Biomarker-guided therapy for colorectal cancer: strength in complexity
Open accessAbstract
The number of molecularly stratified treatment options available to patients with colorectal cancer (CRC) is increasing, with a parallel rise in the use of biomarkers to guide prognostication and treatment decision-making. The increase in both the number of biomarkers and their use has resulted in a progressively complex situation, evident both from the extensive interactions between biomarkers and from their sometimes complex associations with patient prognosis and treatment benefit. Current and emerging biomarkers also reflect the genomic complexity of CRC, and include a wide range of aberrations such as point mutations, amplifications, fusions and hypermutator phenotypes, in addition to global gene expression subtypes. In this Review, we provide an overview of current and emerging clinically relevant biomarkers and their role in the management of patients with CRC, illustrating the intricacies of biomarker interactions and the growing treatment opportunities created by the availability of comprehensive molecular profiling.
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Approximately 40% of CRCs harbor oncogenic KRAS mutations, mainly G12D, G12V, and G13D, which can sustainedly activate the MAPK signaling pathway.
“Approximately 40% of CRCs harbor oncogenic KRAS mutations, mainly G12D, G12V, and G13D, which can sustainedly activate the MAPK signaling pathway [2, 3].”
From Genome-wide CRISPR-cas9 knockout screening identifies GRB7 as a driver for MEK inhibitor resistance in KRAS mutant colon cancer (2022) · cites this paper as [3]
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ALK, ROS1, and NTRK Rearrangements in Metastatic Colorectal Cancer
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Self-citationHER2 Activating Mutations Are Targets for Colorectal Cancer Treatment
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Self-citationHypermethylator Phenotype in Sporadic Colon Cancer: Study on a Population-Based Series of 582 Cases
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Trial watch: Immunogenic cell death induction by anticancer chemotherapeutics
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EMT is the dominant program in human colon cancer
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Prognostic Value ofBRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer
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Self-citationComprehensive Intrametastatic Immune Quantification and Major Impact of Immunoscore on Survival
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Targeting the human epidermal growth factor receptor 2 (HER2) oncogene in colorectal cancer
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Self-citationTargeting PTPRK-RSPO3 colon tumours promotes differentiation and loss of stem-cell function
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Immune Escape and Survival Mechanisms in Circulating Tumor Cells of Colorectal Cancer
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Identification of a Poor-PrognosisBRAF-Mutant–Like Population of Patients With Colon Cancer
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BRAF V600E Mutant Colorectal Cancer Subtypes Based on Gene Expression
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“Approximately 40% of CRCs harbor oncogenic KRAS mutations, mainly G12D, G12V, and G13D, which can sustainedly activate the MAPK signaling pathway [2, 3].”
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- Authors
- Sveen, A., Kopetz, S., & Lothe, R. A.
- Affiliations
- Oslo University Hospital (NO)
- The University of Texas MD Anderson Cancer Center (US)
- Corresponding author
- Sveen, Anita
- Venue
- Nature Reviews Clinical Oncology
- Published
- 2019-07-09
- Volume
- 17
- Issue
- 1
- Pages
- 11-32
- ISSN
- 1759-4774 (ISSN-L)
- 1759-4782
- PMC
- PMC7577509
- OpenAlex
- W2957125530
- Cited by
- 320
- References
- 319
- Citations by year
- 2026: 16 · 2025: 39 · 2024: 55 · 2023: 44 · 2022: 57 · 2021: 65 · 2020: 40 · 2019: 4
- FWCI
- 3.96
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Nature Reviews Clinical Oncology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (KL2TR000370)
- National Cancer Institute (R01CA184843, P50CA221707, R01CA218230, R01CA187238, P30CA016672)
- National Center for Advancing Translational Sciences
- 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, biomarkers, biomarker interaction, molecular stratification, targeted therapy, prognostic factors, molecular profiling, gene expression subtypes, hypermutator phenotype, gene amplification, gene fusion, point mutations, treatment decision-making
- MeSH terms
- Clinical Trials as Topic, Humans, Prognosis, Biomarkers, Tumor, Colorectal Neoplasms, Precision Medicine, Molecular Targeted Therapy, Molecular Medicine
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