Heterogeneity in Colorectal Cancer: A Challenge for Personalized Medicine?

Abstract

High inter-patient variability and high spatial heterogeneity are features of colorectal cancer (CRC). This may influence the molecular characterization of tumor tissue, now mandatory for patients with metastatic CRC who are candidates for treatment with an anti-EGFR mAb, as false-negative results can occur, leading to non optimal therapy. Moreover, temporal molecular heterogeneity during treatment is known to influence the response to therapy and prognosis. We present a literature overview of advances made in characterizing molecular heterogeneity in CRC, underlining that the analysis of liquid biopsy could represent an efficient non-invasive tool to overcome the problem. We believe that understanding CRC heterogeneity is fundamental for a more accurate diagnosis, for selecting the best targets to ensure prolonged antitumor response, and for monitoring minimal residual disease and the onset of resistance to therapy, all essential components of successful personalized treatment.

Genetic Alterations of Metastatic Colorectal Cancer

“…Study of intratumor heterogeneity (ITH) is fundamental from both a biological and clinical perspective, to understand the genomic changes driving the evolution of the malignant process up to metastasis generation. Several studies have shown that CRCs display a consistent degree of spatial intratumor heterogeneity; particularly, three types of spatial heterogeneity of CRCs have been described: (i) ITH related to the existence of genetic differences at the level of tumor cells within the primary tumor; (ii) ITH related to differences at the level of various metastatic lesions within a single patient; (iii) ITH related to the existence of genetic differences within the cells of a single metastatic lesion (intrametastatic heterogeneity) [ 46 ].…”

Distant Metastasis in Colorectal Cancer Patients—Do We Have New Predicting Clinicopathological and Molecular Biomarkers? A Comprehensive Review

“…At the time of diagnosis, malignant tumors contain multiple cell populations with diverse biological heterogeneity that is not restricted to primary lesions [ 32 , 33 ]. The clonal origin and genetic heterogeneity of CRCs and heterogeneity between primary tumors and liver metastases have been recently addressed.…”

Mast Cells, microRNAs and Others: The Role of Translational Research on Colorectal Cancer in the Forthcoming Era of Precision Medicine

“…Colorectal cancer (CRC) is a heterogeneous disease [ 1 ], molecularly and anatomically [ 2 ], that develops in a multi-step process [ 3 ] requiring the accumulation of several genetic or epigenetic mutations that lead to the gradual transformation of normal mucosa into cancer.…”