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BIOMARKER:

HER-2 mutation

i
Other names: ERBB2, CD340, HER-2, HER2, NEU, NGL, V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2
Entrez ID:
Related tests:
16h
Targeted and shallow whole genome sequencing identifies therapeutic opportunities in p53abn endometrial cancers. (PubMed, Clin Cancer Res)
sWGS and targeted sequencing identified therapeutic opportunities in 75% of p53abn EC patients. Further research is needed to determine the efficacy of treatments targeting these identified pathways within p53abn ECs.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • HRD (Homologous Recombination Deficiency) • CCNE1 (Cyclin E1) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • PPP2R1A (Protein Phosphatase 2 Scaffold Subunit Aalpha)
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TP53 mutation • BRCA2 mutation • BRCA1 mutation • HER-2 overexpression • HER-2 amplification • PIK3CA mutation • HER-2 mutation • HRD • MYC amplification • CCNE1 amplification • HRD + BRCA1 mutation • HRD signature
1d
DESTINY-LUNG02: Trastuzumab Deruxtecan in Participants With HER2-mutated Metastatic Non-small Cell Lung Cancer (NSCLC) (clinicaltrials.gov)
P2, N=152, Active, not recruiting, Daiichi Sankyo | Trial completion date: Mar 2024 --> Aug 2024
Trial completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation
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Enhertu (fam-trastuzumab deruxtecan-nxki)
4d
Exemestane plus everolimus and palbociclib in metastatic breast cancer: clinical response and genomic/transcriptomic determinants of resistance in a phase I/II trial. (PubMed, Nat Commun)
Multi-omics data from the phase IIa patients (n = 24 tumor/17 blood biopsy exomes; n = 27 tumor transcriptomes) showed potential mechanisms of resistance (convergent evolution of HER2 activation, BRAFV600E), identified joint genomic/transcriptomic resistance features (ESR1 mutations, high estrogen receptor pathway activity, and a Luminal A/B subtype; ERBB2/BRAF mutations, high RTK/MAPK pathway activity, and a HER2-E subtype), and provided hypothesis-generating results suggesting that mTOR pathway activation correlates with response to the trial's therapy. Our results illustrate how genome and transcriptome sequencing may help better identify patients likely to respond to CDK4/6i therapies.
P1/2 data • Clinical Trial,Phase I • Clinical Trial,Phase II • Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor)
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BRAF V600E • BRAF V600 • HER-2 mutation • ER mutation • ESR1 mutation
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Ibrance (palbociclib) • everolimus • exemestane
4d
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)
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TP53 mutation • HER-2 mutation • MYC amplification • ERBB3 mutation
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MSK-IMPACT
6d
Discovery of Novel 5,6-Dihydro-4H-pyrido[2,3,4-de]quinazoline Irreversible Inhibitors Targeting Both Wild-Type and A775_G776insYVMA Mutated HER2 Kinases. (PubMed, J Med Chem)
The derivatives with the pyrido[2,3,4-de]quinazoline core displayed superior efficacy of antiproliferation in BaF3 cells harboring HER2insYVMA mutation compared with afatinib and neratinib. Oral administration of 4a and 10e (30 mg/kg, QD) displayed significant antitumor efficacy in an in vivo xenograft model. We proposed promising strategies for the development of HER2insYVMA mutant inhibitors in this study.
Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation • HER-2 A775 • HER-2 YVMA
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Gilotrif (afatinib) • Nerlynx (neratinib)
9d
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
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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)
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HER-2 mutation • CD8 expression • ERBB3 mutation • CDH1 expression • CDH1 mutation • CTLA4 expression
13d
A Study of Mobocertinib in Japanese Adults With Non-Small Cell Lung Cancer (clinicaltrials.gov)
P1, N=53, Active, not recruiting, Takeda | Trial completion date: Mar 2024 --> Mar 2025
Trial completion date
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR L858R • HER-2 mutation • EGFR exon 19 deletion • EGFR exon 20 insertion • EGFR A763_Y764insFQEA • EGFR exon 20 mutation
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Exkivity (mobocertinib)
13d
Enrollment change • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • AR (Androgen receptor)
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HER-2 positive • HER-2 amplification • HER-2 mutation • AR positive
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trastuzumab rezetecan (SHR-A1811) • leuprolide acetate for depot suspension • Airui'en (rezvilutamide) • SHR-A1921
13d
SYNERGY-AI: Artificial Intelligence Based Precision Oncology Clinical Trial Matching and Registry (clinicaltrials.gov)
P=N/A, N=50000, Recruiting, Massive Bio, Inc. | Trial completion date: Jun 2025 --> Jun 2027 | Trial primary completion date: Dec 2024 --> Dec 2026
Trial completion date • Trial primary completion date
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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) • ER (Estrogen receptor) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • FLT3 (Fms-related tyrosine kinase 3) • ABL1 (ABL proto-oncogene 1) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • FGFR2 (Fibroblast growth factor receptor 2) • PTEN (Phosphatase and tensin homolog) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • BCL2 (B-cell CLL/lymphoma 2) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • STK11 (Serine/threonine kinase 11) • NPM1 (Nucleophosmin 1) • HRAS (Harvey rat sarcoma viral oncogene homolog) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • CLDN18 (Claudin 18) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • JAK2 (Janus kinase 2) • NRG1 (Neuregulin 1) • POLE (DNA Polymerase Epsilon) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PD-1 (Programmed cell death 1) • CCND1 (Cyclin D1) • MCL1 (Myeloid cell leukemia 1) • KDR (Kinase insert domain receptor) • PBRM1 (Polybromo 1) • BAP1 (BRCA1 Associated Protein 1) • VEGFA (Vascular endothelial growth factor A) • BCL6 (B-cell CLL/lymphoma 6) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • PTCH1 (Patched 1) • FGFR4 (Fibroblast growth factor receptor 4) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MAP2K2 (Mitogen-activated protein kinase kinase 2) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • WT1 (WT1 Transcription Factor) • ATRX (ATRX Chromatin Remodeler) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • TSC2 (TSC complex subunit 2) • BRCA (Breast cancer early onset) • CHEK2 (Checkpoint kinase 2) • PD-L2 (Programmed Cell Death 1 Ligand 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • JAK1 (Janus Kinase 1) • FANCA (FA Complementation Group A) • TSC1 (TSC complex subunit 1) • MDM4 (The mouse double minute 4) • POLD1 (DNA Polymerase Delta 1) • CDK6 (Cyclin-dependent kinase 6) • CEBPA (CCAAT Enhancer Binding Protein Alpha) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • AURKA (Aurora kinase A) • JAK3 (Janus Kinase 3) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2) • CHEK1 (Checkpoint kinase 1) • GATA6 (GATA Binding Protein 6) • MSH3 (MutS Homolog 3) • TGFBR2 (Transforming Growth Factor Beta Receptor 2) • GNAS (GNAS Complex Locus) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor) • AKT2 (V-akt murine thymoma viral oncogene homolog 2) • CCND2 (Cyclin D2) • CCND3 (Cyclin D3) • CSF1R (Colony stimulating factor 1 receptor) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • ERCC4 (ERCC Excision Repair 4, Endonuclease Catalytic Subunit) • HDAC1 (Histone Deacetylase 1) • PRDM1 (PR/SET Domain 1) • ZNF217 (Zinc Finger Protein 217) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • GATA3 (GATA binding protein 3) • PARP2 (Poly(ADP-Ribose) Polymerase 2) • PARP3 (Poly(ADP-Ribose) Polymerase Family Member 3) • SDHA (Succinate Dehydrogenase Complex Flavoprotein Subunit A) • ACVR1B (Activin A Receptor Type 1B) • ZNF703 (Zinc Finger Protein 703)
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HER-2 mutation • BAP1 mutation • AKT1 mutation • FGFR3 fusion • JAK3 mutation
14d
The application of HER2-ADC in future: More than expression. (PubMed, Med)
We identified specific mutations, notably G776delinsVC, that are associated with higher therapeutic response rates, suggesting a refined approach for precision treatment. Further validation and exploration are crucial for potential breakthroughs in ADC therapy.
Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation
16d
Trial completion date • Trial primary completion date • HER2 exon 20 • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • HER-2 mutation
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BAY 2927088
16d
SUMMIT: Basket Study of Neratinib in Participants With Solid Tumors Harboring Somatic HER2 or EGFR Exon 18 Mutations (clinicaltrials.gov)
P2, N=582, Terminated, Puma Biotechnology, Inc. | Completed --> Terminated; The study was terminated to align with the sponsor's current development plans for neratinib. The decision was not based on any new efficacy or safety data for neratinib.
Trial termination • Pan tumor
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • HER-2 negative • HER-2 mutation • EGFR exon 18 mutation
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Herceptin (trastuzumab) • paclitaxel • Nerlynx (neratinib) • fulvestrant
21d
New P2 trial • Combination therapy
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation • HER-2 exon 20 insertion • HER-2 L755S • HER-2 exon 20 mutation • HER-2 YVMA • HER-2 exon 23 mutation
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Herceptin (trastuzumab) • docetaxel • Perjeta (pertuzumab)
22d
External beam radiation therapy for recurrent or residual thyroid cancer: What is the best treatment time and the best candidate for long-term local disease control? (PubMed, Head Neck)
Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • RET (Ret Proto-Oncogene) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • TERT (Telomerase Reverse Transcriptase) • FAT1 (FAT atypical cadherin 1)
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BRAF mutation • HER-2 mutation • TERT mutation
22d
Comprehensive molecular and immune profiling of triple negative invasive lobular carcinoma (AACR 2024)
These data suggest that TN-ILC had higher frequency of CDH1, ERBB2, AKT1, ARID1A mutations, higher M2 macrophages and neutrophils and lower M1 macrophages and CD8 T cells infiltration and, lower T cell inflamed signature. High TMB and AR expression can translate into use of immunotherapy (ICI) and AR antagonists in these patients. Additonal analysis to determine the optimal biomarker for ICI response in TN-ILC is needed.
Tumor mutational burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • BCL2 (B-cell CLL/lymphoma 2) • ARID1A (AT-rich interaction domain 1A) • CD8 (cluster of differentiation 8) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • MCL1 (Myeloid cell leukemia 1) • LAG3 (Lymphocyte Activating 3) • KMT2C (Lysine Methyltransferase 2C) • CDH1 (Cadherin 1) • BCL2A1 (BCL2 Related Protein A1) • FOXP3 (Forkhead Box P3) • PMAIP1 (Phorbol-12-Myristate-13-Acetate-Induced Protein 1) • BCL2L10 (BCL2 like 10) • BAK1 (BCL2 Antagonist/Killer 1)
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PD-L1 expression • ER positive • TMB-H • MSI-H/dMMR • HER-2 mutation • ARID1A mutation • BCL2 expression • AKT1 mutation • AR expression
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PD-L1 IHC 22C3 pharmDx • VENTANA PD-L1 (SP142) Assay
22d
First NGS-based companion diagnostic to aid in selecting non-small cell lung cancer patients with ERBB2 (HER2) activating mutations for treatment with trastuzumab deruxtecan (AACR 2024)
The 6 AV studies met the necessary product requirements and acceptance criteria to detect clinical samples with ERBB2 mutations. Additionally, the CV study clinical accuracy and clinical efficacy results demonstrated the safety and effectiveness of the use of the ODxTT in FFPE samples as an aid to identify NSCLC patients eligible for treatment with the Daiichi Sankyo lung cancer therapeutic T-DXd.
Clinical • Next-generation sequencing • Companion diagnostic
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation • MET mutation
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Oncomine™ Dx Target Test • TruSight Tumor 170 Assay
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Enhertu (fam-trastuzumab deruxtecan-nxki)
22d
Tumor genomic heterogeneity in non-small cell lung cancer (NSCLC) patients from Latin America (AACR 2024)
The prevalence of mutations and fusions in the eight most relevant NSCLC genes (EGFR, KRAS, ALK, MET, RET, BRAF, ROS1 and ERBB2) varies based on sociodemographic, clinical and lifestyle characteristics. Clear distinctions emerged in the prevalence of EGFR, KRAS and ERBB2 mutations among the three countries (EGFR: 20.9%, 17.6%, 35.3%; KRAS: 21.8%, 15.6%, 10.3%; ERBB2: 2.8%, 3.3%, 4.4% for Brazil, Chile, and Peru, respectively). Furthermore, distinct association patterns were identified between the prevalence of genetic alterations and the studied factors, with attributes such as sex, tobacco use and ethnicity mostly influencing the occurrence of EGFR, ALK and ROS1 alterations.
Clinical
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
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KRAS mutation • EGFR mutation • HER-2 mutation
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Oncomine Focus Assay
22d
Pan-cancer analysis of the influence of ERBB2 alteration on HER2 expression (AACR 2024)
Introduction: HER2 (ERBB2) is a target for various anti-cancer therapies, including large (Trastuzumab deruxtecan) or small molecules (Neratinib). An AI-powered pan-cancer image analysis of HER2 IHC of tumor cells in conjunction with genomic data reveals a positive correlation between ex20ins and S310x ERBB2 mutation and protein expression. This correlation is also seen at the RNA level, but the lesser levels relative to ERBB2 amplified cases suggests the effect may be mediated at the protein level.
Pan tumor
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 amplification • HER-2 mutation • HER-2 expression • HER-2 YVMA
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PATHWAY antiHer2/neu (4B5) Rabbit Monoclonal Primary Antibody • Lunit SCOPE HER2
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Nerlynx (neratinib) • Enhertu (fam-trastuzumab deruxtecan-nxki)
23d
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
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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 positive • HR positive • HER-2 overexpression • HER-2 mutation • ERBB3 mutation
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Perjeta (pertuzumab) • Enhertu (fam-trastuzumab deruxtecan-nxki)
28d
Genomic drivers in craniopharyngiomas: Analysis of the AACR project GENIE database. (PubMed, Childs Nerv Syst)
CTNNB1 mutations account for a large proportion of somatic mutations in craniopharyngiomas. Identification of specific point mutations and secondary drivers may advance development of novel craniopharyngioma preclinical models for targeted therapy testing.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • BRAF (B-raf proto-oncogene) • KMT2D (Lysine Methyltransferase 2D) • KMT2C (Lysine Methyltransferase 2C) • FANCA (FA Complementation Group A) • ARID1B (AT-Rich Interaction Domain 1B)
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BRAF mutation • HER-2 mutation • ATM mutation • CTNNB1 mutation • FANCA mutation • BLM mutation
28d
A Study of XMT-2056 in Advanced/Recurrent Solid Tumors That Express HER2 (clinicaltrials.gov)
P1, N=162, Recruiting, Mersana Therapeutics | Suspended --> Recruiting | Trial completion date: Nov 2025 --> Apr 2027 | Trial primary completion date: Nov 2025 --> Apr 2027
Enrollment open • Trial completion date • Trial primary completion date • Metastases
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HER-2 amplification • HER-2 mutation • HER-2 expression
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calotatug ginistinag (XMT-2056)
29d
EGFR and ERBB2 Exon 20 Insertion Mutations in Chinese Non-small Cell Lung Cancer Patients: Pathological and Molecular Characterization, and First-Line Systemic Treatment Evaluation. (PubMed, Target Oncol)
EGFR/ERBB2-20ins is more common in early lung adenocarcinoma. EGFR-20ins had more variants. In both cohorts, the results for first-line systemic treatments showed no significant difference.
Journal • EGFR exon 20 • HER2 exon 20
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1)
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TP53 mutation • EGFR mutation • HER-2 mutation • EGFR exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 23 mutation
30d
A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction. (PubMed, World J Surg Oncol)
Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • MUC2 (Mucin 2)
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HER-2 mutation
1m
HER2 phosphorylation induced by TGF-β promotes mammary morphogenesis and breast cancer progression. (PubMed, J Cell Biol)
Increased HER2 S779 phosphorylation is observed in human breast cancers and positively correlated with the activation of HER2, MAPK, and AKT. Our findings demonstrate the crucial role of TGF-β-induced S779 phosphorylation in HER2 activation, mammary gland development, and the pro-oncogenic function of TGF-β in breast cancer progression.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • TGFB1 (Transforming Growth Factor Beta 1)
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HER-2 mutation
1m
Clinical sequencing defines the somatic and germline mutation landscapes of Chinese HER2-Low Breast Cancer. (PubMed, Cancer Lett)
In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA2 (Breast cancer 2, early onset) • GATA3 (GATA binding protein 3)
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BRCA2 mutation • HR positive • HER-2 negative • PIK3CA mutation • HER-2 mutation • GATA3 mutation
1m
Pharmacological insights on novel oral selective estrogen receptor degraders in breast cancer. (PubMed, Eur J Pharmacol)
Fulvestrant is the first approved SERD with proven efficacy and good tolerability in clinical practice...Elacestrant is an orally bioavailable SERD that has been recently approved by the FDA for postmenopausal women with ER+, human epidermal growth factor receptor 2-negative (HER2-), estrogen receptor 1 (ESR1)-mutated advanced or metastatic breast cancer with disease progression following at least one line of endocrine therapy. Other molecules of the same class currently tested in clinical trials are amcenestrant, giredestrant, camizestrant, and imlunestrant. The current review article offers a detailed pharmacological perspective of this emerging drug class, which may help with their possible future clinical applications.
Review • Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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ER positive • HER-2 negative • HER-2 mutation • ESR1 mutation
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fulvestrant • Orserdu (elacestrant) • amcenestrant (SAR439859) • camizestrant (AZD9833) • imlunestrant (LY3484356) • giredestrant (GDC-9545)
1m
Somatic mutations in a multigene panel and impact on prognosis based on TP53 status in Chinese HER2-positive patients undergoing neoadjuvant therapy: A single-institution retrospective cohort. (PubMed, Cancer Med)
The genetic mutation profiles of Chinese HER2+ patients who received NAT were discrepant with respect to HR status or DFS events. TP53 mutations have significant prognostic value in patients with NAT for HER2-positive BC and patients benefit differently depending on HR status, the neoadjuvant regimen and response, which highlights the significance of genetic factors in treatment customization based on individual genetic and clinical characteristics.
Retrospective data • 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) • PGR (Progesterone receptor) • KMT2C (Lysine Methyltransferase 2C)
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HER-2 positive • TP53 mutation • HER-2 mutation • ER negative • PGR negative
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Herceptin (trastuzumab)
1m
Targeted Sequencing in Gastric Cancer: Association with Tumor Molecular Characteristics and FLOT Therapy Effectiveness. (PubMed, Curr Issues Mol Biol)
TP53 mutation and PTEN mutation are associated with changes in factors associated with neoangiogenesis. In concusion, patients who did not have aggressive growth markers that were verified by molecular features had the best response to treatment, including complete morphologic regression.
Journal • PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • PD-1 (Programmed cell death 1)
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PD-L1 expression • HER-2 positive • TP53 mutation • KRAS mutation • PIK3CA mutation • HER-2 mutation • PTEN mutation • PD-1 expression • TP53 expression
1m
CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape. (PubMed, NPJ Breast Cancer)
In conclusion, our work uncovers opportunities for further treatment personalization and stresses the need for effective combination treatments to address the altered tumor genomic landscape following AI+CDK4/6i exposure. Further, we demonstrated the potential of RWD for refining patient treatment strategy and guiding clinical trial design.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • CDK4 (Cyclin-dependent kinase 4)
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HER-2 positive • HR positive • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation • HR positive + HER-2 negative • PTEN mutation + HR positive
1m
US Food and Drug Administration Approval Summary: Elacestrant for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer. (PubMed, J Clin Oncol)
The approval of elacestrant in ER+, HER2- advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.
FDA event • Journal • Metastases
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor)
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ER positive • EGFR mutation • HER-2 negative • HER-2 mutation • ER mutation • ESR1 mutation • EGFR positive
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Orserdu (elacestrant)
1m
Genetic landscape of breast cancer subtypes following radiation therapy: insights from comprehensive profiling. (PubMed, Front Oncol)
Different breast cancer subtypes have their own type-specific mutation patterns. FGFR1 and KLHL6 mutations are protective factors for radiation-induced skin toxicity in breast cancer patients.
Journal
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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) • FGFR1 (Fibroblast growth factor receptor 1) • RAD21 (RAD21 Cohesin Complex Component) • KLHL6 (Kelch Like Family Member 6)
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TP53 mutation • PIK3CA mutation • HER-2 mutation • FGFR1 mutation
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FoundationOne® CDx
1m
Cytomorphology of Non-Small Cell Lung Carcinoma with MET Exon 14 Skipping Mutations (USCAP 2024)
One patient received Capmatinib and one patient Pembrolizumab. This study showed that NSCLC with METex14 are poorly differenciated tumors with necrotic background,multinucleation,atypical mitoses,and pleomorphic/sarcomatoid features. Larger studies are needed to confirm our preliminary findings. Routine NGS testing on cytological specimens is feasible and essential for METex14 testing and select patients with advanced lung NSCLC for targeted therapies.
PD(L)-1 Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • MET (MET proto-oncogene, receptor tyrosine kinase) • NKX2-1 (NK2 Homeobox 1)
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TP53 mutation • HER-2 amplification • HER-2 mutation • MET amplification • MET exon 14 mutation • MET mutation • TP53 amplification
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Oncomine Focus Assay
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Keytruda (pembrolizumab) • Tabrecta (capmatinib)
1m
Next-Generation Sequencing Experience of Colorectal Cancer at a Quebec Health Care Centre (USCAP 2024)
Our study is concordant with larger CRC sequencing studies. Although, the main targetable mutations are covered by the Focus Panel, a considerable proportion of specimens had no identifiable mutations. As more treatments become available, more extensive panels are necessary.
Next-generation sequencing
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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) • MSI (Microsatellite instability) • MLH1 (MutL homolog 1) • PMS2 (PMS1 protein homolog 2)
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KRAS mutation • BRAF mutation • PIK3CA mutation • HER-2 mutation • APC mutation • PMS2 mutation
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Illumina Focus Panel
1m
A Study of BL-M07D1 in Patients With HER2-mutated, Locally Advanced or Metastatic Non-small-cell Lung Cancer (clinicaltrials.gov)
P1/2, N=58, Not yet recruiting, Sichuan Baili Pharmaceutical Co., Ltd. | Trial completion date: Dec 2025 --> Mar 2026 | Initiation date: Dec 2023 --> Mar 2024 | Trial primary completion date: Dec 2025 --> Mar 2026
Trial completion date • Trial initiation date • Trial primary completion date • Metastases
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 mutation
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BL-M07D1
1m
DESTINY-PanTumor01: A Study of T-DXd for the Treatment of Solid Tumors Harboring HER2 Activating Mutations (clinicaltrials.gov)
P2, N=102, Active, not recruiting, AstraZeneca | Trial completion date: Jan 2028 --> Jul 2026
Trial completion date • Metastases
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HER-2 mutation • HER-2 L755S • HER-2 S310F • HER-2 V777L • HER-2 S310Y • HER-2 G778_P780dup • HER-2 D769Y • HER-2 V842I • HER-2 A775 • HER-2 D769H • HER-2 G660D + HER-2 S310F • HER-2 P780-Y781insGSP • HER-2 R678Q • HER-2 T862A • HER-2 YVMA
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Enhertu (fam-trastuzumab deruxtecan-nxki)
2ms
Detection of Tumor DNA in Bronchoscopic Fluids in Peripheral NSCLC: A Proof-of-Concept Study. (PubMed, JTO Clin Res Rep)
Furthermore, in eight of 34 r-EBUS without tumor cells on microscopic examination, we were able to detect the mutation in four paired guide sheath flush supernatant, compared with only two in paired plasma. The detection of tumor DNA in the supernatant of guide sheath flush fluid collected during r-EBUS bronchoscopy represents a sensitive and complementary method for genotyping NSCLC.
Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11)
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KRAS mutation • EGFR mutation • HER-2 mutation
2ms
Recurrence/prognosis estimation using a molecularly positive surgical margin-based model calls for alternative curative strategies in pIIIA/N2 NSCLC. (PubMed, Mol Oncol)
Notably, mutational profiling through broad-panel NGS could more sensitively detect residual tumors than the conventional histologic methods. Adjuvant CT and adjuvant CRT exhibited no significant difference in eliminating locoregional recurrence risk for stage pIIIA/N2 NSCLC patients with molecularly positive surgical margins.
Journal
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HER-2 (Human epidermal growth factor receptor 2) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • TYK2 (Tyrosine Kinase 2) • SMARCD3 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily D, Member 3)
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HER-2 mutation • SMARCA4 mutation
2ms
Age-related and organ-specific host mosaicism as a driver of dormant cancer cell awakening (AACR 2024)
This hypothesis has been explored in clinical trials data where the presence of CH in ER+ and HER2+ metastatic BC patient cohorts (MSK-IMPACT) was associated with the response to first line CDK4/6i/endocrine therapy or taxol/herceptin/pertuzumab, respectively. We also tested whether CH can accelerate dormant DCC awakening in a murine model of CH carrying mutations in DNMT3A (KO or point mutation) and HER2+ mammary cancer. We propose our work may provide unprecedented insights into how a traceable age-related-mosaicism in the bone marrow (CH) may shape distant organs to be drive metastatic relapse.
HER-2 (Human epidermal growth factor receptor 2) • DNMT3A (DNA methyltransferase 1) • ASXL1 (ASXL Transcriptional Regulator 1) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDK4 (Cyclin-dependent kinase 4)
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HER-2 mutation • DNMT3A mutation • ASXL1 mutation • TET2 mutation
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MSK-IMPACT
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Herceptin (trastuzumab) • paclitaxel • Perjeta (pertuzumab)
2ms
AFT-50 EndoMAP: A phase Ib/II multi-cohort study of targeted agents for patients with recurrent or persistent endometrial cancer (SGO 2024)
Approximately, 30% of recurrent EC pts fall into this category. Pairing ICI with targeted therapies carries the potential to elicit prolonged anti-tumor effects. Atezolizumab (Atezo) is a humanized monoclonal PD-L1 inhibitor that has demonstrated monotherapy antitumor activity with an acceptable safety profile in relapsed recurrent EC...In cohort A, pts may be eligible for one of the following doublets: Atezo+ipatasertib (PIK3CA/PTEN/AKT1-altered cancers), Atezo+talazoparib (tumors with genomic loss of heterozygosity (LOH) ≥16%), Atezo+Trastuzumab emtansine (ERBB2/HER2 mutated and/or amplified tumors), and Atezo+Tiragolumab (MSI-H and/or TMB>10 mut/MB). The Atezo+bevacizumab (biomarker unmatched) arm is closed to enrollment...Pts will receive Atezo in addition to the targeted agent (at the study approved dosing schedule) until progression, unacceptable toxicity, pt or physician decision to withdraw from the study, death, or study termination. Pts in cohort B, will be eligible for inavolisib (PIK3CA/PTEN/AKT1-altered cancers) + letrozole. The primary endpoint for Cohort A is confirmed overall response rate (ORR) for each cohort, and for Cohort B is progression free survival at 6 months...As a platform study, additional arms may be added, as supported by evolving understanding of EC and molecular targets. EndoMAP is actively enrolling at 18 sites in the US with a target of 25 sites nationwide.
P1/2 data • Clinical • Tumor mutational burden • PD(L)-1 Biomarker • PARP Biomarker • MSi-H Biomarker • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • AKT1 (V-akt murine thymoma viral oncogene homolog 1)
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MSI-H/dMMR • HER-2 amplification • HER-2 mutation
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FoundationOne® CDx
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Avastin (bevacizumab) • Tecentriq (atezolizumab) • Kadcyla (ado-trastuzumab emtansine) • Talzenna (talazoparib) • letrozole • ipatasertib (RG7440) • inavolisib (GDC-0077) • tiragolumab (RG6058)
2ms
Identification of somatic mutation-driven enhancers and their clinical utility in breast cancer. (PubMed, iScience)
We identified eight candidate drugs such as erastin, colforsin, and STOCK1N-35874 targeting the mutated enhancer. Our findings suggest that somatic mutations contribute to breast cancer subtype progression by altering enhancer activity, which could be potential candidates for cancer therapy.
Journal • BRCA Biomarker
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HER-2 (Human epidermal growth factor receptor 2) • BRCA (Breast cancer early onset) • ALOX15B (Arachidonate 15-Lipoxygenase Type B)
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HER-2 mutation • BRCA mutation
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erastin
2ms
Efficacy of immunotherapy in HER2-mutated non-small cell lung cancer: a single-arm meta-analysis. (PubMed, J Cancer Res Clin Oncol)
ICIs demonstrate promising anti-tumor activity and safety in patients with HER2-mutated NSCLC. Furthermore, the combined regimen of ICIs and chemotherapy may provide a significant therapeutic option for this patient population.
Retrospective data • Review • Journal • IO biomarker
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HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • HER-2 mutation
2ms
Trial completion
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HER-2 overexpression • HER-2 mutation
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anvatabart opadotin (ARX788)