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From tumour heterogeneity to advances in precision treatment of colorectal cancer
Open accessAbstract
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.
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“5-FU/LV is useful in palliative therapy for mCRC, but the development of effective doublet combination therapy regimens, including FOLFOX (folinic acid (leucovorin), 5-FU, oxaliplatin) and FOLFIRI (leucovorin, 5-FU, irinotecan) [10], resulted in significant survival advantages.”
From Recent Advances in Therapeutic Strategies to Improve Colorectal Cancer Treatment (2024) · cites this paper as [10]
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Metadata
- Authors
- Punt, C. J. A., Koopman, M., & Vermeulen, L.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- University Medical Center Utrecht (NL)
- Corresponding author
- Punt, Cornelis J. A.
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2016-12-06
- Volume
- 14
- Issue
- 4
- Pages
- 235-246
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- OpenAlex
- W2560375214
- Cited by
- 654
- References
- 177
- Citations by year
- 2026: 38 · 2025: 41 · 2024: 87 · 2023: 79 · 2022: 88 · 2021: 96 · 2020: 83 · 2019: 57 · 2018: 56 · 2017: 28
- FWCI
- 4.73
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Utrecht University Repository (Utrecht University) (submittedVersion)
- Funders
- Nederlandse Organisatie voor Wetenschappelijk Onderzoek
- Maag Lever Darm Stichting (MLDS-CDG 14-03)
- H2020 European Research Council (638193)
- Topics
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Health Sciences › Medicine › Oncology › Colorectal Cancer Surgical Treatments
- Keywords
- colorectal cancer, intratumoral heterogeneity, precision medicine, targeted therapy, gene expression profiling, tumor subtypes, prognostic factors, predictive biomarkers, RAS mutations, DNA mismatch repair, anti-EGFR therapy, adjuvant chemotherapy, next-generation sequencing
- MeSH terms
- Antineoplastic Combined Chemotherapy Protocols, Forecasting, Humans, Immunotherapy, Neoplasm Metastasis, Neoplasm Proteins, Neoplasm Staging, Prognosis, Quality of Health Care, Colorectal Neoplasms, Treatment Outcome, Genetic Heterogeneity, Therapies, Investigational, Proto-Oncogene Proteins B-raf, DNA Mismatch Repair, Early Detection of Cancer, Precision Medicine, Molecular Targeted Therapy
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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