Abstract

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.

Highlights

  • Colorectal cancer is a complex disease with a variable clinical course and with important divergences in the response to treatment, even in tumors with similar histopathological characteristics

  • The current classification of colorectal cancer in a limited number of subtypes should be abandoned and a move made towards the molecular characterization of each tumor as a single entity in order to advance in the implementation of precision oncology [28]

  • In addition to the variability in morphological, phenotypic, functional, or genetic characteristics, the heterogeneity in colorectal cancer can be found in aspects related to the expression of molecules involved in antitumor immune-surveillance, specially the major histocompatibility complex (MHC)

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Summary

A Systems Oncology Approach

Moisés Blanco-Calvo 1, Ángel Concha 1,2, Angélica Figueroa 1, Federico Garrido 3,4,5 and Manuel Valladares-Ayerbes 1,6,*. UGC de Labortorio Clínico, Hospital Universitario Virgen de las Nieves, Servicio de Análisis Clínicos, Avenida de las Fuerzas Armadas, 2, 18009 Granada, Spain. Instituto de Investigacion Biosanitaria de Granada (IBISGranada), Avenida de las Fuerzas Armadas, 2, 18009 Granada, Spain; Medical Oncology Department, Complexo Hospitalario Universitario A Coruña (CHUAC),

Introduction
Sources of Heterogeneity in Colorectal Cancer
Novel Molecular Classifications of Colorectal Cancer
Cell-to-Cell Heterogeneity in Colorectal Cancer
Immunological Heterogeneity in Colorectal Cancer
Heterogeneity in Disseminated and Metastatic Disease
Clinical Implications of Heterogeneity in Metastatic Disease
Future Directions
Findings
Conflicts of Interest
Full Text
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