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Predictive Genomic Biomarkers Methods for Combination Bevacizumab (Avastin) Therapy in Metastatic Colorectal Cancer

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Anti-angiogenic therapy in colorectal cancer

Current treatment for metastatic colorectal cancer (mCRC) includes newly developed complex targeted therapeutics. European scientists united efforts to identify a new generation of biomarkers for stratification of patients receiving combination therapy.


Colorectal cancer is the third most commonly diagnosed cancer in males and the second in females in the developed world. Currently, an important treatment for these patients is the drug Avastin® (bevacizumab), which inhibits tumour blood vessel formation (angiogenesis) and thus prevents tumour growth. Up to now, the underlying genomic mechanisms that determine whether or not a patient will respond to Avastin® combination therapy have been unknown. Further, the treatment is not effective in all patients - which may result in some patients suffering related side effects, without benefit. The future use of Avastin® in mCRC (and other cancers) is likely to be greatly influenced by the availability of predictive biomarkers to allow selection of patients who will attain the greatest benefit. Up to now, there have been no biomarkers validated for avastin nor associated companion diagnostics. In the EC-funded project ANGIOPREDICT (Predictive genomic biomarkers methods for combination Bevacizumab (Avastin) therapy in metastatic colorectal cancer), academic cancer biologists and industry based biotechnology researchers have worked together with clinicians to explore biomarker strategies for the prediction of individual patient response to Avastin® combination therapy. The ultimate goal is to help develop diagnostic tests using these biomarkers, in order to provide clinicians with the means to predict patient treatment responses in the future. In the project ANGIOPREDICT partners used a number of different technologies to analyse tissue samples from patients receiving Avastin® combination therapy or chemotherapy, to explore potential predictive biomarkers. The results of this exploratory work was then validated using other tissue samples (e.g. from the ANGIOPREDICT clinical trial). Significant results from the work undertaken include: the identification of novel predictive Copy Number Alternation biomarker signatures; priority filing of a patent application (January 2016) to protect valuable methylation biomarkers for diagnostic and/or prognostic purposes in colon and other cancers; identification of novel predictive classifiers, confirmation of the predictive potential of recently published multi-gene signatures (molecular subtypes) and description of novel response prediction molecular clusters; new method to stratify ANGIOPREDICT patients into subtypes with significantly different survival outcomes; Application of an integrative statistical model over two data sets (CNA and somatic SNPs) to define two patient clusters with a significantly better treatment outcome. In light of the advances made, Angiopredict has opened up a number of promising new avenues for further research in this area. The project has achieved significant advances towards the ultimate goal of delivering biomarkers and diagnostic tests to predict response to Avastin® combination therapy. Ultimately the project will contribute to more focused treatment, better care and quality of life for patients and reduced healthcare costs.


Anti-angiogenic therapy, colorectal cancer, biomarkers, Bevacizumab, ANGIOPREDICT

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