Biomarkers of Colorectal Cancer

Colorectal cancer (CRC) which affects over one million individuals annually [1] has recently seen an increased interest in identifying biomarkers and new treatment strategies. This has resulted in a significant rise in the median overall survival of CRC from 6 to 24 months [2]. Standard treatment for CRC has progressed from 5-fluroruracil monotherapy to combination chemotherapy (5-flurouracil and irinotecan and/or oxaliplatin) and more recently to biological agents targeted at angiogenesis and the epidermal growth factor receptor (EGFR). The monoclonal EGFR antibodies, cetuximab and panitumumab have been shown to be effective in 10-15% of metastatic CRC patients. Patients who do not benefit from cetuximab or panitumumab have a K-RAS mutation at codon12. However patients with a K-RAS mutation at codon 13 (i.e. G13D) do respond positively to EGFR antibody therapy. Therefore it is recommended that the mutational status of K-RAS should be assessed in every CRC patient prior to initiating treatment with EGFR antibodies [2]. Recent advances in multiplex genotyping technologies and high-throughput genomic profiling by next-generation technologies make possible the rapid and comprehensive analysis of the cancer genome of individual patients even from very little tumor biopsy material. Predictive biomarkers using molecular diagnostics are currently in use in clinical practice of CRC oncotherapy and are successfully being used to evaluate benefits that can be achieved through molecularly targeted biomarker therapies (tyrosine kinase inhibitors). Prognostic biomarkers are useful in identifying somatic germ line mutations in CRC. This review discusses the current status of research on biomarkers for CRC and summarizes data on emerging therapeutic targets and emerging validated predictive biomarkers for