^
    9d
    Comprehensive Pan-Cancer Analysis of Oncogenic ERBB2 Fusions (AMP 2024)
    Treatment of Ba/F3 or lung cells expressing MDK::ERBB2 with ERBB2 inhibitors (afatinib, poziotinib, tucatinib) blocked phosphorylation of ERBB2 and downstream effectors, and inhibited growth of both cell lines. ERBB2 fusions are rare oncogenic drivers that are candidates for targeted therapy. The subset of recurrent ERBB2 fusions with C-terminal/3' partners may represent an alternative mechanism of fusion oncogenicity.
    Pan tumor
    |
    HER-2 (Human epidermal growth factor receptor 2) • IKZF3 (IKAROS Family Zinc Finger 3) • GRB7 (Growth Factor Receptor Bound Protein 7) • RPS6 (Ribosomal Protein S6) • MDK (Midkine)
    |
    HER-2 amplification • HER-2 mutation • HER-2 expression • HER-2 fusion
    |
    MSK-IMPACT
    |
    Gilotrif (afatinib) • Tukysa (tucatinib) • Pozenveo (poziotinib)
    1m
    Clinical and Genomic Characterization of ERBB2-Altered Gallbladder Cancer: Exploring Differences Between an American and a Chilean Cohort. (PubMed, JCO Glob Oncol)
    The prevalence of lithiasis seems to be higher in Chilean versus US patients with GBC. A similar prevalence of ERBB2 alterations of overall 14% and better OS suggests that a proportion of them could benefit from human epidermal growth factor receptor type 2-targeted therapies. The smaller cohort of Chile, where the disease prevalence is higher, is a reminder and invitation for the need of more robust next-generation sequencing analyses globally.
    Journal • Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 amplification • HER-2 mutation • HER-2 fusion
    |
    MSK-IMPACT
    12ms
    Clinical characteristics and treatment outcomes of HER2 mutation and HER2 fusion in 22 patients with advanced breast cancer. (PubMed, Thorac Cancer)
    Our data demonstrated the clinical benefit of anti-HER2 treatment in Chinese breast cancer patients harboring HER2 mutation and/or HER2 fusion. The value of immunotherapy and treatment selection among individual HER2 variants needs further study.
    Retrospective data • Journal • IO biomarker • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • HER-2 L755P • HER-2 V842I • HER-2 H878Y • HER-2 T862A • HER-2 fusion
    |
    Herceptin (trastuzumab)
    1year
    Pulmonary invasive mucinous adenocarcinoma. (PubMed, Histopathology)
    Accordingly, these unique features require different therapeutic approaches when compared to nonmucinous adenocarcinomas in general. In this article, we review recent updates on the histopathological, clinical, and molecular features of IMAs, and also highlight some unresolved issues for future studies.
    Review • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • NRG1 (Neuregulin 1)
    |
    KRAS mutation • NRG1 fusion • HER-2 fusion
    over1year
    Clinical Implication of HER2 Aberration in Patients With Metastatic Cancer Using Next-Generation Sequencing: A Pan-Tumor Analysis. (PubMed, JCO Precis Oncol)
    In conclusion, we showed that when patients with metastatic cancer receive NGS test, approximately 8.9% have HER2 aberrations in their tumor specimen. Most patients have HER2 amplification, and a small percentage of patients have HER2 fusion. A great majority of patients with HER2 amplification and/or HER2 fusion had HER2 (+) tumor by IHC.
    Journal • Next-generation sequencing • Pan tumor • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2)
    |
    HER-2 overexpression • HER-2 amplification • HER-2 fusion
    over1year
    Characterization of ERBB2 variation and their association with immune response in solid tumours (ESMO 2023)
    Conclusions Our study identified ERBB2 variation patterns among a cohort of Chinese solid tumor patients and demonstrated that ERBB2 abnormality high expression is associated with an activated immune system and a stronger inflammatory response. Our findings offer insights into the potential benefits of using immune checkpoint inhibitors for this type of patient.
    IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • CDK12 (Cyclin dependent kinase 12)
    |
    TP53 mutation • HER-2 overexpression • HER-2 amplification • HER-2 mutation • HER-2 expression • CDK12 mutation • HER-2 fusion
    over1year
    ERBB family fusions are recurrent and actionable oncogenic targets across cancer types. (PubMed, Front Oncol)
    We also establish that adapter-tethered and kinase-tethered fusions are oncogenic and can be inhibited with EGFR or HER2 inhibitors. We further propose a nomenclature system to categorize these fusions into several functional classes.
    Journal
    |
    ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • GRB7 (Growth Factor Receptor Bound Protein 7) • NTRK (Neurotrophic receptor tyrosine kinase)
    |
    HER-2 expression • EGFR expression • ROS1 fusion • HER-2 fusion • NTRK fusion
    |
    MSK-IMPACT
    2years
    Molecular and clinicopathological characteristics of ERBB2 gene fusions in 32,131 Chinese patients with solid tumors. (PubMed, Front Oncol)
    ERBB2 fusion may interfere the effect of anti-HER2-targeted antibody drugs and influence the prognosis of patients with ERBB2 amplification. Prospective clinical trials are warranted to confirm the results in the future.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 amplification • HER-2 mutation • HER-2 fusion • CDK4 mutation
    |
    Herceptin (trastuzumab)
    over2years
    Tissue and Liquid Biopsy–Based Comprehensive Genomic Profiling Reveal Mechanisms of Therapy Resistance and Rare Targetable Alterations in Breast Cancer (MBCC 2022)
    "Conclusions Liquid biopsy profiling provides evidence for therapeutic and selection-driven evolution, with a high frequency of shared driver alterations and a diverse set of in-pathway subclonal acquired alterations. Potentially actionable baseline and acquired alterations identified in liquid biopsies may provide insights into additional treatment options, potentially through combinatorial strategies."
    Liquid biopsy
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • RET (Ret Proto-Oncogene) • FGFR1 (Fibroblast growth factor receptor 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • BRCA (Breast cancer early onset)
    |
    HER-2 positive • KRAS mutation • ER positive • BRAF mutation • NRAS mutation • HER-2 negative • PIK3CA mutation • RET fusion • NF1 mutation • ER mutation • HRAS mutation • ESR1 mutation • FGFR1 fusion • HER-2 fusion
    |
    FoundationOne® Liquid CDx
    over2years
    Clinical and genomic characterization of ERBB2-altered gallbladder cancer. (ASCO 2022)
    ERBB2 amplification and mutation are the most frequent potentially targetable alterations in GBC (14%). ERBB2-driven GBC has higher concurrent alterations of TP53, while KRAS alterations appear to be less frequent. While no particular clinical feature was associated with this subgroup, overall survival was longer.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha)
    |
    HER-2 amplification • PIK3CA mutation • HER-2 fusion
    over2years
    HER2 alterations and prognostic implications in all subtypes of breast cancer. (ASCO 2022)
    ERBB2mts& fusions were observed in all breast cancer subtypes - more commonly in HER2+, metastatic, & lobular histology tumors - & did not influence prognosis. These alterations may reflect response to treatment pressures in HER2+ disease to reactivate HER2-mediated growth pathways following anti-HER2 therapy & may represent a targetable upregulated oncogenic pathway in HER2- disease. Ongoing identification of ERBB2 alterations may augment treatment options for breast cancer pts & clinical outcomes from this approach are under investigation.
    Tumor mutational burden
    |
    HER-2 (Human epidermal growth factor receptor 2) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    TMB-H • HER-2 overexpression • HER-2 negative • HER-2 mutation • HER-2 L755S • HER-2 S310F • ERBB3 mutation • HER-2 D769H • HER-2 fusion
    |
    MI Tumor Seek™
    over3years
    [VIRTUAL] Incidence of ERBB gene fusions (EGFR, ERBB2, ERBB4) across tumor types. (ASCO 2021)
    ERBB gene fusions are detectable at low frequency in various tumor types and may represent a unique genomic subset of cancer . Identification of novel ERBB gene fusions warrants further investigation to determine the potential pathogenicity and actionability of these fusions.
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • SEPTIN14 (Septin 14) • IKZF2 (IKAROS family zinc finger 2)
    |
    TP53 mutation • HER-2 mutation • EGFR fusion • HER-2 fusion
    |
    MSK-IMPACT • MI Tumor Seek™
    over3years
    Study of eFT226 in Subjects With Selected Advanced Solid Tumor Malignancies (clinicaltrials.gov)
    P1/2, N=45, Recruiting, Effector Therapeutics | Trial primary completion date: Apr 2021 --> Oct 2021
    Clinical • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • FGFR2 (Fibroblast growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    KRAS mutation • HER-2 amplification • HER-2 mutation • FGFR2 mutation • FGFR2 fusion • ERBB3 mutation • FGFR1 fusion • HER-2 fusion
    |
    zotatifin (eFT226)
    almost4years
    [VIRTUAL] EGFR, ERBB2 and ERBB4 fusions are recurrent alterations in multiple cancer types (WSMRF 2021)
    Frequency of EGFR, ERBB2 and ERBB4 fusions Conclusions EGFR, HER2 and HER4 fusions are individually rare events but collectively represent up to 1% of all cancers, a significant number of patients with potentially actionable genomic alterations. These data highlight the importance of assaying for these mutations during clinical sequencing and suggest that further investigation into HER fusion biology and potential treatment options would be impactful.
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
    |
    TP53 mutation • HER-2 mutation • HER-2 fusion
    |
    MSK-IMPACT
    over4years
    [VIRTUAL] Genomic landscape and clinicopathological characteristics of lung cancer in young Chinese patients. (ASCO 2020)
    The data suggest that the prevalence of different genetic alterations is both age and sex related. The high level of ALK/ROS1/RET fusions and less CNV in young LC could potentially lead to more effective treatment and better prognosis. We also noted that genomic alterations in young LC were not significantly different across sexes, but the disparity by sex was enormously enlarged in old LC, which might be correlated to their life-long exposures, such as smoking, life styles and sex-affected factors.
    Clinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • FAT1 (FAT atypical cadherin 1)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • HER-2 amplification • PIK3CA mutation • EGFR L858R • EGFR exon 19 deletion • RET fusion • NF1 mutation • ALK fusion • ALK mutation • FGFR1 fusion • MDM2 mutation • EGFR L858R + EGFR exon 19 deletion • HER-2 fusion