From tumour heterogeneity to advances in precision treatment of colorectal cancer
Top Cited Papers
- 6 December 2016
- journal article
- review article
- Published by Springer Science and Business Media LLC in Nature Reviews Clinical Oncology
- Vol. 14 (4), 235-246
- https://doi.org/10.1038/nrclinonc.2016.171
Abstract
In recent years, the high heterogeneity of colorectal cancer (CRC) has become evident. Hence, biomarkers need to be developed that enable the stratification of patients with CRC into different prognostic subgroups and in relation to response to therapies, according to the distinctive tumour biology. Currently, only RAS-mutation status is used routinely as a negative predictive marker to avoid treatment with anti-EGFR agents in patients with metastatic CRC, and mismatch-repair status can guide the use of adjuvant chemotherapy in patients with early stage colon cancer. Advances in molecular biology over the past decade have enabled a better understanding of the development of CRC, as well as the more-precise use of innovative targeted therapies for this disease, and include three fundamental achievements. First, the availability of large databases to capture and store the genomic landscape of patients with CRC, providing information on the genes that are frequently deregulated in CRC. Second, the possibility of using gene-expression profiling to differentiate the subtypes of CRC into prognostic groups. Third, results from highly sensitive next-generation sequencing analyses have led to an appreciation of the extensive intratumoural heterogeneity of CRC. Herein, we discuss these advances and place them into the clinical context, and present the novel targets and therapeutic opportunities that are on the horizon.This publication has 173 references indexed in Scilit:
- Cancer-initiating cells derived from human rectal adenocarcinoma tissues carry mesenchymal phenotypes and resist drug therapiesCell Death & Disease, 2013
- Gene expression patterns unveil a new level of molecular heterogeneity in colorectal cancerThe Journal of Pathology, 2013
- Gene Expression Classification of Colon Cancer into Molecular Subtypes: Characterization, Validation, and Prognostic ValuePLoS Medicine, 2013
- ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapyBritish Journal of Cancer, 2013
- A robust genomic signature for the detection of colorectal cancer patients with microsatellite instability phenotype and high mutation frequencyThe Journal of Pathology, 2012
- Recurrent R-spondin fusions in colon cancerNature, 2012
- Comprehensive molecular characterization of human colon and rectal cancerNature, 2012
- The molecular evolution of acquired resistance to targeted EGFR blockade in colorectal cancersNature, 2012
- Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancerNature, 2012
- Effect of Oxaliplatin, Fluorouracil, and Leucovorin With or Without Cetuximab on Survival Among Patients With Resected Stage III Colon CancerJAMA, 2012