Role of Circulating Tumor Cells in Metastatic Colorectal Cancer: Clinical Challenges and Opportunities

Circulating tumour cells (CTCs) have been presumed critical to the metastatic process since 1800. These epithelial cells are disseminated from the primary or metastatic tumor site and can be identified in the peripheral blood of patients. Nowadays, technical advances have rendered it easier to reproducibly and repeatedly sample this population of cells with an acceptable degree of accuracy. Therefore, these cells could become an attractive surrogate for phenotypic and genotypic markers in correlation with the development of molecular targeted therapies. In metastatic colorectal cancer several prospective studies have demonstrated the independent prognostic significance of CTCs and identified the number of CTCs before and during treatment as a predictor for overall survival and disease free survival. However, the underlying molecular characteristics of CTCs associated with outcome remain largely unknown. In this review, the role of CTCs in metastatic colorectal cancer is discussed. The variety of assays that can be used for enrichment and detection steps in CTC detection will be described and the clinical utility of these cells for assessing prognosis and monitoring response to therapy will be analyzed. We will also address the shortcomings of current detection methods that fail to identify a mesenchymal subgroup of CTCs, and briefly address how characterization of these cells can help elucidate the biology of cancer metastases.