The EGF receptor (EGFR) HER3 is emerging as an attractive cancer therapeutic target due to its central position in the HER receptor signaling network. HER3 amplifies phosphoinositide 3-kinase (PI3K)-driven tumorigenesis and its upregulation in response to other anti-HER therapies has been implicated in resistance to them. Here, we report the development and characterization of RG7116, a novel a...

Purpose: Dual blockade of HER2 with trastuzumab and lapatinib or with pertuzumab is a superior treatment approach compared with single-agent HER2 inhibitors. However, many HER2-overexpressing breast cancers still escape from this combinatorial approach. Inhibition of HER2 and downstream phosphoinositide 3-kinase (PI3K)/AKT causes a transcriptional and posttranslational upregulation of HER3 whic...

EGFR, HER2, and HER3 contribute to the initiation and progression of human cancers, and are therapeutic targets for monoclonal antibodies and tyrosine kinase inhibitors. An important source of resistance to these agents arises from functional redundancy among EGFR, HER2, and HER3. EGFR family members contain conserved extracellular structures that are stabilized by disulfide bonds. Compounds th...

SOLTI TOT-HER3 study (NCT04610528) previously reported the biologic and clinical activity of HER3-DXd, a HER3 directed antibody drug conjugate, across first 30 patients (Prat A, SABCS 2021). Here, we present efficacy safety results all in initial cohort. This window opportunity, multicenter, pre-operative trial enrolled with untreated HR+/HER2- operable (≥1 cm) breast cancer (BC). Patients were...

The HER family of receptor tyrosine kinases, including EGF receptor (EGFR), HER2, HER3, and HER4, transduce growth-promoting signals in response to ligand binding to their extracellular domains (ECD). This family is deregulated in numerous cancers, with mutations in EGFR and HER2 often serving as "driver" events to activate key growth factor signaling pathways such as the RAS-ERK and PI3K-AKT p...

BACKGROUND The human epidermal growth factor receptor 3 (HER3) is an ErbB/HER family member that dimerizes with other ErbB receptors such as HER2. Numerous agents against HER3 are in clinical development despite variable data for the prognostic impact of HER3 expression. Here we report a meta-analysis of the association of HER3 expression and survival in solid tumors. METHODS PubMed was searc...

Human epidermal growth factor receptor 3 (HER3) is closely involved in tumor progression and is an important target of therapy. To evaluate the prognostic significance of HER3 in malignant solid tumors, we searched the PUBMED, EMBASE and CNKI databases for relevant studies written in English or Chinese up to December 2015. Fifteen studies comprising 2964 patients were identified. The HER3+ rate...

HER2/HER3 dimerization resulting from overexpression of HER2 or neuregulin (NRG1) in cancer leads to HER3-mediated oncogenic activation of phosphoinositide 3-kinase (PI3K) signaling. Although ligand-blocking HER3 antibodies inhibit NRG1-driven tumor growth, they are ineffective against HER2-driven tumor growth because HER2 activates HER3 in a ligand-independent manner. In this study, we describ...

The human EGFR family consists of four type-1 transmembrane tyrosine kinase receptors: HER1 (EGFR, ErbB1), HER2 (Neu, ErbB2), HER3 (ErbB3), and HER4 (ErbB4). HER3 can dimerize with EGFR, HER2 and even c-Met and likely plays a central role in the response to EGFR-targeted therapy. Because HER3 lacks significant kinase activity and cannot be inhibited by tyrosine kinase inhibitors, neutralizing a...

Aberrant expression and activation of EGFR and ERBB2 (HER2) have been successfully targeted for cancer therapeutics. Recent evidence from both basic and clinical studies suggests that ERBB3 (HER3) serves as a key activator of downstream signaling through dimerization with other ERBB proteins and plays a critical role in the widespread clinical resistance to EGFR and HER2 targeting cancer therap...