ArticleGut2013
A combined oncogenic pathway signature of BRAF, KRAS and PI3KCA mutation improves colorectal cancer classification and cetuximab treatment prediction.
Article in Gut, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 130 citations in OpenAlex.
- A randomized, open-label, two-cycle, two-crossover phase I clinical trial comparing the bioequivalence and safety of afatinib and GiotrifJournal of cancer research and clinical oncology · 2023Trial
- Prospective Biomarker Study in Advanced RAS Wild-Type Colorectal Cancer: POSIBA Trial (GEMCAD 10-02).The oncologist · 2019Trial
- Trial
- KRAS signaling networks, mutational heterogeneity, and emerging therapeutic strategies for cancer treatment.Biomarker research · 2026Review
- Inference of upstream-mutation and metabolomic-signature causality identifies prognostic biomarkers and therapeutic targets in pancreatic cancer.Nature communications · 2026Article
- Adipose-tumor crosstalk in colorectal cancer: Identifying (Epi)genetic biomarkers for tumor progression and cachexia.Cell death & disease · 2025Article
- Modulation of the cytoskeleton for cancer therapy.Frontiers in cell and developmental biology · 2025Article
- Dissected subgroups predict the risk of recurrence of stage II colorectal cancer and select rational treatment.Frontiers in immunology · 2023Article
- Insights and Strategies of Melanoma Immunotherapy: Predictive Biomarkers of Response and Resistance and Strategies to Improve Response Rates.International journal of molecular sciences · 2022Review
- Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer.Nature genetics · 2022Article
- Tumor cell intrinsic and extrinsic features predict prognosis in estrogen receptor positive breast cancer.PLoS computational biology · 2022Article
- Pathway-Based Personalized Analysis of Pan-Cancer Transcriptomic Data.Biomedicines · 2021Article
- Pathway signatures derived from on-treatment tumor specimens predict response to anti-PD1 blockade in metastatic melanoma.Nature communications · 2021Article
- Targeting "undruggable" c-Myc protein by synthetic lethality.Frontiers of medicine · 2021Review
- Common and mutation specific phenotypes of KRAS and BRAF mutations in colorectal cancer cells revealed by integrative -omics analysis.Journal of experimental & clinical cancer research : CR · 2021Article
- eVIP2: Expression-based variant impact phenotyping to predict the function of gene variants.PLoS computational biology · 2021Article
- Proteomic Profiling of BRAFV600E Mutant Colon Cancer Cells Reveals the Involvement of Nucleophosmin/c-Myc Axis in Modulating the Response and Resistance to BRAF Inhibition by Vemurafenib.International journal of molecular sciences · 2021Article
- Article
- Multi gene mutation signatures in colorectal cancer patients: predict for the diagnosis, pathological classification, staging and prognosis.BMC cancer · 2021Article
- Systemic therapy in addition to cytoreduction and hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: recent insights from clinical studies and translational research.Journal of gastrointestinal oncology · 2021Review
18 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
10 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo develop gene expression profiles that characterise KRAS-, BRAF- or PIK3CA-activated- tumours, and to explore whether these profiles might be helpful in predicting the response to the epidermal growth factor receptor (EGFR) pathway inhibitors better than mutation status alone.
designFresh frozen tumour samples from 381 colorectal cancer (CRC) patients were collected and mutations in KRAS, BRAF and PIK3CA were assessed. Using microarray data, three individual oncogenic and a combined model were developed and validated in an independent set of 80 CRC patients, and in a dataset from metastatic CRC patients treated with cetuximab.
results175 tumours (45.9%) harboured oncogenic mutations in KRAS (30.2%), BRAF (11.0%) and PIK3CA (11.5%). Activating mutation signatures for KRAS (75 genes), for BRAF (58 genes,) and for PIK3CA (49 genes) were developed. The development of a combined oncogenic pathway signature-classified tumours as 'activated oncogenic', or as 'wildtype-like' with a sensitivity of 90.3% and a specificity of 61.7%. The identified signature revealed other mechanisms that can activate ERK/MAPK pathway in KRAS, BRAF and PIK3CA wildtype patients. The combined signature is associated with response to cetuximab treatment in patients with metastatic CRC (HR 2.51, p<0.0009).
conclusionA combined oncogenic pathway signature allows the identification of patients with an active EGFR-signalling pathway that could benefit from downstream pathway inhibition.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.