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In the genes: OncoDNA
Targeted therapies are one of the most recent advances in cancer treatment, and a major focus of current cancer research. Unlike chemotherapy drugs, which are toxic to normal cells and often cause debilitating side effects, targeted drugs identify and attack cancer cells more precisely, usually with little damage to normal cells.
But finding the right drug, or the right combination of drugs, to treat a cancer effectively is a tricky business.
Cancers occur because of abnormalities in the body’s DNA – deoxyribonucleic acid, the chemical that contains the genetic instructions that all living organisms, and many viruses, use to develop and function. These instructions are organised into sequences called genes. Throughout life, we are exposed to physical or chemical agents that change the DNA within the cells of the body, causing them to mutate. When the frequency of mutations reaches above certain normal levels, it leads to cancer.
Classical methods to find mutations are slow and not always accurate, according to Jean-Pol Detiffe, an industrial pharmacist and the founder and CEO of new Belgian company OncoDNA. “Cancers move fast. You need fast and effective treatment to stand a good chance of recovery, so the right treatment must also be fast and available,” he says.
With medical pathologist Pierre Lefesvre, medical director at OncoDNA, Detiffe has developed a series of tests which identify those mutations known to respond to targeted therapies that already exist in Europe, or to therapies that are in the final stages of development.
The first test, OncoDEEP DX, compares the DNA in a tiny sample of a patient’s tumour tissue with that of their healthy tissue to identify treatable mutations in 40 genes. It was validated in Belgium in November last year, gained competence and quality accreditation and is already being used by hospitals in Wallonia and Luxembourg. Orders for the test from other parts of Europe are now also beginning to come in, says Detiffe. The lab work is done using powerful DNA sequencing technology by partners at the Institute of Pathology and Genetics (IPG) in Gosselies, on the outskirts of Charleroi, to which the company is affiliated and from which it span off last year. The microscopic threads of DNA are harvested by scientists and read by sophisticated Ion Proton sequencing machines developed by Life Technologies, a global biotechnology tools company. OncoDNA then looks for specific mutations and presents the results to oncologists with the corresponding treatments available.
The whole process takes a maximum of 10 days and is on the market for €750. The test was expected to be approved for partial reimbursement from social security funds by the government at the time of going to press. “This was impossible a year or two ago because it was still so expensive,” says Detiffe. “Now we can offer it as a mainstream medical test.”
When researchers first mapped a human genome in 2003, the effort cost just over €2bn . The cost of analysing someone’s whole genetic code is now down to a few thousand euros with the development of ever more powerful and accurate technologies. “The IPG is the first place in Belgium to get the Proton sequencing machine, and the second in Europe,” says Detiffe.
If the company doesn’t find a mutation with a corresponding therapy, it deploys OncoDEEP Clinical, a second, larger test which looks for mutations and rearrangements in 400 genes linked to the development of therapies undergoing clinical trials. This test also takes a maximum of 10 days to complete. Results are presented in a web-based electronic report and include data from histological pathology reports, the sequencing data, a list of available drugs that the data indicates would be effective and not effective, and information about clinical trials for which the patient is eligible. If both the tests fail to deliver, the company can also offer more in-depth sequencing of the exome – all the coding part of genes that do a particular coding job.
Another product line in development by the company is the project OncoTRACE. It is the first personalised biomarker product which can monitor a patient’s cancer with high sensitivity and also give early response indicators to the treatment choice. By analysing the mutations or rearrangements in the DNA of a patient’s tumour, the test provides a personalised kit of blood biomarkers. This offers extremely specific analysis, says Detiffe. “With this technique we can also use classical techniques to develop blood tests to measure the amount of tumour DNA circulating in the blood, so we can tell how well a cancer is responding after three weeks of treatment or if there is a recurrence. We can detect a recurrence of cancer up to six months earlier than with imaging techniques, which only detect tumours when they are around 5mm in size.”
The OncoTrace test is currently only available to researchers and costs around €3,000. In January, the company received €1.4m of funding from the Walloon government for a two-year study to clinically validate the technique using a large number of patients. “The validation study will be conducted with 250 patients at large cancer centres all over Europe,” says Detiffe. He aims to include around 20 to 25 patients from 10 collaborating centres, in Belgium, France, Germany, Scandinavia, Italy, Spain, Switzerland and the UK.
To develop all these activities, the company has raised €2m from public and private investors. Among its investors are venture capital firm Sambrinvest; Jean Stephenne, former president of GlaxoSmithKline Vaccines; and François Blondel, former CEO of medical device company IBT.