ArticleInternational journal of cancer2019
ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer.
Article in International journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 47 citations in OpenAlex.
- Molecular convergence in gallbladder cancer: MEK-ERK signalling at the crossroads of oncogenic hubs and pathway cross-talks.Cancer cell international · 2026Review
- Disparities in Gallbladder Cancer: Epidemiology, Molecular Mechanisms, and Clinical Implications.Molecular biology reports · 2026Review
- Revealing the Potential Associations of Mutation-Related Genes with Lymph Node Metastasis in Gallbladder Cancer Through Transcriptome and Exome Sequencing.Biomedicines · 2026Article
- Article
- Shared molecular mechanisms of common differentially expressed genes (C-DEGs) linking gallbladder stones to carcinogenesis: integrated bioinformatics and experimental validation.Cancer cell international · 2026Article
- Article
- Epidermal Growth Factor Receptor (EGFR) and SMAD4 negatively correlated in the progression of gallbladder cancer in Eastern Indian patients.BMC gastroenterology · 2024Article
- Gallbladder cancer: Progress in the Indian subcontinent.World journal of clinical oncology · 2024Review
- Long-term survival was achieved through multidisciplinary treatment of a patient with gallbladder carcinosarcoma accompanied by KRAS mutation: a case report and literature review.Frontiers in oncology · 2024Article
- Identification of genes associated with gall bladder cell carcinogenesis: Implications in targeted therapy of gall bladder cancer.World journal of gastrointestinal oncology · 2023Review
- Next generation sequencing uncovers multiple miRNAs associated molecular targets in gallbladder cancer patients.Scientific reports · 2023Article
- Article
- Application value of whole exome sequencing in screening and identifying novel mutations of hypopharyngeal cancer.Scientific reports · 2023Article
- Gallbladder cancer.Nature reviews. Disease primers · 2022Review
- Impact of Molecular Tumor Board on the Clinical Management of Patients With Cancer.JCO global oncology · 2022Article
- Article
- Establishment and characterization of an immortalized epithelial cell line from human gallbladder.Frontiers in oncology · 2022Article
- Gallbladder Cancer: Current Insights in Genetic Alterations and Their Possible Therapeutic Implications.Cancers · 2021Review
- Molecular characterization of lung squamous cell carcinoma tumors reveals therapeutically relevant alterations.Oncotarget · 2021Article
- Overview of current targeted therapy in gallbladder cancer.Signal transduction and targeted therapy · 2020Review
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Authors and funding
25 authors at 2 institutions in 1 country.
Funding
Abstract
The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n = 25) and recurrent mutations in 14% tumors (n = 44); along with co-occurring KRAS mutation in 7% tumors (n = 44). We demonstrate that ERBB2 heterodimerizes with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells. Consistent with this, treatment with ERBB2-specific, EGFR-specific shRNA or with a covalent EGFR family inhibitor Afatinib inhibits tumor-associated characteristics of the gallbladder cancer cells. Furthermore, we observe an in vivo reduction in tumor size of gallbladder xenografts in response to Afatinib is paralleled by a reduction in the amounts of phospho-ERK, in tumors harboring KRAS (G13D) mutation but not in KRAS (G12V) mutation, supporting an essential role of the ErbB pathway. In overall, besides implicating ERBB2 as an important therapeutic target under neo-adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.
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