HER2/neu, a Mr 185,000 tyrosine kinase receptor that is overexpressed in breast cancer, undergoes proteolytic cleavage of its extracellular domain (ECD). In contrast with other membrane-bound proteins, including growth factor receptors, that are cleaved by a common machinery system, we show that HER2 cleavage is a slow process and is not activated by protein kinase C. Pervanadate, a general inh...

IMPORTANCE OF THE FIELD Differential levels of HER2 expression in normal versus HER2-overexpressing breast carcinomas, together with the demonstration of a key role for HER2 in tumor progression, make HER2 an ideal target for specific therapeutic approaches. AREAS COVERED IN THIS REVIEW This review considers the clinical value of trastuzumab and lapatinib, the two HER2-targeted therapies appr...

PURPOSE Preclinical studies in HER2-amplified gastrointestinal cancer models have shown that cotargeting HER2 with a monoclonal antibody and a small molecule is superior to monotherapy with either inhibitor, but the underlying cooperative mechanisms remain unexplored. We investigated the molecular underpinnings of this synergy to identify key vulnerabilities susceptible to alternative therapeut...

Background: Breast cancer is the most common cancer in females in the UK and has greater severity in patients who overexpress human epidermal growth receptor 2 (HER2) proteins in the breast tissue. Trastuzumab is a humanised monoclonal antibody and is targeted towards blocking the HER2 pathway and effectively reduces the recurrence of breast cancer and associated mortality. However, trastuzumab...

BACKGROUND Our objective was to compare 111In- or 64Cu-DOTA-trastuzumab Fab fragments for imaging small or large s.c. tumor xenografts in athymic mice that display a wide range of human epidermal growth factor receptor-2 (HER2) expression using microSPECT/CT or microPET/CT. METHODS Trastuzumab Fab were labeled with 111In or 64Cu by conjugation to 1,4,7,10-tetraazacyclododecane N, N', N'', N''...

Currently, only patients with HER2-positive tumors are candidates for HER2-targeted therapies. However, recent clinical observations suggest that the survival of patients with HER2-low breast cancers, who lack HER2 amplification, may benefit from adjuvant therapy that targets HER2. In this study, we explored a mechanism through which these benefits may be obtained. Prompted by the hypothesis th...

The overexpression of HER2/neu and EGFR receptors plays important roles in tumorigenesis and tumor progression. Targeting these two receptors simultaneously can have a more widespread application in early diagnosis of cancers. In this study, a new multifunctional nanoparticles (MnMEIO-CyTE777-(Bis)-mPEG NPs) comprising a manganese-doped iron oxide nanoparticle core (MnMEIO), a silane-amino func...

Polychemotherapy combined with trastuzumab (T) or pertuzumab (TP) is a standard preoperative systemic treatment in patients HER2-positive breast cancer. In Poland T reimbursed according to the Drug Prescription Program of Ministry Health (MoH) for primary tumors bigger than 1cm independently from nodal status, whereas TP 2 cm positive lymph node(s) lack hormonal receptors expression. The does n...

OBJECTIVE Changes in ER, PR and Her2 receptor status between primary and metastatic cancer tissue have been suggested in breast cancer. The frequencies of these changes are still not fully understood. The purpose of this study was to evaluate these changes in breast cancer population of Kuwait. SUBJECTS AND METHOD Changes in the biological features between primary and recurrent disease in 70 ...

Purpose: In breast cancer, the EGF receptors host an increasing number of therapeutic targets and the interactive mechanisms of actions of the receptors and their ligands justify investigation of the EGF family as an entity. Experimental design: Paired tissue samples of normal breast tissue and primary breast carcinomas were examined in a prospective study of 163 patients. A third sample was ob...