CORDIS - EU research results
CORDIS

CIRCULATING TUMOR DNA AS AN EPIGENETIC BIOMARKER FOR TUMOR RESPONSE

Project description

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.

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.

Host institution

VIB VZW
Net EU contribution
€ 150 000,00
Address
SUZANNE TASSIERSTRAAT 1
9052 ZWIJNAARDE - GENT
Belgium

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Region
Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent
Activity type
Research Organisations
Links
Total cost
No data

Beneficiaries (1)