Colorectal cancer belongs to the most prevalent cancers. The clinical management of colorectal cancer and simultaneous loss of quality life of patients and their disability on the job market represent important socio-economic burden. Every small improvement of the treatment efficacy and prolongation of patients’ lives will significantly help the healthcare systems, global economy and general wellbeing. This task may be achieved by a number of different routes, e.g., accelerated discovery of biomarkers for prognostication of the disease aggressiveness and prediction of optimal therapeutic approach with a high ratio of therapeutic benefit to adverse effects, in other words for individualized therapy and improved quality of life of patients. Our laboratories (Laboratory of Pharmacogenomics and Laboratory of Cancer Treatment and Tissue Regeneration) recently became members of International consortium TRANSCOLONCAN supported by EU project INTER-COST (Action CA17118). This project is aimed at complex characterization of colorectal cancer by help of state-of-the-art molecular biology approaches including pharmacogenomic profiling of patients.
Major aim of this project, funded by MŠMT, is to provide first Czech database of genetic variants connected with clinical outcome of individual colorectal cancer patient. In the discovery phase, whole exome sequencing (WES) will be performed in germline and somatic DNA pairs of 100 patients using NGS method. Authors will follow relevance of germline and somatic variability for prognosis and response of patients to therapy. Clinically validated bioinformatics tool for utilization of pharmacogenomic variants will be developed. Common germline variants and somatic alterations associating with patients’ prognosis and response will be further explored in the validation phase on prospectively collected blood DNA samples of large number of Czech colorectal cancer patients and later also on other relevant patient cohorts available from Action partners. Resulting, clinically validated, biomarkers (genes and variants associating with prognosis and therapy outcome of patients) will then be functionally characterized by Action partners. Both technological and bioinformatics parts of the project will be harmonized with other members of COST Action and pending collaborations, e.g., with Dr. David Hughes, and newly established ones, will be utilized for expedited generation of robust results and minimizing of the risk of project’s failure. The unique and well documented long-term collaboration between academics and clinicians in Biomedical Center Pilsen is prerequisite for achieving this goal.
Results of this project will be communicated with partners of the Action and then published in peer-reviewed journals with impact factor and presented at domestic and international meetings in order to inform scientific, clinical and pharmaceutical community worldwide.