MET Inhibition in Non-Small Cell Lung Cancer

Abstract

Cancer treatment paradigms have evolved over recent years with an emphasis on personalised medicine. Targeted agents are being used to improve treatment outcomes and quality of life. For the treatment of non-small cell lung cancer, several agents with unique genetic and epigenetic targets are available. To this extent, mesenchymal–epithelial transition (MET), a heterodimer receptor tyrosine kinase involved in embryogenesis and organogenesis, has been investigated as a potential target for biological agents. MET dysregulation can occur via different mechanisms and trigger tumourigenesis and disease spread. Besides driving the oncogenic dependence of cells, MET is also involved in acquired resistance to epidermal growth factor receptor inhibitors. As such, many small molecule kinase inhibitors and antibodies have been developed or are currently in different phases of clinical trials to counteract the MET-induced neoplastic activity. Some of these agents are selective while others are nonselective with multiple other potential targets. This article aims to present an overview of biological functioning of MET, its role in oncogenesis and resistance to treatment, and clinical studies evaluating MET inhibitors for treatment of non-small cell lung cancer.

Keywords

• hepatocyte growth factor (hgf)
• mesenchymal–epithelial transition (met)
• met inhibitors
• non-small cell lung cancer (nsclc)