ArticleCancer discovery2015
HER2 activating mutations are targets for colorectal cancer treatment.
Article in Cancer discovery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 4 of them syntheses that pooled it.
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
189 citing papers in PubMed, 4 syntheses or guidelines pooled it, 289 citations in OpenAlex.
- Anti-Human Epidermal Growth Factor Receptor 2 therapies in metastatic colorectal cancer: a systematic review and meta-analysis.The oncologist · 2026Pooled it
- Systematic literature review and meta-analysis of HER2 amplification, overexpression, and positivity in colorectal cancer.JNCI cancer spectrum · 2024Pooled it
- A Meta-Analysis to Assess the Efficacy of HER2-Targeted Treatment Regimens in HER2-Positive Metastatic Colorectal Cancer (mCRC).Current oncology (Toronto, Ont.) · 2023Pooled it
- Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review.International journal of molecular sciences · 2021Pooled it
- Efficacy and Genomic Analysis of HER2-Mutant Metastatic Triple-Negative Breast Cancer Treated with Neratinib Alone or with Trastuzumab in the SUMMIT Basket Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Trial
- NSABP FC-11: A phase II study of neratinib plus trastuzumab or neratinib plus cetuximab in patients with "quadruple wild-type" (KRAS/NRAS/BRAF/PIK3CA) metastatic colorectal cancer based on HER2 status: amplified, non-amplified (wild-type), or mutated.Cancer chemotherapy and pharmacology · 2025Trial
- Pyrotinib Plus Trastuzumab as an Effective Later-Line Therapeutic Strategy for HER2-Positive Metastatic Colorectal Cancer: Results from a Phase II Study.Drug design, development and therapy · 2025Trial
- Targeting HER2-mutant metastatic cervical cancer with neratinib: Final results from the phase 2 SUMMIT basket trial.Gynecologic oncology · 2024Trial
- Neratinib + fulvestrant + trastuzumab for HR-positive, HER2-negative, HER2-mutant metastatic breast cancer: outcomes and biomarker analysis from the SUMMIT trial.Annals of oncology : official journal of the European Society for Medical Oncology · 2023Trial
- Trial
- Trial
- Prognostic Value of BRAF and KRAS Mutations in MSI and MSS Stage III Colon Cancer.Journal of the National Cancer Institute · 2017Trial
- Recent advances in HER2-targeted inhibitors for cancer therapy.Pharmaceutical science advances · 2026Review
- HER2-Targeted Therapy for Metastatic Colorectal Cancer: Current Evidence, Patient Selection, and Practical Treatment Sequencing.Journal of gastrointestinal cancer · 2026Review
- Exosomes in Colorectal Cancer: From Tumor Biology to Diagnostic and Therapeutic Applications.Medicina (Kaunas, Lithuania) · 2026Review
- Genomic landscape and clinical characteristics of ERBB2/HER2-mutated colorectal cancers.The oncologist · 2026Article
- Preclinical in vitro and in vivo activity of trastuzumab deruxtecan againstGynecologic oncology reports · 2026Article
- Prognostic and Treatment-Specific Predictive Implications of HER2 Expression in RAS Wild-Type Metastatic Colorectal Cancer: A Multicenter Retrospective Real-World Study.Journal of clinical medicine · 2026Article
- Review
- Molecular Targeting of EGFR, BRAF, and HER2 Signaling in Colorectal Cancer: Contemporary Advances with Panitumumab, Encorafenib, and Tucatinib.Journal of clinical medicine · 2026Review
129 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledThe Cancer Genome Atlas project identified HER2 somatic mutations and gene amplification in 7% of patients with colorectal cancer. Introduction of the HER2 mutations S310F, L755S, V777L, V842I, and L866M into colon epithelial cells increased signaling pathways and anchorage-independent cell growth, indicating that they are activating mutations. Introduction of these HER2 activating mutations into colorectal cancer cell lines produced resistance to cetuximab and panitumumab by sustaining MAPK phosphorylation. HER2 mutants are potently inhibited by low nanomolar doses of the irreversible tyrosine kinase inhibitors neratinib and afatinib. HER2 gene sequencing of 48 cetuximab-resistant, quadruple (KRAS, NRAS, BRAF, and PIK3CA) wild-type (WT) colorectal cancer patient-derived xenografts (PDX) identified 4 PDXs with HER2 mutations. HER2-targeted therapies were tested on two PDXs. Treatment with a single HER2-targeted drug (trastuzumab, neratinib, or lapatinib) delayed tumor growth, but dual HER2-targeted therapy with trastuzumab plus tyrosine kinase inhibitors produced regression of these HER2-mutated PDXs. SIGNIFICANCE: HER2 activating mutations cause EGFR antibody resistance in colorectal cell lines, and PDXs with HER2 mutations show durable tumor regression when treated with dual HER2-targeted therapy. These data provide a strong preclinical rationale for clinical trials targeting HER2 activating mutations in metastatic colorectal cancer.
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.