NEW YORK – A new European effort aims to develop and eventually deliver to market a new multiplex test for the early diagnosis of colorectal cancer. The project, called Dioptra, commenced earlier this year with a budget of €13 million ($14 million) and will run through December 2026. It involves 28 public and private partners from 15 European countries.
Investigators from the National Technical University of Athens in Greece are coordinating Dioptra. The envisioned test will involve measuring protein biomarkers in samples obtained by liquid biopsy, as well as artificial intelligence-based analysis tools.
The ultimate goal is to develop a tool that can be used in screening programs to identify individuals who otherwise would not qualify for screening according to current guidelines, such as those who fall into younger age groups but are at high risk for developing the disease.
A mobile application is also planned that will offer healthy individuals the ability to monitor their risk over time of developing cancer based on their test results, as well as other risk factors.
Protavio, an Athens-based biotechnology company with expertise in developing and commercializing CE-IVD-marked multiplex panels, is taking part in the Dioptra project.
Christos Fotis, Protavio's research and innovation officer, said in an interview that the company, which also has offices in the UK, intends to use its know-how to help in the discovery of blood-based biomarkers for the test by comparing the blood and tissue samples from individuals with early-stage cancer with samples from healthy controls.
Fotis said that the Dioptra consortium will use "state-of-the-art proteomic and transcriptomic technologies" to analyze the protein and RNA signatures of colorectal cancer samples, to "verify the connection of blood-based biomarkers to the colorectal cancer mechanism," and to prioritize markers directly related to the disease.
In terms of transcriptomic technologies, Protavio will mainly perform RNA sequencing using an Illumina workflow, he said.
According to Fotis, about 150 matched blood and tissue samples from the Medical University of Graz's biobank, as well as the National and Kapodistrian University of Athens and the Saint Savvas Genetic Anticancer Oncology Hospital of Athens, will be used in a retrospective study for the purpose of marker selection. This will be followed by a prospective study of the Dioptra test and analysis system across eight clinical sites in the EU, relying on blood samples obtained from about 1,200 participants.
Protavio will also help seek out potential partners that might wish to license or commercialize the panel and will aid in the regulatory approval of the assay, plus work to craft a business plan and a pricing strategy that "reflects the value" of the biomarker panel and its benefits to patients and healthcare providers.
Protavio has developed and launched tests in a variety of formats, including for use on the Luminex platform, enzyme-linked immunosorbent assays (ELISA), and lateral flow tests. Its quality management systems, Fotis noted, are compliant with the ISO 13485 standard as well as the EU's new In Vitro Diagnostic Regulation. Fotis said the firm has been involved in more than 150 biomarker development projects and has produced multiplex proteomic assays for other research consortia, where AI-based methods were similarly used to select the "optimal combination of biomarkers that maximize diagnostic performance."
In one of these projects, called Oncologics, Protavio developed multiplex proteomic assays for patient stratification and personalized applications. In another, dubbed SymBioSys, the company helped to validate a multiomics biomarker discovery platform that combined multiplex experimental methods and network-based computational approaches, Fotis said.
For Dioptra, it is not yet clear what form the test will take. Fotis said several platforms could be used in the development of the test, including ELISAs, as well as those sold by Luminex, now part of DiaSorin, and Uppsala, Sweden-based Olink. Technology selection will depend on the size of the marker panel. "If the optimal set of biomarkers is composed of a low number of proteins," Fotis said, "we will evaluate the feasibility of developing and producing a multiplex lateral flow device."
George Matsopoulos, an associate professor at the National Technical University of Athens, is leading Dioptra. He said separately that the project will start out with a large pool of about 3,000 candidate biomarkers to identify a "discriminative subset" for precancerous and initial colorectal cancers. These will undergo further assessment followed by the pilot-based validation.
Matsopoulos said that in addition to using proteomics, genomics, and artificial intelligence to develop its screening tool, the project will integrate other data, such as medical and behavioral data, into its risk assessment.
Another goal is to be able to link the outcome from the screening tool with recommendations on how to change one's personal behavior to lessen the risk of developing colorectal cancer. These could be made available via a mobile application.
Ioannis Papanikolaou, a professor of gastroenterology at NKUA, said that there is a need for an early-stage screening test that can be made available to a wider swath of the population.
"As participation of the general public in colonoscopy screening is relatively low, and whereas colorectal cancer is one of the most frequent cancers, there is a need to find markers that could motivate those with a high likelihood of having advanced adenomas or colorectal cancer to undertake a colonoscopy," Papanikolaou said. This would allow the removal of any adenomas or the diagnosis of cancer at an earlier and curable stage.
Papanikolaou added that making the screening service available in a mobile app format could also help reach more persons under the age of 50 who could be at higher risk of developing cancer. Most screening programs currently start at age 50, he noted.
It's a need that multiple other players are striving to address. For example, Guardant Health, a Palo Alto, California-based company, has developed a blood-based colorectal cancer detection assay called Guardant Shield, and last month said that it submitted the final module of a submission for premarket authorization to the FDA. Also last month, CanSense, a Swansea, Wales-based company, announced that it had raised £1.5 million ($1.7 million) to support the development of a blood-based test for colorectal cancer detection.
Also, Exact Sciences' stool-based Cologuard test was approved by the US Food and Drug Administration in 2014 as a screening test for colorectal cancer. The test is intended for individuals ages 45 and older with an average risk of colon cancer.
Tests such as the one being developed by Dioptra have faced challenges, however. Fotis noted that in the past, proteomic or genomic assays for advanced adenomas often had low sensitivity. "This is why we want to focus our efforts on protein biomarkers present in blood, that are connected to the mechanism of colorectal cancer initiation," he said.
But Fotis underscored the growing need for blood-based biomarker tests for colorectal cancer screening. He cited a 2021 decision by the US Centers for Medicare & Medicaid Services (CMS) to cover blood-based tests if certain requirements are met, including that the patient is between 50 and 85 years old, asymptomatic, and at average risk of developing colorectal cancer. Also, the tests must have proven sensitivity greater than or equal to 74 percent and specificity greater than or equal to 90 percent in the detection of colorectal cancer compared to colonoscopy, and have FDA market authorization. CMS in its decision recommended that testing be conducted in three-year intervals.
According to Protavio's Fotis, Europe would be the first market for any resulting test, should Dioptra be successful. Such a test, he noted, would "empower the EU's Mission on Cancer," a European effort to support cancer research, particularly through the EU's Horizon Europe funding program. Reaching the US market, added Fotis, would be a subsequent goal for the Dioptra test.