Colorectal Cancer Classification and Cell Heterogeneity: A Systems Oncology Approach.

Colorectal cancer is a heterogeneous disease that manifests through diverse clinical scenarios. During many years, our knowledge about the variability of colorectal tumors was limited to the histopathological analysis from which generic classifications associated with different clinical expectations are derived. However, currently we are beginning to understand that under the intense pathological and clinical variability of these tumors there underlies strong genetic and biological heterogeneity. Thus, with the increasing available information of inter-tumor and intra-tumor heterogeneity, the classical pathological approach is being displaced in favor of novel molecular classifications. In the present article, we summarize the most relevant proposals of molecular classifications obtained from the analysis of colorectal tumors using powerful high throughput techniques and devices. We also discuss the role that cancer systems biology may play in the integration and interpretation of the high amount of data generated and the challenges to be addressed in the future development of precision oncology. In addition, we review the current state of implementation of these novel tools in the pathological laboratory and in clinical practice.

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This work was supported by the “Galician Network for Colorectal Cancer Research (REGICC)”, funded by “Xunta de Galicia” (Ref. R2014/039), Spain. Federico Garrido would like to thank the financial support from the following institutions: “Instituto de Salud Carlos III” (CP03/0111, PI12/02031, PI08/1265, PI11/01022, PI11/01386, RETIC RD06/020, RD09/0076/00165, and PT13/0010/0039 projects; all actions co-funded with the European Regional Development Fund, FEDER), Spain; “Junta de Andalucía, Consejería de Salud e Innovación” (PI09/0382 project and CTS143 Research group), Spain; and European Commission (ENACT project: European Network for identification and validation of antigens and biomarkers in cancer and their application in clinical tumour immunology, LSHC-CT-2004-503306).