HER3 plays a key oncogenic role in breast cancer, being associated with poor prognosis and resistance to PI3K/AKT/mTOR inhibitors (inh) endocrine therapy (ET). HER3-DXd is an anti-HER3 monoclonal antibody conjugated topoisomerase I inh by peptide-based cleavable linker, which showed activity HER3-expressing ABC (NCT02980341). ICARUS-BREAST01 (NCT04965766) ongoing multi-center, single-arm, phase...

Background: Solid tumors and rheumatoid arthritis have overlapping mechanisms of pathogenesis. Both diseases are characterized by a hyperproliferative component, hypoxia, excessive angiogenesis, inflammation. First-line treatments also overlap. Examples methotrexate cyclophosphamide which used to treat many different malignancies as well being first-line for arthritis. The component RA is the p...

Poorly-differentiated colorectal cancers (PD-CRC) show high metastatic potential and poor prognosis. However, molecular characteristics of PD-CRC remain unknown to date, particularly in molecular targeting therapy for patients with PD-CRC. In this study, we examined the expression of EGFR, HER2 and HER3 in PD-CRC by immunohistochemical analysis of archived clinical specimens of primary tumors a...

BACKGROUND AND AIM Human epidermal growth factor receptor (HER) family plays an important role in gastric cancer (GC), especially HER2. Too much attention has been paid to HER2; however, the functions of HER3 and HER4 overexpression in GC are always ignored. The clinicopathological and prognostic roles of HER3 and HER4 in GC are controversial. In this study, a systematic review and meta-analysi...

BACKGROUND The pathogenesis of penile squamous cell carcinoma (PSCC) is not well understood, though risk factors include human papillomavirus (HPV). Disruption of HER/PTEN/Akt pathway is present in many cancers; however there is little information on its function in PSCC. We investigated HER family receptors and phosphatase and tension homolog (PTEN) in HPV-positive and negative PSCC and its im...

Abstract BACKGROUND Leptomeningeal disease (LMD) occurs in approximately 5% of patients with breast cancer and has a median survival 2-4 months. We found loss the anti-HER2 anti-HER3 CD4 Th1 immune responses patients. In pre-clinical clinical trials, administration class II HER2 peptide-pulsed dendritic cell vaccine (HER2-DCV) partially restores pathologic complete HER2+ Here, we examined intra...

We examined the effects of LJM716, an HER3 (ERBB3) neutralizing antibody that inhibits ligand-induced and ligand-independent HER3 dimerization, as a single agent and in combination with BYL719, an ATP competitive p110α-specific inhibitor, against HER2-overexpressing breast and gastric cancers. Treatment with LJM716 reduced HER2-HER3 and HER3-p85 dimers, P-HER3 and P-AKT, both in vitro and in vi...

BACKGROUND Although heregulin and human epidermal growth factor receptor 3 (HER3) are frequently expressed at high levels in patients with head and neck cancer, their prognostic value remains unclear. The authors explored the prognostic significance of heregulin/HER3 expression in patients with oropharyngeal squamous cell carcinoma (OPSCC), taking into account other HER family members as well a...

We are interested in the signaling between axons and glia that leads to myelination and maintenance of the myelin internode, and we have focused on the role of neuregulins and their receptors. Neuregulins are a family of ligands that includes heregulin, neu differentiation factor, glial growth factor, and the acetylcholine receptor-inducing activity. Three signal transducing transmembrane recep...

The requisite role of HER3 in HER2-amplified cancers is beyond what would be expected as a dimerization partner or effector substrate and it exhibits a substantial degree of resiliency that mitigates the effects of HER2-inhibitor therapies. To better understand the roots of this resiliency, we conducted an in-depth chemical-genetic interrogation of the signaling network downstream of HER3. A un...