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DRUG CLASS:

HER4 inhibitor

7d
Exploring tyrosine kinase inhibitors for HER2-positive breast cancer: comprehensive review on a complete pharmacology-molecular mechanisms, safety profiles, and insights from preclinical and clinical studies. (PubMed, Clin Transl Oncol)
They have demonstrated substantial improvements in survival-free and life expectancy of patients, establishing them as a standard treatment modality. The ongoing development of novel tyrosine kinase inhibitors and their strategic integration into personalized treatment regimens will shape the evolving landscape of breast cancer therapy.
Preclinical • Review • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive
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lapatinib • Nerlynx (neratinib) • Irene (pyrotinib)
12d
Integrated Multi-omic Profiling Identifies BRD8/EP400 as a Pivotal Chromatin Module Mediating Anti-HER2 Response in HR+/HER2+ Breast Cancer. (PubMed, Cancer Res)
BRD8 regulated ER-dependent and independent growth pathways, and depletion of BRD8 abolished neratinib-induced ER activation and restored drug sensitivity in resistant cells. A 3-gene BRD8 signature successfully predicted anti-HER2 therapy response in two human clinical trials. Together, these findings establish BRD8 as both a predictive biomarker for anti-HER2 response and a therapeutic target to overcome resistance in HR+/HER2+ breast cancer.
Journal
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ER (Estrogen receptor) • EP400 (E1A Binding Protein P400)
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HER-2 positive • HR positive • HR positive + HER-2 positive
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Nerlynx (neratinib)
22d
Pyrotinib or placebo in combination with trastuzumab and docetaxel for HER2 positive metastatic breast cancer: long term survival results from randomised phase 3 PHILA trial. (PubMed, BMJ)
The updated analysis of the phase 3 PHILA trial confirmed the superiority of pyrotinib in combination with trastuzumab and docetaxel over placebo in combination with trastuzumab and docetaxel in sustaining longer progression-free survival and improving overall survival for initial treatment of HER2 positive metastatic breast cancer. The safety profile remained consistent with interim findings, with no new safety signals identified during extended follow-up. This analysis reinforces the efficacy of this dual anti-HER2 (pyrotinib plus trastuzumab) regimen as an effective treatment strategy for this patient population.
Clinical • P3 data • Journal
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive • EGFR positive
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Herceptin (trastuzumab) • docetaxel • Irene (pyrotinib)
25d
New trial • Real-world evidence
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive
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Herceptin (trastuzumab) • Perjeta (pertuzumab) • Irene (pyrotinib)
26d
Genomic profiling and HER2-targeted therapy: a case series of Chinese salivary duct carcinoma patients and its clinical implications. (PubMed, Front Oncol)
Two metastatic SDC patients with HER2 amplification responded to HER2 tyrosine kinase inhibitor (TKI) pyrotinib and the combination of trastuzumab and pertuzumab, respectively. Our work underscores the potential of genomic profiling to guide precision therapy in SDC, with HER2-targeted treatments offering promising therapeutic avenues.
Journal
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • HRAS (Harvey rat sarcoma viral oncogene homolog) • NF1 (Neurofibromin 1)
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TP53 mutation • HER-2 amplification • PIK3CA mutation
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Herceptin (trastuzumab) • Perjeta (pertuzumab) • Irene (pyrotinib)
26d
Trial of Pre-operative Neratinib and Endocrine Therapy With Trastuzumab in ER-Positive, HER-2 Positive Breast Cancers (clinicaltrials.gov)
P2, N=30, Recruiting, Ruth O'Regan | Trial completion date: Jan 2026 --> Jul 2027 | Trial primary completion date: Dec 2025 --> Jun 2026
Trial completion date • Trial primary completion date
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HER-2 (Human epidermal growth factor receptor 2) • ER (Estrogen receptor) • PGR (Progesterone receptor)
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HER-2 positive • ER positive • PGR positive
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Herceptin (trastuzumab) • Nerlynx (neratinib) • letrozole • anastrozole
1m
Identification of prognostic genes associated with tolerogenic dendritic cells in gastric cancer based on transcriptomic data. (PubMed, PLoS One)
The present study revealed five prognostic genes and constructed a predictive model, which provided a theoretical basis for the correlation linking Tolerogenic dendritic cells to gastric cancer, and established potential therapeutic strategies in managing gastric cancer. Single-cell analysis revealed that INHBA, ASCL2, and CD36 exhibited marked differential expression in dendritic cells.
Journal
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CD36 (thrombospondin receptor) • CXCL1 (Chemokine (C-X-C motif) ligand 1) • RNASE1 (Ribonuclease A Family Member 1) • ASCL2 (Achaete-Scute Family BHLH Transcription Factor 2)
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Gilotrif (afatinib)
1m
EAY131-A: Testing Afatinib as Potentially Targeted Treatment in Cancers With EGFR Genetic Changes (MATCH - Subprotocol A) (clinicaltrials.gov)
P2, N=19, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Dec 2025 --> Jan 2027
Trial completion date
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EGFR (Epidermal growth factor receptor)
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EGFR mutation • EGFR L858R • EGFR L861Q • EGFR S768I
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Gilotrif (afatinib)
1m
Advances in the study of pyrotinib for the treatment of HER2-positive breast cancer. (PubMed, Breast Cancer Res)
Moreover, its ability to traverse the blood-brain barrier confers potential therapeutic advantages in patients with brain metastases. This comprehensive review provides a systematic overview of the pharmacological profile and mechanism of action of pyrotinib, with emphasis on recent clinical trials assessing pyrotinib-based regimens in HER2-positive breast cancer.
Review • Journal
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ERBB4 (erb-b2 receptor tyrosine kinase 4)
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HER-2 positive
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Irene (pyrotinib)
1m
Prospective Observational Real-World Study of Afatinib as First-Line Treatment in Patients with Epidermal Growth Factor Receptor (EGFR) Mutation-Positive Advanced Non-Small Cell Lung Cancer (NSCLC) in China. (PubMed, Lung Cancer (Auckl))
No new safety concerns were found. This study provides real-world evidence of the effectiveness and safety of afatinib as first-line therapy for Chinese patients with EGFR mutation-positive advanced NSCLC.
Observational data • Journal • Real-world evidence
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EGFR (Epidermal growth factor receptor)
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EGFR mutation
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Gilotrif (afatinib)
2ms
NCI-2017-00831: Poziotinib in EGFR Exon 20 Mutant Advanced NSCLC (clinicaltrials.gov)
P2, N=93, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2027 --> Feb 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Feb 2026; <75% participation
Trial completion date • Trial termination • Trial primary completion date
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
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EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation
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FoundationOne® CDx • Guardant360® CDx • cobas® EGFR Mutation Test v2 • therascreen® EGFR RGQ PCR Kit
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Pozenveo (poziotinib)
2ms
New P2 trial
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HER-2 (Human epidermal growth factor receptor 2)
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HER-2 positive
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Herceptin (trastuzumab) • Enhertu (fam-trastuzumab deruxtecan-nxki) • capecitabine • Irene (pyrotinib) • trastuzumab rezetecan (SHR-A1811)