BACKGROUND Activating EGFR mutations, HER2, and HER3 are implicated in lung cancer; however, with the exception of EGFR gene amplification in lung adenocarcinoma harboring EGFR mutations, their involvement in disease progression during the early stages is poorly understood. In this paper, we focused on which receptor is correlated with lung adenocarcinoma progression in the presence or absence ...

Human epidermal growth factor receptor family members (EGFR, HER2, HER3, and HER4) play important roles in tumorigenesis and response to cancer therapeutics. In this study, we evaluated the capacity of the dual-target antibody MEHD7945A that simultaneously targets EGFR and HER3 to modulate radiation response in lung and head and neck cancer models. Antitumor effects of MEHD7945A in combination ...

HER3-DXd and trastuzumab deruxtecan (T-DXd) are antibody-drug-conjugates (ADCs) directed against HER3 HER2, respectively. Both drugs have shown efficacy in patients (pt) with HR+/HER2- BC. Baseline protein or mRNA levels do not predict from HER3-DXd. Here, we aimed to evaluate the association of early response HER2 levels. TOT-HER3 (NCT04610528), a window-of-opportunity trial, evaluated single ...

Published studies on the association between human epidermal factor receptor 3 (HER3) expression and overall survival (OS) in gastrointestinal cancers have yielded conflicting results. The aim of this study was to explore the association of HER3 over-expression with OS in gastrointestinal cancers. A systematic search was performed through Medline/PubMed, Embase, Science Direct and Elsevier. The...

The importance of HER2/HER3 signaling in decreasing the effects of lung injury was recently demonstrated. Transgenic mice unable to signal through HER2/HER3 had significantly less bleomycin-induced pulmonary fibrosis and showed a survival benefit. Based on these data, we hypothesized that pharmacological blockade of HER2/HER3 in vivo in wild-type mice would have the same beneficial effects. We ...

AIM Resistance to trastuzumab (which is a standard therapy for breast cancer patients with HER2 overexpression) is associated with higher risk of progression or cancer death, and might be related to activation of signalling cascades (PI3K/AKT/mTOR, Ras/Raf/MAPK) and decreased level of their inhibitors. MATERIAL AND METHODS Formalin-fixed paraffin-embedded tumour specimens from 118 HER2-overex...

Human MENA(11a) (hMENA(11a)), an epithelial-associated isoform of the actin binding protein enabled homolog (ENAH, also known as mammalian ENA [MENA]), is upregulated and phosphorylated following the activation of human epidermal growth factor receptor (HER) 1, HER2, and HER3. Here, we reveal a novel role of this isoform in sustaining cell survival and propose hMENA(11a) as a marker of HER3 act...

We describe here the existence of a heregulin-HER3 autocrine loop, and the contribution of heregulin-dependent, HER2-mediated HER3 activation to gefitinib insensitivity in non-small cell lung cancer (NSCLC). ADAM17 protein, a major ErbB ligand sheddase, is upregulated in NSCLC and is required not only for heregulin-dependent HER3 signaling, but also for EGFR ligand-dependent signaling in NSCLC ...

The human epidermal growth factor receptor 3 (HER3) has in recent years been recognized as a key node in the complex signaling network of many different cancers. It is implicated in de novo and acquired resistance against therapies targeting other growth factor receptors, e.g., EGFR, HER2, and it is a major activator of the PI3K/Akt signaling pathway. Consequently, HER3 has attracted substantia...

Background Although cytotoxic CD8 T lymphocytes (CTL) were historically considered primary effectors of antitumor immunity, solely boosting CTL responses with CD8 vaccines in various tumor types has yielded unpredictable clinical results, possibly because CTLs function suboptimally without adequate CD4 T lymphocyte help. CD4 T-helper type 1 (Th1) cells secrete INF-g/TNF-a, inducing tumor senesc...