title: From tumour heterogeneity to advances in precision treatment of colorectal cancer.
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.
authors.affiliation: Department of Medical Oncology, Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, Netherlands.
authors.forename: Cornelis J A
authors.initials: CJ
authors.lastname: Punt
authors.affiliation: Department of Medical Oncology, University Medical Centre Utrecht, Heidelberglaan 100, 3584CX Utrecht, Netherlands.
authors.forename: Miriam
authors.initials: M
authors.lastname: Koopman
authors.affiliation: Laboratory for Experimental Oncology and Radiobiology (LEXOR), Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, Netherlands.|Centre for Experimental Molecular Medicine (CEMM), Academic Medical Centre, University of Amsterdam, Meibergdreef 9, 1105AZ Amsterdam, Netherlands.
authors.forename: Louis
authors.initials: L
authors.lastname: Vermeulen
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000235:genetics / Q000628:therapy*; D053843:DNA Mismatch Repair / Q000235:genetics; D055088:Early Detection of Cancer; D005544:Forecasting; D018740:Genetic Heterogeneity; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D058990:Molecular Targeted Therapy / Q000639:trends; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000235:genetics; D009367:Neoplasm Staging; D057285:Precision Medicine / Q000639:trends*; D011379:Prognosis; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors / Q000235:genetics; D011787:Quality of Health Care; D035703:Therapies, Investigational / Q000379:methods; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf