Project description DEENESFRITPL Circulating tumour DNA as therapeutic response biomarker Drugs that inhibit major angiogenic pathways belong to several new anticancer treatment options. Efficient treatment needs accessible biomarkers to control the response to anti-angiogenic therapies. Recent studies discovered that tumour hypoxia causes DNA hypermethylation, and these changes lead to resistance to anti-angiogenic treatment. The EU-funded INITIATOR project aims to validate the hypothesis that methylation patterns detectable in the circulating free DNA (cfDNA) in the plasma of patients with metastatic colorectal cancer can be used to predict early response to anti-angiogenic therapies using a specifically developed cfDNA co-methylation test. The new approach might overcome many of the issues that are currently associated with anti-angiogenic drugs as the cfDNA is readily accessible and can be sampled during initial and follow-up treatment. Show the project objective Hide the project objective Objective Tumors are characterized by a disorganized vasculature, leading to profound levels of hypoxia. Normalizing the blood vessel formation (angiogenesis) in tumors has therefore become an attractive therapeutic strategy, leading to the development of approved drugs that inhibit major angiogenic pathways. Resistance however restricts the success of these anti-angiogenic drugs in some patients. There is thus a great clinical need for readily accessible markers that serve as reliably predictive biomarkers of anti-angiogenic therapies. However, all markers discovered to date have a limited predictive power. In the ERC Consolidator Grant CHAMELEON, we discovered how tumor hypoxia causes DNA hypermethylation and how changes in DNA methylation underlie resistance to anti-angiogenesis. Here, we propose to validate how methylation patterns detectable in plasma circulating free DNA from a prospective collection of patients with metastatic colorectal cancer can be used to predict an early response to anti-angiogenic therapies by using our in-house developed cfDNA co-methylation test, referred as the ‘INITIATOR’ test. If successful, we anticipate that this project will overcome many of the issues that are currently associated with anti-angiogenic drugs: cfDNA is readily accessible and can be serially sampled during treatment or follow-up, cfDNA also mirrors the entire tumor and not just the biopsied site, while the epigenetic changes detectable in cfDNA may be a dynamic representation of the tumor in response to treatment. Fields of science natural sciencesbiological sciencesgeneticsDNAmedical and health sciencesclinical medicineoncologycolorectal cancernatural sciencesbiological sciencesgeneticsepigenetics Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2019-POC - ERC Proof of Concept Grant Call for proposal ERC-2019-PoC See other projects for this call Funding Scheme ERC-POC-LS - ERC Proof of Concept Lump Sum Pilot Host institution VIB VZW Net EU contribution € 150 000,00 Address SUZANNE TASSIERSTRAAT 1 9052 ZWIJNAARDE - GENT Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all VIB VZW Belgium Net EU contribution € 150 000,00 Address SUZANNE TASSIERSTRAAT 1 9052 ZWIJNAARDE - GENT See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Research Organisations Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost No data
