ArticlePloS one2016
BRAF, PIK3CA, and HER2 Oncogenic Alterations According to KRAS Mutation Status in Advanced Colorectal Cancers with Distant Metastasis.
Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 2 of them syntheses that pooled it.
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Who cites it
34 citing papers in PubMed, 2 syntheses or guidelines pooled it, 58 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
- Signal transduction pathway mutations in gastrointestinal (GI) cancers: a systematic review and meta-analysis.Scientific reports · 2020Pooled it
- HER2-related biomarkers predict clinical outcomes with trastuzumab deruxtecan treatment in patients with HER2-expressing metastatic colorectal cancer: biomarker analyses of DESTINY-CRC01.Nature communications · 2024Trial
- Characterization of Korean Colorectal Cancer Reveals Novel Driver Gene and Clinically Relevant Mutations.MedComm · 2026Article
- Radical treatment for metastasis of HER2-positive rectal adenocarcinoma to the liver: A case report and literature review.Oncology letters · 2025Article
- Advancements in Targeted Therapies for Colorectal Cancer: Overcoming Challenges and Exploring Future Directions.Cancers · 2025Review
- Plasma ctDNA enhances the tissue-based detection of oncodriver mutations in colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Article
- HER2-Positive Metastatic Colorectal Cancer.Current treatment options in oncology · 2024Review
- Treatment options for HER2-expressing colorectal cancer: updates and recent approvals.Therapeutic advances in medical oncology · 2024Review
- A comprehensive appraisal of HER2 heterogeneity in HER2-amplified and HER2-low colorectal cancer.British journal of cancer · 2023Article
- Final results of DESTINY-CRC01 investigating trastuzumab deruxtecan in patients with HER2-expressing metastatic colorectal cancer.Nature communications · 2023Article
- Clinical Relevance of Targeted Therapy and Immune-Checkpoint Inhibition in Lung Cancer.Pharmaceutics · 2023Review
- New developments in targeted therapy for metastatic colorectal cancer.Therapeutic advances in medical oncology · 2023Review
- EGFR, HER2, and HER3 protein expression in paired primary tumor and lymph node metastasis of colorectal cancer.Scientific reports · 2022Article
- Precision oncology in metastatic colorectal cancer - from biology to medicine.Nature reviews. Clinical oncology · 2021Review
- Clinicopathologic and Prognostic Association of GRP94 Expression in Colorectal Cancer with Synchronous and Metachronous Metastases.International journal of molecular sciences · 2021Article
- LRIG1 expression and colorectal cancer prognosis.BMC medical genomics · 2021Article
- Review
- Evaluation of molecular subtypes and clonal selection during establishment of patient-derived tumor xenografts from gastric adenocarcinoma.Communications biology · 2020Article
- Prevalence, prognosis and predictive status of HER2 amplification in anti-EGFR-resistant metastatic colorectal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2020Review
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAnti-EGFR antibody-based treatment is an important therapeutic strategy for advanced colorectal cancer (CRC); despite this, several mutations--including KRAS, BRAF, and PIK3CA mutations, and HER2 amplification--are associated with the mechanisms underlying the development of resistance to anti-EGFR therapy. The aim of our study was to investigate the frequencies and clinical implications of these genetic alterations in advanced CRC.
methodsKRAS, BRAF, and PIK3CA mutations were determined by Cobas real-time polymerase chain reaction (PCR) in 191 advanced CRC patients with distant metastasis. Microsatellite instability (MSI) status was determined by a fragmentation assay and HER2 amplification was assessed by silver in situ hybridization. In addition, KRAS mutations were investigated by the Sanger sequencing method in 97 of 191 CRC cases.
resultsMutations in KRAS, BRAF, and PIK3CA were found in 104 (54.5%), 6 (3.1%), and 25 (13.1%) cases of advanced CRC, respectively. MSI-high status and HER2 amplification were observed in 3 (1.6%) and 16 (8.4%) cases, respectively. PIK3CA mutations were more frequently found in KRAS mutant type (18.3%) than KRAS wild type (6.9%) (P = 0.020). In contrast, HER2 amplifications and BRAF mutations were associated with KRAS wild type with borderline significance (P = 0.052 and 0.094, respectively). In combined analyses with KRAS, BRAF and HER2 status, BRAF mutations or HER2 amplifications were associated with the worst prognosis in the wild type KRAS group (P = 0.004). When comparing the efficacy of detection methods, the results of real time PCR analysis revealed 56 of 97 (57.7%) CRC cases with KRAS mutations, whereas Sanger sequencing revealed 49 cases (50.5%).
conclusionsKRAS mutations were found in 54.5% of advanced CRC patients. Our results support that subgrouping using PIK3CA and BRAF mutation or HER2 amplification status, in addition to KRAS mutation status, is helpful for managing advanced CRC patients.
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