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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:
Related biomarkers:
13d
New trial • Real-world evidence • Real-world
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KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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KRAS mutation • EGFR mutation • KRAS G12C • EGFR exon 20 insertion • ERBB3 expression • KRAS G12 • EGFR exon 20 mutation • ERBB3 mutation
13d
Zebrafish her3 knockout impacts developmental and cancer-related gene signatures. (PubMed, Dev Biol)
Several cancer-related gene pathways are impacted, including the inhibition of matrix metalloproteinases. Altogether, this new model is a powerful system to study her3/HES3-mediated neural development and its misappropriation in cancer contexts.
Journal • Gene Signature
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • SOX10 (SRY-Box 10) • NEUROG1 (Neurogenin 1)
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ERBB3 expression • ERBB3 mutation
13d
A self-replicating RNA precision medicine approach to overcoming resistance to endocrine therapy in ER+BC (AACR 2023)
RBI-1000 is a candidate using a novel type of self-replicating RNA (srRNA) to generate robust immunity directed against acquired resistance mutations that develop in ER+ breast cancer (ER+ BC) in response to endocrine therapy...Priming of T cells against acquired mutations is also confirmed in human HLA-transgenic mice. 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.
IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule) • PI3K (Phosphoinositide 3-kinases)
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EGFR mutation • HER-2 amplification • EGFR T790M • ALK mutation • ERBB3 mutation
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RBI-1000
13d
Zebrafish her3knockout impacts developmental and rhabdomyosarcoma-related gene signatures (AACR 2023)
To complement our zebrafish model, we are developing a double-inducible cell line model consisting of a tetracycline-inducible HES3 and a cumate-inducible PAX3-FOXO1 to further investigate the hypothesized cooperation between her3/HES3 and PAX3-FOXO1 in fusion-positive rhabdomyosarcoma. These two systems will allow us to elucidate conserved mechanisms of cooperation between HES3 and PAX3-FOXO1, and identify new therapeutic opportunities for children with fusion-driven rhabdomyosarcoma.
Gene Signature
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • SOX10 (SRY-Box 10) • NEUROG1 (Neurogenin 1) • PAX3 (Paired Box 3)
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ERBB3 expression • ERBB3 mutation • PAX3-FOXO1 fusion
13d
The impact of HER3 dynamics on the efficacy of HER3-DXd, a novel HER3 directed antibody-drug conjugate (AACR 2023)
HER3-DXd, a novel antibody-drug conjugate (ADC) composed of a human anti-HER3 IgG1 monoclonal antibody (patritumab) covalently linked to a topoisomerase I inhibitor payload (DXd), is currently being studied in clinical trials for breast cancer and NSCLC...NSCLC cell lines harboring EGFR activating mutations, ROS1 fusions, or ALK fusions were used to evaluate the effect of osimertinib, lorlatinib, or ceritinib on cell surface HER3 expression and payload release (osimertinib only). HER3-DXd was rapidly transferred to early endosomes after binding to HER3... HER3 expression was dynamically changed by HER3-DXd dosing regimen and by RTKi treatment, resulting in a substantial impact on payload release. These findings support our strategy of clinical studies using HER3-DXd after drugs that increase HER3 expression including EGFR TKI and indicate that HER3 dynamics may play a key role in achieving optimal efficacy of HER3-DXd.
Clinical
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EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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EGFR mutation • EGFR expression • ALK fusion • ERBB3 expression • ROS1 fusion • ERBB3 mutation
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Tagrisso (osimertinib) • Lorbrena (lorlatinib) • Zykadia (ceritinib) • patritumab deruxtecan (U3-1402) • patritumab (U3-1287)
25d
Disulfiram/Cu Kills and Sensitizes BRAF-Mutant Thyroid Cancer Cells to BRAF Kinase Inhibitor by ROS-Dependently Relieving Feedback Activation of MAPK/ERK and PI3K/AKT Pathways. (PubMed, Int J Mol Sci)
BRAF, the most common genetic alteration, has become a major therapeutic target in thyroid cancer. Mechanistically, DSF/Cu sensitizes BRAF-mutant thyroid cancer cells to PLX4032 by inhibiting HER3 and AKT in an ROS-dependent way and subsequently relieving feedback activation of MAPK/ERK and PI3K/AKT pathways. This study not only implies potential clinical use of DSF/Cu in cancer therapy but also provides a new therapeutic strategy for BRAF-mutated thyroid cancers.
Journal
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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BRAF mutation • ERBB3 mutation
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Zelboraf (vemurafenib) • disulfiram
1m
EMB-01 in Combination With Osimertinib in Patients With EGFR Mutant Lung Cancer (clinicaltrials.gov)
P1/2, N=115, Not yet recruiting, Shanghai EpimAb Biotherapeutics Co., Ltd. | Initiation date: Oct 2022 --> Jun 2023
Trial initiation date • Combination therapy • Metastases
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation • ERBB3 mutation
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Tagrisso (osimertinib) • bafisontamab (EMB-01)
2ms
Neratinib in Treating Older Patients With Stage IV HER2-Positive Breast Cancer (clinicaltrials.gov)
P2, N=25, Completed, City of Hope Medical Center | Active, not recruiting --> Completed | Trial completion date: Dec 2022 --> Sep 2022
Trial completion • Trial completion date • Metastases
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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HER-2 positive • HER-2 negative • HER-2 L755S • HER-2 A775_G776insYVMA • HER-2 S310F • HER-2 V777L • HER-2 L755P • HER-2 S310Y • ERBB3 mutation • HER-2 G778_P780dup • HER-2 D769Y • HER-2 L869R • HER-2 V842I • ERBB3 V659E • HER-2 G778_S779insCPG • HER-2 L755_T759del • HER-2 A775 • HER-2 D769H • HER-2 R678Q • HER-2 R896C • HER-2 YVMA • ERBB3 L755S
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Nerlynx (neratinib)
3ms
Tumor biomarkers and efficacy in patients treated with trastuzumab emtansine + pertuzumab versus standard of care in HER2-positive early breast cancer: an open-label, phase III study (KRISTINE). (PubMed, Breast Cancer Res)
P3; Although our biomarker analysis did not identify a subgroup of patients that benefited from neoadjuvant T-DM1 + P versus TCH + P, the data revealed that patients with higher HER2 amplification/expression and immune marker levels had improved response irrespective of treatment arm. These analyses confirm the role of HER2 tumor biology and the immune microenvironment in influencing pCR in the neoadjuvant setting and reaffirm the molecular diversity of HER2-positive breast cancer.
Journal • P3 data • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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PD-L1 expression • HER-2 positive • HER-2 amplification • PIK3CA mutation • HER-2 expression • ERBB3 mutation
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Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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carboplatin • docetaxel • Perjeta (pertuzumab) • Kadcyla (ado-trastuzumab emtansine)
3ms
Fusobacterium Nucleatum-Induced Tumor Mutation Burden Predicts Poor Survival of Gastric Cancer Patients. (PubMed, Cancers (Basel))
Survival analysis showed that the combination of Fusobacterium nucleatum infection and high tumor mutation burden formed an extremely effective biomarker to predict poor prognosis. Our results indicated that the ERBB2-PIK3-AKT-mTOR pathway is frequently activated in gastric cancer and that Fusobacterium nucleatum and high mutation burden are strong biomarkers of poor prognosis for gastric cancer patients.
Journal • Tumor mutational burden
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HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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TP53 mutation • TMB-H • HER-2 amplification • PIK3CA mutation • HER-2 mutation • ERBB3 mutation
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TruSight Oncology 500 Assay
3ms
Genomic and immune landscape of ERBB2/ERBB3 alterations in gastroesophageal adenocarcinoma. (ASCO-GI 2023)
ERBB2/ERBB3-alt are associated with significant changes in the tumor microenvironment in GEAC. Co-occurring genetic or immunologic alterations can be exploited to develop effective targeted or immune therapies. >
Tumor mutational burden • MSi-H Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • MSI (Microsatellite instability) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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MSI-H/dMMR • HER-2 mutation • ERBB3 mutation
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Tempus xT Assay
4ms
Targeting the EGF receptor family in non-small cell lung cancer-increased complexity and future perspectives. (PubMed, Cancer Biol Med)
In this subgroup, newer TKIs, such as mobocertinib and the bi-specific antibody amivantamab have recently been approved, whereas less frequent atypical EGFR mutations remain understudied...The recent FDA approval of the antibody-drug conjugate trastuzumab-deruxtecan for pretreated patients with HER2 mutant NSCLC has been an important therapeutic breakthrough. HER3 and HER4 also exert oncogenic potential, and targeted treatment approaches are being developed, particularly for HER3. Overall, strategies to inhibit the oncogenic function of ERBB receptors in NSCLC are currently evolving at an unprecedented pace; therefore, this review summarizes current treatment standards and discusses the outlook for future developments.
Review • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR C797S • ERBB3 mutation
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Enhertu (fam-trastuzumab deruxtecan-nxki) • Rybrevant (amivantamab-vmjw) • Exkivity (mobocertinib)
4ms
Yap governs a lineage-specific neuregulin1 pathway-driven adaptive resistance to RAF kinase inhibitors. (PubMed, Mol Cancer)
YAP activation in thyroid cancer generates a dependency on this transcription factor. YAP governs adaptive resistance to RAF kinase inhibitors and induces a gene expression program in BRAF-mutant cells encompassing effectors in the NRG1 signaling pathway, which play a central role in the insensitivity to MAPK inhibitors in a lineage-dependent manner. HIPPO pathway inactivation serves as a lineage-dependent rheostat controlling the magnitude of the adaptive relief of feedback responses to MAPK inhibitors in BRAF- cancers.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NRG1 (Neuregulin 1)
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BRAF mutation • ERBB3 mutation
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Zelboraf (vemurafenib) • lapatinib • Visudyne (verteporfin) • doxycycline
4ms
A machine learning (ML) approach for identifying genetic biomarkers and new targets associated with impaired survival of breast cancer patients (EBCC 2022)
Our MLF has identified various genes involved in the process of PI3K/Akt and cell adhesion and migration as being critically related to an impaired survival. This methodology should be validated in other genetics datasets. Various of these genes should be investigated as potential new drug discovery targets.
Clinical • Tumor Mutational Burden
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TMB (Tumor Mutational Burden) • FGFR2 (Fibroblast growth factor receptor 2) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • IL7R (Interleukin 7 Receptor) • CSF1R (Colony stimulating factor 1 receptor) • L1CAM (L1 cell adhesion molecule) • PDGFB (Platelet Derived Growth Factor Subunit B) • COL6A2 (Collagen Type VI Alpha 2 Chain) • ITGB5 (Integrin Subunit Beta 5)
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TMB-H • FGFR2 mutation • ERBB3 mutation
4ms
Genetic heterogeneity of liver cancer stem cells. (PubMed, Anat Cell Biol)
The present study provides genetic heterogeneity depending on the surface markers for LCSCs. The genetic heterogeneity of LCSCs should be considered in the development of LCSC-targeting therapeutics.
Journal
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ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • BAP1 (BRCA1 Associated Protein 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD133 • EPCAM (Epithelial cell adhesion molecule) • CD24 (CD24 Molecule) • KRT19 (Keratin 19) • THY1 (Thy-1 membrane glycoprotein) • IRF2 (Interferon Regulatory Factor 2) • ANPEP (Alanyl Aminopeptidase, Membrane)
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BAP1 mutation • CTNNB1 mutation • ERBB3 mutation • CD33 positive • CD133 positive
4ms
Histopathologic Grading Is of Prognostic Significance in Primary Angiosarcoma of Breast: Proposal of a Simplified 2-tier Grading System. (PubMed, Am J Surg Pathol)
Based on 2-tier system, the 5-year overall survival was 38% for high-grade angiosarcoma and 74% for low-grade angiosarcoma. PIK3CA mutations alone or concurrent with KDR alterations were identified in angiosarcomas with worse prognosis.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • KDR (Kinase insert domain receptor)
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PIK3CA mutation • ERBB3 mutation • KDR mutation
5ms
Pertuzumab Plus Trastuzumab in Patients With Colorectal Cancer With ERBB2 Amplification or ERBB2/3 Mutations: Results From the TAPUR Study. (PubMed, JCO Precis Oncol)
Although P + T treatment does not appear to have antitumor activity in CRC with ERBB2/3 mutations, this combination has antitumor activity in patients with CRC with ERBB2 amplification and warrants further study.
Clinical Trial,Phase II • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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HER-2 amplification • HER-2 mutation • ERBB3 mutation
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Herceptin (trastuzumab) • Perjeta (pertuzumab)
5ms
Epigenetic Landscape Predicts Overall Survival and Remission Duration in Adult Acute Myeloid Leukemia (ASH 2022)
HMM expression found that opposing chromatin states, with a more closed (C1) or open (C4) chromatin, significantly affected prognosis. Moreover, the epigenetic landscape was useful to predict OS and RD: compact chromatin equals high OS and RD (C1), and a loose one means poor OS and RD (C4), whereas an intermediary state (C2/C3) leads to average OS and RD. The expression pattern of the worst OS group showed high activation of specific signaling pathways which could be targeted to improve OS and RD.
Clinical
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TP53 (Tumor protein P53) • FLT3 (Fms-related tyrosine kinase 3) • NPM1 (Nucleophosmin 1) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • SRSF2 (Serine and arginine rich splicing factor 2) • WT1 (WT1 Transcription Factor) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • CD34 (CD34 molecule)
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TP53 mutation • NPM1 mutation • RUNX1 mutation • SRSF2 mutation • ERBB3 mutation
5ms
Biomarker Analysis from a Phase II Alternating Therapy with Osimertinib and Afatinib for EGFR-Mutated NSCLC (WJOG10818L) (IASLC-ACLC 2022)
Alternating therapy with osimertinib and afatinib for treatment-naïve patients with EGFR-mutated advanced NSCLC demonstrated encouraging efficacy. The advantages of this therapy are prevention of acquired resistance via secondary EGFR mutations, including T790M and C797S, and a broadened efficacy against various compound EGFR mutations.
P2 data
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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)
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EGFR mutation • HER-2 amplification • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • MET amplification • EGFR C797S • ERBB3 mutation • ERBB3 amplification • EGFR E709G
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AVENIO ctDNA Surveillance Kit
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Tagrisso (osimertinib) • Gilotrif (afatinib)
5ms
Three-dimensional fractal dimension and lacunarity features may noninvasively predict TERT promoter mutation status in grade 2 meningiomas. (PubMed, PLoS One)
3D FD and lacunarity may be useful imaging biomarkers for predicting TERTp mutation status in grade 2 meningiomas.
Journal
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TERT (Telomerase Reverse Transcriptase)
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ERBB3 mutation • TERT mutation • TERT promoter mutation
5ms
A Study of TAS0728 in Patients With Solid Tumors With HER2 or HER3 Abnormalities (clinicaltrials.gov)
P1/2, N=19, Terminated, Taiho Oncology, Inc. | Active, not recruiting --> Terminated; The study was stopped due to unacceptable toxicity during the dose-escalation portion (Phase 1) of the study and did not progress to Phase 2
Trial termination • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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HER-2 amplification • HER-2 overexpression • ERBB3 overexpression • ERBB3 mutation
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TAS0728
6ms
Gene expression and mutation profiles in HER2-mutated metastatic breast cancer (SABCS 2022)
The MutHER, SUMMIT, and PlasmaMATCH clinical trials have shown neratinib monotherapy or neratinib plus fulvestrant combination produce clinical benefit in 28% to 46% in HER2-mutated MBC patients, but median progression-free survival was only 3.6 to 5.4 months. Real-world data show increased HER2 mRNA expression in both HER2- mut and HER2-amps MBC patients. Co-occurring genomic alterations were different among all three groups. Notably, ERBB3 and CDH1 alterations co-occurred commonly in HER2-mut MBC patients, while ESR1 alterations co-occurred in only 4.8%.
HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TOP2A (DNA topoisomerase 2-alpha) • CDK12 (Cyclin dependent kinase 12) • CDH1 (Cadherin 1)
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HER-2 amplification • HER-2 negative • HER-2 mutation • HER-2 expression • CDK12 mutation • ERBB3 mutation • CDH1 mutation
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Tempus xT Assay
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Nerlynx (neratinib) • fulvestrant
6ms
Trial primary completion date • Combination therapy • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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KRAS mutation • EGFR mutation • HER-2 amplification • EGFR amplification • ERBB3 mutation • ERBB4 mutation
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Mekinist (trametinib) • Ibrance (palbociclib) • everolimus • Nerlynx (neratinib)
6ms
MasterKey-01: A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
P1/2, N=91, Terminated, Black Diamond Therapeutics, Inc. | Completed --> Terminated; The development of BDTX-189 was discontinued by the sponsor.
Trial termination • HER2 exon 20 • Metastases
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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EGFR mutation • HER-2 amplification • HER-2 overexpression • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • HER-2 L755S • HER-2 exon 20 insertion • HER-2 V777L • EGFR exon 20 mutation • ERBB3 mutation • HER-2 V842I • HER-2 R678Q • HER-2 exon 23 mutation
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tuxobertinib (BDTX-189)
6ms
MasterKey-01: A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors. (clinicaltrials.gov)
P1/2, N=91, Completed, Black Diamond Therapeutics, Inc. | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Sep 2022 | Trial primary completion date: Jun 2023 --> Sep 2022
Trial completion • Trial completion date • Trial primary completion date • HER2 exon 20
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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EGFR mutation • HER-2 amplification • HER-2 overexpression • EGFR L858R • EGFR exon 19 deletion • EGFR exon 20 insertion • HER-2 L755S • HER-2 exon 20 insertion • HER-2 V777L • EGFR exon 20 mutation • ERBB3 mutation • HER-2 V842I • HER-2 R678Q • HER-2 exon 23 mutation
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tuxobertinib (BDTX-189)
6ms
P21-activated kinase 2-mediated β-catenin signaling promotes cancer stemness and osimertinib resistance in EGFR-mutant non-small-cell lung cancer. (PubMed, Oncogene)
We additionally observed that the suppression of PAK2 via knockdown or pharmacological targeting with PAK inhibitors markedly restored the response of osimertinib-resistant NSCLC cells to osimertinib both in vitro and in vivo. In conclusion, these results indicated that the PAK2-mediated activation of β-catenin is important for osimertinib resistance and targeting the HER3/PAK2/β-catenin pathway has potential therapeutic value in NSCLCs with acquired resistance to osimertinib.
Journal
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EGFR (Epidermal growth factor receptor) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • PAK2 (P21 (RAC1) Activated Kinase 2)
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EGFR mutation • EGFR T790M • ERBB3 mutation
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Tagrisso (osimertinib)
7ms
HERTHENA-Lung02: A Randomized Phase 3 Study of Patritumab Deruxtecan vs Platinum-Based Chemotherapy in Locally Advanced or Metastatic EGFR-Mutated NSCLC After Progression with a Third-Generation EGFR TKI (IASLC-NACLC 2022)
Pts are randomized 1:1 to receive either HER3-DXd 5.6 mg/kg every 3 weeks or 4 cycles of PBC containing pemetrexed (can be continued as maintenance) with cisplatin or carboplatin. Pts are stratified by prior 3rd-gen EGFR TKI treatment (osimertinib vs other), line of prior 3rd-gen EGFR TKI use (first vs second line), region (Asia vs rest of world), and presence of stable brain metastases (yes vs no)...Enrollment began May 2022 and is ongoing, with sites in the US, Canada, EU, Asia, and Australia. This trial in progress was previously presented at ESMO 2022.
Clinical • P3 data
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • ERBB3 expression • ERBB3 mutation
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cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • patritumab deruxtecan (U3-1402) • patritumab (U3-1287)
7ms
Integrated driver mutations profile of chinese gastrointestinal-natural killer/T-cell lymphoma. (PubMed, Front Oncol)
Also, we explored the association between the common mutant genes and immune infiltration. Our aim is that our exploration of these genomic changes will aid in the discovery of new biomarkers and therapeutic targets for those with GI-NKTCL, and finally provide a theoretical basis for improving the treatment and prognosis of patients with GI-NKTCL.
Journal
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TP53 (Tumor protein P53) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • TNFA (Tumor Necrosis Factor-Alpha) • ARID1B (AT-Rich Interaction Domain 1B) • POT1 (Protection of telomeres 1)
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TP53 mutation • ERBB3 mutation
7ms
New P2 trial
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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HER-2 positive • EGFR mutation • HER-2 amplification • HER-2 overexpression • HER-2 negative • ERBB3 mutation • ERBB4 mutation
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Keytruda (pembrolizumab) • paclitaxel • Nerlynx (neratinib)
7ms
Genomic landscape analysis of ERBB3-mutated human cancers reveals common co-occurrence with activating ERBB2 alterations (ECP 2022)
ERBB3 mutations are potential driver alterations with no FDA-approved therapy. A significant proportion of activating ERBB3 mutations co-occur with activating ERBB2 alterations sug-gesting synergistic tumourigenic effects. Our work highlights the importance of broad genomic testing to detect ERBB3 mutations, as these may identify patients potentially responsive to ERBB2 inhibition or antibody-mediated targeting of ERBB3.
EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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EGFR mutation • HER-2 mutation • ERBB3 mutation
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MSK-IMPACT
8ms
EMB-01 in Combination With Osimertinib in Patients With EGFR Mutant Lung Cancer (clinicaltrials.gov)
P1/2, N=115, Not yet recruiting, Shanghai EpimAb Biotherapeutics Co., Ltd.
New P1/2 trial • Combination therapy
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation • ERBB3 mutation
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Tagrisso (osimertinib) • bafisontamab (EMB-01)
8ms
HERTHENA-Lung02: A randomized phase III study of patritumab deruxtecan vs platinum-based chemotherapy in locally advanced or metastatic EGFR-mutated NSCLC after progression with a third-generation EGFR TKI (ESMO 2022)
Pts are randomized 1:1 to receive either HER3-DXd 5.6 mg/kg every 3 weeks or 4 cycles of PBC containing pemetrexed (can be continued as maintenance) with cisplatin or carboplatin. Pts are stratified by prior 3rd-gen EGFR TKI treatment (osimertinib vs other), line of prior 3rd-gen EGFR TKI use (first vs second line), region (Asia vs rest of world), and presence of stable brain metastases (yes vs no)...Other secondary endpoints include investigator-assessed PFS, objective response rate, duration of response, clinical benefit rate, disease control rate, time to response (all per BICR per RECIST v1.1), safety, and patient-reported outcomes. Enrollment into the trial is starting in Q2 2022.
Clinical • P3 data
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • ERBB3 expression • ERBB3 mutation
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cisplatin • Tagrisso (osimertinib) • carboplatin • pemetrexed • patritumab deruxtecan (U3-1402) • patritumab (U3-1287)
8ms
Pharmacokinetics, efficacy, and safety of patritumab deruxtecan (HER3-DXd) in EGFR inhibitor-resistant, EGFR-mutated (EGFRm) non-small cell lung cancer (NSCLC) (ESMO 2022)
The primary objective of cohort 4 is to evaluate the PK of this formulation during the first treatment cycle. Secondary objectives include the evaluation of PK, safety, tolerability, immunogenicity, and efficacy.
Clinical • PK/PD data
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR overexpression • ERBB3 expression • EGFR L861Q • EGFR G719X • ERBB3 overexpression • ERBB3 mutation
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patritumab deruxtecan (U3-1402) • patritumab (U3-1287)
9ms
Molecular vulnerabilities and therapeutic resistance in hormone receptor positive and HER2 dependent breast cancer tumours. (PubMed, Cancer Drug Resist)
Activating HER2 alterations, JNK pathway, hyperactivated TORC1, co-mutations in HER2 and HER3, phenotypic changes of HER2, and few other advanced findings are identified as potential therapeutic targets in treating current HER2 endocrine therapy-resistant tumour. Along with the HER2-focused resistance mechanisms, we also describe how the microbiome may play a role in breast cancer therapy and its potential for new therapeutic strategies to overcome drug resistance in breast cancers.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • CRTC1 (CREB Regulated Transcription Coactivator 1)
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HR positive • HER-2 amplification • ERBB3 mutation
9ms
Combined analysis of receptor expression reflects inter-and intra-tumor heterogeneity in HR+/HER2+ breast cancer. (PubMed, Breast Cancer Res Treat)
This study furthers our understanding of the complexity of tumor heterogeneity in HR+/HER2+ breast cancer, and suggests that the combined analysis of ERBB2 and ESR1 expression may contribute to identifying patients with specific subtypes in this population.
Journal
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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)
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HER-2 positive • ER positive • HR positive • PIK3CA mutation • HER-2 mutation • HER-2 expression • EGFR positive • ERBB3 mutation • ER expression
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Prosigna™ Breast Cancer Prognostic Gene Signature Assay
9ms
Identification of biomarkers of response to a novel HER3-directed antibody drug conjugate (ADC) using breast cancer (BC) patient-derived xenografts (PDX) models (EACR 2022)
TP53-mutant, basal-like PDX models were more likely to show long-term responses to HER3-DXd than luminal B PDX models. Compared to irinotecan, HER3-DXd induced improved antitumor activity inducing higher and persistent levels of S-phase DNA damage.
Clinical • IO biomarker
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TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • MDM2 (E3 ubiquitin protein ligase) • RAD51 (RAD51 Homolog A) • GRB7 (Growth Factor Receptor Bound Protein 7) • MAPT (Microtubule Associated Protein Tau)
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TP53 mutation • ERBB3 expression • ERBB3 overexpression • ERBB3 mutation • TP53 expression
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Prosigna™ Breast Cancer Prognostic Gene Signature Assay
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irinotecan • patritumab deruxtecan (U3-1402)
10ms
Liver Endothelium Promotes HER3-mediated Cell Survival in Colorectal Cancer with Wild-type and Mutant KRAS. (PubMed, Mol Cancer Res)
Moreover, we determined that blocking HER3, either by siRNA knockdown or the humanized antibody seribantumab, blocked EC-induced colorectal cancer survival in vitro in both KRAS wild-type and mutant colorectal cancer cells, and the HER3 antibody seribantumab significantly decreased colorectal cancer tumor growth and sensitized tumors to chemotherapy in an orthotopic xenograft model with colorectal cancer tumors developed in the liver. In summary, our findings demonstrated that blocking HER3 had significant effects on attenuating liver EC-induced CRC cell survival independent of the KRAS mutation status. Implications: This body of work highlighted a potential strategy of using HER3 antibodies in combination with standard chemotherapy agents for treating patients with either KRAS wild-type or KRAS mutant mCRC.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3)
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KRAS mutation • KRAS wild-type • RAS wild-type • ERBB3 mutation
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seribantumab (MM-121)