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    BIOMARKER:

    ERBB3 mutation

    i
    Other names: ERBB3, HER3, LCCS2, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3
    Entrez ID:
    2065
    Related biomarkers:
    Expression
    Mutation
    CNA
    Others
    6d
    ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new. (PubMed, Virchows Arch)
    The authors review the sparse literature on molecular-genetic aberrations involving the epidermal growth factor receptor family of receptor tyrosine kinases (ERBB1/EGFR, ERBB2, ERBB3, and ERBB4) in uterine mesenchymal tumors, a review that suggests that such tumors may be pathologically heterogeneous. The potential clinical significance of demonstrating a targetable ERBB2/ERBB3 tyrosine kinase mutation or other EGFR family aberrations, as well as its distinctive pathologic profile, supports the segregation of the tumor reported herein as a distinct and emerging entity.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ATRX (ATRX Chromatin Remodeler) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • SOX10 (SRY-Box 10) • CD68 (CD68 Molecule) • MME (Membrane Metalloendopeptidase) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLANA (Melan-A) • NTRK (Neurotrophic receptor tyrosine kinase) • PDGFB (Platelet Derived Growth Factor Subunit B) • STAT6 (Signal transducer and activator of transcription 6) • MITF (Melanocyte Inducing Transcription Factor)
    |
    EGFR mutation • HER-2 mutation • CDKN2A deletion • ATRX mutation • ERBB3 mutation • NF1 deletion
    9d
    Prevalence of HER3 Expression in Pancreatic Cancer Patients Treated With Systemic Chemotherapy. (PubMed, Cancer Med)
    A high prevalence of HER3 expression was observed in pancreatic cancer patients after chemotherapy. Our findings indicate that HER3 is a potential therapeutic target for pancreatic cancer, deserving further clinical investigation.
    Retrospective data • Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    TP53 mutation • KRAS mutation • ERBB3 expression • ERBB3 mutation • TP53 mutation + KRAS mutation • KRAS mutation + TP53 mutation
    2ms
    Landscape analysis of breast cancer ovarian metastases reveals biology and potential therapeutic targets (SABCS 2024)
    Our study provides the largest comprehensive characterization of ovarian metastases in patients with breast cancer. It not only deepens our understanding of ILC ovarian metastasis but provides the foundation for future studies aimed at improved prevention and treatment of breast cancer metastasis to the ovary.
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RUNX1 (RUNX Family Transcription Factor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • JAK3 (Janus Kinase 3) • FOXA1 (Forkhead Box A1) • PI3K (Phosphoinositide 3-kinases)
    |
    TP53 mutation • PIK3CA mutation • ERBB3 mutation • CDH1 mutation • JAK3 mutation
    |
    FoundationOne® CDx
    2ms
    Genomic analysis of circulating tumor DNA (ctDNA) from patients with triple-negative, HER2-mutant metastatic breast cancer treated with neratinib as monotherapy or in combination with trastuzumab in the SUMMIT trial (SABCS 2024)
    These findings were consistent with those reported for SUMMIT hormone receptor-positive (HR+) HER2-mutant mBC cohorts, in which patients treated with N or N + fulvestrant (N+F) experienced promising clinical responses but shorter DOR. Although limited by small numbers, addition of T to N in patients with HER2-mutant mTNBC, despite deepening and prolonging response, did not appear to preclude eventual emergence of either on-pathway (ERBB3) or off-pathway (KRAS, TP53) mutations. In contrast to observations in N+F+T-treated patients with HR+, HER2-mutant disease, no additional HER2 alterations were detected upon progression in N+T-treated patients with mTNBC in this small dataset. Future investigations may evaluate clinical utility of sequencing therapies targeted to mutations acquired in response to N-based therapy in patients with HER2-mutant mTNBC.
    Clinical • Combination therapy • Genomic analysis • Circulating tumor DNA • Metastases • Omic analysis
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase)
    |
    TP53 mutation • KRAS mutation • HR positive • HER-2 amplification • HER-2 mutation • KRAS Q61H • ERBB3 mutation • MTOR mutation • HER-2 T798I • TP53 R196*
    |
    MSK-ACCESS
    |
    Herceptin (trastuzumab) • Nerlynx (neratinib) • fulvestrant
    2ms
    Multigene Panel Next-Generation Sequencing Techniques in the Management of Patients with Metastatic Colorectal Carcinoma: The Way Forward for Personalized Treatment? A Single-Center Experience. (PubMed, Int J Mol Sci)
    In total, 40% of patients had druggable molecular alterations, but only 1.1% received genomically guided treatment, suggesting limited application in standard practice. Despite this, expanded gene panel testing can identify actionable mutations, aiding personalized treatment strategies in metastatic CRC, although current eligibility for biomarker-guided trials remains limited.
    Journal • Next-generation sequencing • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • mTOR (Mechanistic target of rapamycin kinase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • JAK1 (Janus Kinase 1)
    |
    KRAS mutation • KRAS G12C • BRAF mutation • PIK3CA mutation • FGFR2 mutation • KRAS G12 • ERBB3 mutation • MTOR mutation
    2ms
    CDX2-Suppressed Colorectal Cancers Possess Potentially Targetable Alterations in Receptor Tyrosine Kinases and Other Colorectal-Cancer-Associated Pathways. (PubMed, Diseases)
    CDX2-suppressed colorectal cancers constitute a genomically distinct subset of colon and rectal cancers that have a lower prevalence of KRAS, APC, and TP53 mutations, but a high prevalence of mutations in less commonly mutated colorectal cancer genes. These alterations could serve as targets for personalized therapeutics in this subset.
    Journal • BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • APC (APC Regulator Of WNT Signaling Pathway) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CDX2 (Caudal Type Homeobox 2)
    |
    TP53 mutation • KRAS mutation • BRAF mutation • ATM mutation • APC mutation • ERBB3 mutation
    2ms
    HER3: Updates and current biology function, targeted therapy and pathologic detecting methods. (PubMed, Life Sci)
    Simultaneously, numerous approaches to HER3 targeted therapy are enumerated, and the clinical detection methods for HER3 that are commonly employed in pathology are sorted and contrasted to offer physicians a range of options. We think that a better knowledge of the mechanisms underlying HER3 in tumors and the advancement of targeted HER3 therapy will contribute to an improved prognosis for cancer patients and an increase in the efficacy of anticancer therapies.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR expression • ERBB3 expression • ERBB3 overexpression • ERBB3 mutation • ERBB3 underexpression
    3ms
    Genetic Profiling of Non-Small Cell Lung Cancer in Moroccan Patients by Targeted Next-Generation Sequencing. (PubMed, Technol Cancer Res Treat)
    Our results regarding the proportion of samples with actionable mutations demonstrate the value of NGS testing for NSCLC patients in a real-world clinical diagnostic setting.
    Journal • Retrospective data • PD(L)-1 Biomarker • IO biomarker • Next-generation sequencing
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • RET (Ret Proto-Oncogene) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • FGFR3 (Fibroblast growth factor receptor 3) • EML4 (EMAP Like 4) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CHEK2 (Checkpoint kinase 2)
    |
    TP53 mutation • KRAS mutation • EGFR mutation • BRAF mutation • PTEN mutation • RET mutation • ROS1 fusion • RET rearrangement • ERBB3 mutation • FGFR3 fusion • EGFR mutation + KRAS mutation
    |
    Oncomine Precision Assay
    5ms
    HER3 Expression Across Genomic Subsets of NSCLC (IASLC-WCLC 2024)
    High ERBB3 expression was associated with better survival. These data support the role of HER3 as a viable therapeutic target across multiple molecular subsets.
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • MET (MET proto-oncogene, receptor tyrosine kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    KRAS mutation • EGFR mutation • KRAS G12C • EGFR L858R • HER-2 expression • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR expression • MET exon 14 mutation • ALK fusion • ERBB3 expression • ROS1 fusion • KRAS G12 • EGFR exon 20 mutation • ERBB3 mutation • KRAS expression
    |
    MI Tumor Seek™
    7ms
    HER3 V104 mutations regulate cell signaling, growth, and drug sensitivity in cancer. (PubMed, Mol Carcinog)
    COS7 cells transiently transfected with the HER3-V104L mutation in the presence of HER binding partners showed higher expression of p-HER3, p-ERK1/2 versus HER3-WT in a NRG-independent manner without any change in AKT signaling. Overall, this study shows the clinical relevance of the HER3 V104L and the V104M mutations and its response to HER2, PI3K and ERK inhibitors.
    Journal
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    HER-2 mutation • HER-2 expression • ERBB3 expression • ERBB3 mutation • ERBB3 V104L • ERBB3 V104M
    7ms
    Based on Immune Microenvironment and Genomic Status, Exploring Immunotherapy in Advanced Hidradenocarcinoma: A Retrospective Analysis. (PubMed, Acta Derm Venereol)
    Evidence-based targets for targeted therapy are lacking. Immunotherapy combined with chemotherapy may be better for most advanced hidradenocarcinoma patients with a noninflammatory microenvironment.
    Retrospective data • Journal • PD(L)-1 Biomarker • IO biomarker • Metastases
    |
    PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CD8 (cluster of differentiation 8)
    |
    PD-L1 expression • TMB-L • ERBB3 mutation
    9ms
    Genetic sequencing and Novel Therapeutic Targets in Perianal Extramammary Paget Disease (EADO 2024)
    We identified MYC amplification and ERBB3 as possible predictors of disease metastases and recurrence. Additional research regarding targetable MYC and ERBB3 therapies are warranted.
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    TP53 mutation • HER-2 mutation • MYC amplification • ERBB3 mutation
    |
    MSK-IMPACT
    9ms
    Genomic and immune microenvironment features influencing chemoimmunotherapy response in gastric cancer with peritoneal metastasis: a retrospective cohort study. (PubMed, Int J Surg)
    This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.
    Retrospective data • Journal • IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CD8 (cluster of differentiation 8) • CDH1 (Cadherin 1) • CD4 (CD4 Molecule) • HLA-DQB1 (Major Histocompatibility Complex, Class II, DQ Beta 1)
    |
    HER-2 mutation • CD8 expression • ERBB3 mutation • CDH1 expression • CDH1 mutation • CTLA4 expression
    9ms
    Urinary comprehensive genomic profiling assists in non-invasive detection and molecular staging of upper tract urothelial carcinoma (AUA 2024)
    uCGP can identify genomic features associated with UTUC and provide definitive results in cases of atypical cytology. Unique genomic patterns provide insight into tumor grade and origin. This study suggests uCGP can provide diagnostic and prognostic information for the evaluation for UTUC.
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • TERT (Telomerase Reverse Transcriptase) • KMT2D (Lysine Methyltransferase 2D) • CREBBP (CREB binding protein) • STAG2 (Stromal Antigen 2) • SOX4 (SRY-Box Transcription Factor 4)
    |
    PIK3CA mutation • HER-2 mutation • ARID1A mutation • KMT2D mutation • CREBBP mutation • ERBB3 mutation • STAG2 mutation • TERT mutation
    |
    UroAmp
    10ms
    Targeting HER2/HER3 co-mutations in metastatic breast cancer: Case reports of exceptional responders to trastuzumab and pertuzumab therapy. (PubMed, Cancer Rep (Hoboken))
    In this report, we present two exceptional responses in hormone receptor-positive, HER2-nonamplified, HER2/HER3 co-mutated metastatic breast cancer patients who were treated with the anti-HER2-directed monoclonal antibodies, trastuzumab and pertuzumab. Both patients acheived exceptional responses to treatment, suggesting that combined trastuzumab, pertuzumab, and endocrine therapy could be a highly effective therapy for these patients and our observations could help prioritize trastuzumab deruxtecan as an early therapeutic choice for patients whose cancers have activating mutations in HER2.
    Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    HER-2 positive • HR positive • HER-2 overexpression • HER-2 mutation • ERBB3 mutation
    |
    Perjeta (pertuzumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    10ms
    Molecular and clinical portrait of HER2-low invasive lobular carcinomas. (PubMed, Mod Pathol)
    In conclusion, HER2-low ILCs exhibit their own particularities, both on clinical-pathological and molecular levels. Our findings call for larger multicenter validation studies.
    Journal
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    HER-2 positive • HER-2 overexpression • HER-2 negative • ERBB3 mutation • ERBB3-L
    10ms
    Translational Insights and Overall Survival in the U31402-A-U102 Study of Patritumab Deruxtecan (HER3-DXd) in EGFR-Mutated NSCLC. (PubMed, Ann Oncol)
    In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • ERBB3 expression • ERBB3 mutation
    |
    patritumab deruxtecan (U3-1402)
    10ms
    Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer. (PubMed, Int J Mol Sci)
    In clinical trials, promising results have come from monoclonal antibodies such as trastuzumab and ramucirumab. Dual inhibitors targeting the PI3K/AKT/mTOR and MAPK signaling pathways were used in vitro studies, also with promising results. The main aim of this review is to present GC incidence and risk factors and the dysregulations of the two protein kinase complexes together with their specific inhibitors.
    Review • Journal
    |
    TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • CDH1 (Cadherin 1)
    |
    TP53 mutation • PIK3CA mutation • ARID1A mutation • ERBB3 mutation
    |
    Herceptin (trastuzumab) • Cyramza (ramucirumab)
    11ms
    Identification of aberrant luminal progenitors and mTORC1 as a potential breast cancer prevention target in BRCA2 mutation carriers. (PubMed, Nat Cell Biol)
    ERBB3 progenitors could generate both ER and ER cells, potentially serving as cells-of-origin for ER-positive or triple-negative cancers. Short-term treatment with an mTORC1 inhibitor substantially curtailed tumorigenesis in a preclinical model of BRCA2-deficient breast cancer, thus uncovering a potential prevention strategy for BRCA2 mutation carriers.
    Journal • BRCA Biomarker
    |
    ER (Estrogen receptor) • BRCA2 (Breast cancer 2, early onset) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    BRCA2 mutation • ER positive • ERBB3 mutation
    11ms
    EGFR-mutation testing, treatment patterns and clinical outcomes in patients with stage IB-IIIA non-small cell lung cancer in Norway-a nationwide cohort study. (PubMed, Cancer Treat Res Commun)
    Although EGFR-mutation testing is increasingly being implemented in the early-stage setting in line with national recommendations, some patients are still not being tested for molecular markers as part of their diagnostic workup-a prerequisite for providing equal access to effective targeted treatments, such as EGFR-TKIs, to eligible patients.
    Clinical data • Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR wild-type • ERBB3 mutation
    12ms
    Molecular Targets and Therapies for Ampullary Cancer. (PubMed, J Natl Compr Canc Netw)
    In this article, we review the approach to tissue acquisition and consideration for molecular testing. Common molecular targets of interest in ampullary cancer are also discussed in this review, including HER2/ERBB2, HER3, tumor mutational burden, microsatellite instability, KRAS, and germline BRCA and ATM mutations, along with emerging and rarer alterations.
    Review • Journal • Tumor mutational burden • BRCA Biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • BRCA (Breast cancer early onset)
    |
    KRAS mutation • HER-2 mutation • ATM mutation • ERBB3 mutation • BRCA mutation
    12ms
    A Study With Tovorafenib (DAY101) as a Treatment Option for Progressive, Relapsed, or Refractory Langerhans Cell Histiocytosis (clinicaltrials.gov)
    P2, N=29, Recruiting, National Cancer Institute (NCI) | Initiation date: Jan 2024 --> Apr 2024
    Trial initiation date
    |
    BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    BRAF V600E • BRAF V600 • ERBB3 mutation
    |
    Ojemda (tovorafenib)
    1year
    A narrative review of antibody-drug conjugates in EGFR-mutated non-small cell lung cancer. (PubMed, Front Oncol)
    Osimertinib, a third-generation tyrosine kinase inhibitor, is approved as first-line therapy for advanced NSCLC and in the adjuvant setting for Stage IB-IIIA resected NSCLC...Trastuzumab deruxtecan has received accelerated FDA approval in HER2-mutated NSCLC. ADCs offer a possible solution to finding a new treatment that could bypass the intracellular resistance mechanism. In this review article, we summarize the mechanism of ADCs and investigational ADCs for EGFR-mutated NSCLC, which include targets to MET amplification, HER3, Trop2, and EGFR, along with other ADC targets being investigated in NSCLC, and discuss future directions that may arise with ADCs in EGFR-mutated NSCLC.
    Review • Journal • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • MET (MET proto-oncogene, receptor tyrosine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • HER-2 amplification • MET amplification • MET mutation • ERBB3 mutation • ERBB3 amplification
    |
    Tagrisso (osimertinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
    1year
    HERTHENA-Lung02: phase III study of patritumab deruxtecan in advanced EGFR-mutated NSCLC after a third-generation EGFR TKI. (PubMed, Future Oncol)
    HERTHENA-Lung02 is the first phase III trial to evaluate the safety and efficacy of HER3-DXd versus PBC in patients with progression on a third-generation EGFR TKI. Clinical Trial Registration: NCT05338970 (clinicaltrials.gov); 2021-005879-40 (EudraCT Number).
    P3 data • Review • Journal • Metastases
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • EGFR expression • ERBB3 expression • ERBB3 mutation
    |
    patritumab deruxtecan (U3-1402)
    1year
    Performance of the OncoUrine test on predicting patients who can avoid Re-TURBT and prognosis: A prospective, multicenter clinical study. (ASCO-GU 2024)
    OncoUrine test after initial TURBT for NMIBC showed promise as to guide patient selection for Re-TURBT and risk stratification in the management of NMIBC. Clinical trial information: NCT05112523.
    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) • FGFR3 (Fibroblast growth factor receptor 3) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TERT (Telomerase Reverse Transcriptase) • ERCC2 (Excision repair cross-complementation group 2) • KDM6A (Lysine Demethylase 6A) • U2AF1 (U2 Small Nuclear RNA Auxiliary Factor 1) • ONECUT2 (One Cut Homeobox 2)
    |
    TP53 mutation • KRAS mutation • PIK3CA mutation • HER-2 mutation • HRAS mutation • U2AF1 mutation • ERBB3 mutation • TERT mutation
    1year
    A Rare Case of CD1a +/CD207 + and S100 - Langerhans Cell Histiocytosis with Multi-System Risk Organ Involvement in Adult (ASH 2023)
    Arginine Vasopressin Deficiency (AVP-D) was diagnosed, and desmopressin was initiated...While it is effective in adults, its limited tolerance favors the use of cytarabine or cladribine. NCT02670707 is an ongoing trial comparing cytarabine monotherapy versus Vinblastine/Prednisone for frontline treatment. BRAF inhibitors are also being increasingly investigated. Prospective trials to optimize the duration of therapy (LCH-IV) and potential combination therapies are currently underway.
    Clinical
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CD20 (Membrane Spanning 4-Domains A1) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CREBBP (CREB binding protein) • JAK1 (Janus Kinase 1) • NOTCH3 (Notch Receptor 3) • ARAF (A-Raf Proto-Oncogene) • CD68 (CD68 Molecule) • CTNNA1 (Catenin Alpha 1) • DICER1 (Dicer 1 Ribonuclease III)
    |
    BRAF V600E • KRAS mutation • BRAF V600 • CD20 positive • ERBB3 mutation • NOTCH3 mutation
    |
    cytarabine • prednisone • cladribine • vinblastine
    1year
    Prognostic and predictive biomarkers for anti-EGFR monoclonal antibody therapy in RAS wild-type metastatic colorectal cancer: a systematic review and meta-analysis. (PubMed, BMC Cancer)
    In RAS wt mCRC patients receiving EGFR-targeted therapy, BRAF mutation is a powerful prognostic and therapy-predictive biomarker, with no effect found for PIK3CA mutation, PTEN mutation or deletion, but the combined biomarker KRAS/NRAS/BRAF/PIK3CA mutations predict resistance to anti-EGFR therapy. Low miR-31-3p expression may have positive prognostic and therapy predictive effects. Evidence on the prognostic and predictive roles of EGFR and its ligands, and HER2/3/4 is insufficient.
    Retrospective data • Review • Journal • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • EREG (Epiregulin) • MIR31 (MicroRNA 31)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • PIK3CA mutation • HER-2 expression • PTEN mutation • ERBB3 expression • RAS mutation • RAS wild-type • ERBB3 mutation • PIK3CA mutation + PTEN mutation • AREG expression • ERBB4 expression • KRAS deletion
    1year
    Study of an Anti-HER3 Antibody, HMBD-001, With or Without Chemotherapy in Patients With Solid Tumors Harboring an NRG1 Fusion or HER3 Mutation (clinicaltrials.gov)
    P1, N=68, Recruiting, Hummingbird Bioscience | Phase classification: P1b --> P1
    Phase classification • Metastases
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1) • EGF (Epidermal growth factor)
    |
    NRG1 fusion • ERBB3 mutation
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
    1year
    Clinical and genomic landscape of ERBB2 and ERBB3 mutated breast cancer (SABCS 2023)
    Here we describe the clinical and genomic characteristics of a large cohort of ERBB2/3-mut breast cancers. We identify a notable enrichment of ERBB2/3-mut in lobular histology and metastatic tumors and tendency for co-alteration with CDH1 and multiple transcription factors reflecting the unique biology of ERBB2/3-mut breast cancers. Further analyses on an expanded cohort (n >6000 pts), including outcomes on HER2-directed antibody-drug conjugates (T-DXd) and targeted therapies such as PI3K inhibitors, will be presented at the 2023 SABCS Annual Meeting.
    Clinical
    |
    HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • RUNX1 (RUNX Family Transcription Factor 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDH1 (Cadherin 1) • FOXA1 (Forkhead Box A1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • GATA3 (GATA binding protein 3)
    |
    HER-2 negative • HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • ERBB3 mutation • HER-2 G778_P780dup • ERBB3 G284R
    |
    MSK-IMPACT
    |
    Enhertu (fam-trastuzumab deruxtecan-nxki)
    1year
    Genomic and immune profiling of breast cancer brain metastases (SABCS 2023)
    This analysis showed moderate discrepancy in subtype call of BrM by tissue preparation (frozen vs. FFPE), with LumB classification showing the highest discrepancy, and more commonly called in FFPE tissues. Subtype concordance between ECT and BrM was relatively high.
    BRCA Biomarker
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • ATM (ATM serine/threonine kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • NF1 (Neurofibromin 1) • IFNG (Interferon, gamma) • CDK4 (Cyclin-dependent kinase 4) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • CD4 (CD4 Molecule) • CCND2 (Cyclin D2) • TGFB1 (Transforming Growth Factor Beta 1)
    |
    BRAF mutation • ATM mutation • PTEN mutation • ERBB3 mutation • CCND2 mutation
    |
    Prosigna™ Breast Cancer Prognostic Gene Signature Assay
    1year
    A self-replicating RNA Precision Immunotherapeutic for Overcoming Resistance to Endocrine Therapy in Estrogen Receptor Positive Breast Cancer (ER+BC) (SABCS 2023)
    The immune cell-mediated elimination of clones expressing the acquired resistance mutations is predicted to prolong endocrine control of ER+BC, in an analogous manner to small molecule or monoclonal antibody targeted therapies, but with a more favorable dosing and adverse event profile due to precise immunologic targeting and no DDI. RBI-1000 is anticipated to enter clinical studies in the first half of 2024.
    IO biomarker
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • PI3K (Phosphoinositide 3-kinases)
    |
    ER positive • HER-2 amplification • HER-2 negative • ER mutation • ESR1 mutation • ERBB3 mutation
    |
    RBI-1000
    1year
    Clinical and Genomic Features of ER-Positive/HER2-negative Metastatic Breast Cancer in AURORA Molecular Screening Initiative (BIG 14-01): Mechanisms of Endocrine Therapy Resistance and Implications for Adjuvant Approaches (SABCS 2023)
    Adjuvant treatment was aromatase inhibitor (AI) +/- ovarian function suppression (OFS) in 288 (46%) pts, while 159 (25%) had tamoxifen only (+/- OFS)... AURORA study sheds light on metastatic tumor alterations acquired under anti-cancer therapy, in ER+/HER2- MBC. We observed a high prevalence of acquired ESR1mut prior to the initiation of first-line therapy, particularly in tumors exposed to adjuvant AI or with primary or secondary ET_resistance. The association of ESR1muts with poorer OS underscores the importance of implementing effective adjuvant ET strategies to prevent the emergence of these mutations.
    Clinical • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4)
    |
    HER-2 positive • TP53 mutation • ER positive • HER-2 negative • PIK3CA mutation • ESR1 mutation • ERBB3 mutation • ER positive + HER-2 negative
    |
    tamoxifen
    1year
    Resistance of Lung Cancer to EGFR-Specific Kinase Inhibitors: Activation of Bypass Pathways and Endogenous Mutators. (PubMed, Cancers (Basel))
    Thus, the net outcome of the SOS response is a greater probability to evolve new mutations. Deeper understanding of the persister-to-resister transformation, along with the development of next-generation TKIs, EGFR-specific proteolysis targeting chimeras (PROTACs), as well as bispecific antibodies, will permit delaying the onset of relapses and prolonging survival of patients with EGFR lung cancer.
    Review • Journal
    |
    EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • AXL (AXL Receptor Tyrosine Kinase)
    |
    ERBB3 mutation
    1year
    Mutational landscape and characteristics of ERBB2 in urothelial carcinoma (ESMO Asia 2023)
    Conclusions The study provided the landscape of ERBB2 alterations in UC that may benefit from anti-HER2 agents. Consideration should be given to developing trials inclusive of patients with UC harboring ERBB2 alterations.
    Tumor mutational burden
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FGFR3 (Fibroblast growth factor receptor 3) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • CDK12 (Cyclin dependent kinase 12) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ERCC2 (Excision repair cross-complementation group 2) • KMT2C (Lysine Methyltransferase 2C)
    |
    TP53 mutation • TMB-H • HER-2 amplification • HER-2 mutation • HER-2 L755S • NF1 mutation • FGFR3 mutation • HER-2 S310F • ERBB3 mutation
    1year
    A phase Ib study of HMBD-001, a monoclonal antibody targeting HER3, with or without chemotherapy in patients with genetic aberrations in HER3 signaling (ESMO Asia 2023)
    The study evaluates HMBD-001 in combination with standard of care chemotherapy in two cohorts: NRG1 fusions in PDAC (HMBD-001 + nab-paclitaxel + gemcitabine) and in NSCLC (HMBD-001 + docetaxel) and HMBD-001 monotherapy in two other cohorts: NRG1 fusions in other solid tumors and selected HER3 ECD mutations across solid tumors. The primary objectives are to determine the safety and tolerability of all combination regimens and to assess the preliminary anti-tumor activity in terms of objective response rate (ORR) by RECIST v1.1 for all regimens. Secondary endpoints include duration of response (DOR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and pharmacokinetic (PK) and immunogenicity profile analysis.
    Clinical • P1 data
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
    |
    NRG1 fusion • ERBB3 mutation • NRG1 fusion
    |
    gemcitabine • docetaxel • albumin-bound paclitaxel • HMBD-001
    1year
    Analysis of real-world implementation of systemic treatment in biliary tract cancer – a single center analysis (DGHO 2023)
    As expected, gemcitabine and cisplatin was the most commonly applied treatment in this setting (54.2%). In the second-line, either FOLFIRI or FOLFOX were usually applied (20.3% and 13.7%, respectively)... Our analysis shows that patients with BTC who were able to undergo multiple treatment lines had an improved overall survival. Further, in the real-world setting, more alternative treatment regimens complement the recommended therapy lines due to participation in clinical trials or patient fitness and comorbidities.
    Clinical • Real-world evidence • Real-world
    |
    BRAF (B-raf proto-oncogene) • FGFR2 (Fibroblast growth factor receptor 2) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A)
    |
    BRAF V600E • BRAF V600 • IDH1 mutation • FGFR2 mutation • FGFR2 fusion • ERBB3 mutation
    |
    cisplatin • gemcitabine • 5-fluorouracil • irinotecan • leucovorin calcium
    1year
    Pin1 inhibitor API-1 sensitizes BRAF-mutant thyroid cancers to BRAF inhibitors by attenuating HER3-mediated feedback activation of MAPK/ERK and PI3K/AKT pathways. (PubMed, Int J Biol Macromol)
    These results, taken together, demonstrate that Pin1 inhibitor API-1 significantly improves the sensitivity of BRAF-mutant thyroid cancer cells to PLX4032. Thus, this study not only determines the potential antitumor activity of Pin1 inhibitor API-1 in thyroid cancer but also offers an alternative therapeutic strategy for BRAF-mutant thyroid cancers by a combination of Pin1 inhibitor and BRAF kinase inhibitor.
    Journal
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • MIR20A (MicroRNA 20a)
    |
    BRAF mutation • ERBB3 mutation
    |
    Zelboraf (vemurafenib)
    over1year
    HERTHENA-Lung01, a Phase II Trial of Patritumab Deruxtecan (HER3-DXd) in Epidermal Growth Factor Receptor-Mutated Non-Small-Cell Lung Cancer After Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy and Platinum-Based Chemotherapy. (PubMed, J Clin Oncol)
    After tumor progression with EGFR TKI therapy and PBC in patients with EGFR-mutated NSCLC, HER3-DXd once every 3 weeks demonstrated clinically meaningful efficacy with durable responses, including in CNS metastases. A phase III trial in EGFR-mutated NSCLC after progression on an EGFR TKI is ongoing (HERTHENA-Lung02; ClinicalTrials.gov identifier: NCT05338970).
    P2 data • Journal
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    EGFR mutation • ERBB3 expression • ERBB3 mutation
    |
    Tagrisso (osimertinib) • patritumab deruxtecan (U3-1402)
    over1year
    Refractory microsatellite stable metastatic colorectal cancer with ERBB2/ERBB3 mutation may be preferred population for regorafenib plus PD-1 inhibitor therapy: a real-world study. (PubMed, Front Oncol)
    A recent REGONIVO trial showed that regorafenib plus nivolumab had an encouraging efficacy in MSS metastatic CRC (mCRC). Regorafenib in combination with PD-1 inhibitor provides a feasible treatment regimen for refractory MSS mCRC with tolerated toxicity. Patients with ERBB2/ERBB3 mutation may be the preferred population for this combination regimen.
    Journal • Real-world evidence • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases
    |
    HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TYK2 (Tyrosine Kinase 2)
    |
    HER-2 mutation • ERBB3 mutation
    |
    Opdivo (nivolumab) • Stivarga (regorafenib)
    over1year
    Mutational spectrum for guiding the decision of adjuvant treatment in patients with resected biliary tract carcinoma. (PubMed, Cancer Med)
    Genomic testing might be useful in guiding the decisions regarding adjuvant treatment in BTC.
    Retrospective data • Journal
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR2 (Fibroblast growth factor receptor 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ARID1A (AT-rich interaction domain 1A) • NF1 (Neurofibromin 1) • PBRM1 (Polybromo 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • TGFBR1 (Transforming Growth Factor Beta Receptor 1) • ACVR1B (Activin A Receptor Type 1B)
    |
    PIK3CA mutation • ARID1A mutation • FGFR2 mutation • NF1 mutation • CDKN2A mutation • PBRM1 mutation • NF2 mutation • ERBB3 mutation
    over1year
    Androgen receptor transcriptional activity is required for heregulin-1β-mediated nuclear localization of the HER3/ErbB3 receptor tyrosine kinase. (PubMed, J Biol Chem)
    Mutations of ErbB3's kinase domain did not affect its localization but was responsible for cell viability in CRPC cells. Taken together, we conclude that AR expression regulated ErbB3 expression, its transcriptional activity suppressed ErbB3 nuclear translocation, and HRG binding to ErbB3 promoted it.
    Journal
    |
    EGFR (Epidermal growth factor receptor) • AR (Androgen receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
    |
    ERBB3 expression • ERBB3 mutation • AR expression
    over1year
    Clinical importance of the range of detectable variants between the Oncomine Dx target test and a conventional single-gene test for EGFR mutation. (PubMed, Sci Rep)
    However, among the other three discordant cases harboring the mutations reportable by the ODxTT, only one patient had a clinical response with short duration. Among the discordant cases for common EGFR mutations between the ODxTT and the conventional single gene test, there are a certain number of suitable patients responsive to EGFR-TKIs, especially when the cause of the discordant results comes from the difference in the range of detectable variants that are reportable between the tests.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • ERBB3 mutation
    |
    Oncomine™ Dx Target Test