VALPRAXIN

In 2008 colorectal cancer was the cancer type with highest incidence in the EU, accounting for 333,000 new cases and 148,000 deaths. Most CRC patients will receive chemotherapeutic treatment at some point during the course of their disease. The vast majority of these patients will be treated with the Topoisomerase I inhibitor irinotecan either in first or second line. However, less than 30% of the patients show an objective response, and it is currently not possible to distinguish responders from resistant patients. Using a cohort of 135 irinotecan-treated CRC patients we have previously identified Aprataxin (forkhead-associated domain histidine triad-like protein) as a new biomarker of response to irinotecan in advanced colorectal cancer (Dopeso et al Clin Cancer Res. 2010 16:2375- 82). Patients with low Aprataxin had longer progression-free (9.2 vs. 5.5 months; p=0.03) and overall survival (36.7 vs. 19.0 months; p=0.008) than patients with high tumor Aprataxin. In this project, we will rigorously validate Aprataxin as a biomarker of response to irinotecan-based treatment. For this purpose we will generate new analytical tools to assess mRNA and protein levels in a series of >3,800 colorectal tumors from patients treated with irinotecan for stage II, III and IV colorectal cancer from population-based and trial-based cohorts. Complete follow up data (>5 or >3 years for stage II-III and IV patients, respectively) will be collected and the predictive power of Aprataxin levels will be assessed. This biomarker will allow for the first time rational decisions on the use of irinotecan for the treatment of colorectal cancer, and should result in reduced unnecessary toxicity, increased survival rates and significant savings for the Health System of EU member states.

The aim of the project is to rigorously validate Aprataxin as a biomarker of response to irinotecan-based treatment. For this purpose we will generate new analytical tools to assess mRNA and protein levels in a target series of >3,000 colorectal tumors from patients treated with irinotecan for stage II, III and IV colorectal cancer from population-based and trial-based cohorts. Complete follow up data (>5 or >3 years for stage II-III and IV patients, respectively) will be collected and the predictive power of Aprataxin levels will be assessed. This biomarker will allow for the first time rational decisions on the use of irinotecan for the treatment of colorectal cancer, and should result in reduced unnecessary toxicity, increased survival rates and significant savings for the Health System of EU member states.