has developed an exosome-based liquid biopsy platform called ExoLution, and a point-of-care instrument, Shaky, that captures protein for analysis. Both technologies assess RNA, DNA and proteins in biofluids to raise the sensitivity of the assay.

A partnership between the Atlantic Cancer Research Institute in Moncton, New Brunswick, Canada, and New England Peptide in Gardner, Mass., created Excipio Technologies of Moncton in 2013 to commercialize the patented Vn96 EV isolation technology that employs the high selectivity of the Vn96 peptide for heat shock proteins that are present on the surface of exosomes and EVs. This allows EVs to be analyzed for pathological biomarkers associated with cancers.

The Road Ahead

The pursuit of earlier cancer detection and patient demand for less-invasive procedures are driving all liquid biopsy developments. Researchers are showing more interest in epigenetics, which is supporting the development of ctDNA technologies in cancer diagnosis and management. Using CTC- and EV-based diagnostics for disease profiling and treatment monitoring will spark more innovations in these areas.

Pharmaceutical and biotechnology companies will collaborate to combine highly sensitive liquid biopsy analysis techniques with diagnostic platforms. If they can meet the twin needs for accuracy and patient comfort, these solutions could disrupt cancer detection and treatment directly, and strengthen the development of liquid biopsy in other diagnostic applications as well.

Copyright © 2017 Frost & Sullivan