Restoring the blood vessel network using anti-angiogenic therapy in tumors has become an attractive strategy to fight cancer. The Translational Genetics lab headed by Prof. Diether Lambrechts previously discovered how changes in DNA methylation patterns underlie resistance to anti-angiogenesis in cancer. However, there is still a great clinical need for readily accessible markers that serve as reliably predictive biomarkers of anti-angiogenic therapies. Therefore, in this ERC Proof-of-Concept project the lab has investigated how DNA methylation patterns detectable in plasma cell-free DNA (cfDNA) from patients with metastatic colorectal cancer (mCRC) can be used to predict an early response to the anti-angiogenic therapy Avastin by using an in-house developed next generation sequencing-based methylation test, referred as the ‘INITIATOR’ test. Using this assay, they found that patients showing large methylation changes in specific genomic regions during treatment have a longer overall survival time when compared to patients where only a small reduction in methylation levels occurred. This research demonstrates that the epigenetic changes detectable in blood-derived cfDNA may be a dynamic representation of the tumor in response to treatment and confirms that the ‘INITIATOR’ test may be a potential readily accessible blood-derived marker for prediction and monitoring the response to anti-angiogenic treatment in cancer treatment. Clinical application of this blood-derived test will transform the way in which mCRC patients are treated by rapidly directing patients with resistance to Avastin towards alternative therapies, thus sparing them from Avastin related morbidities.
