Zeitschrift für molekulare Biomarker und Diagnose

Mechanisms of Trastuzumab Resistance and Opportunities to Overcome Therapeutic Resistance

Abstract

Milos Dokmanovic and Wen Jin Wu

Trastuzumab is a humanized monoclonal antibody directed against extracellular domain IV of Human Epidermal Growth Factor Receptor 2 (HER2) and is approved for the treatment of HER2-positive breast cancers either alone or in combination with chemotherapeutic agents [1,2]. HER2 is a member of HER/ErbB family of receptor tyrosine kinases, which play important role in breast cancer development and progression [1]. HER2 is overexpressed in approximately 20-30% of invasive breast cancer and is associated with poor disease-free survival and poor response to chemotherapy [3-5]. Over the past two decades, the development of monoclonal antibodies targeting HER2 has been intensely pursued as important cancer therapeutic strategy. While treatment with trastuzumab very successfully improves outcomes for women with HER2-positive breast cancer, therapeutic resistance to trastuzumab, including primary and acquired resistance, pose a significant hurdle in the treatment of HER2-positive breast cancers [2,6,7], Better understanding of molecular mechanisms underlying primary or acquired resistance to trastuzumab is critical to improving the survival of patients with HER2-positive breast cancer.