Recent Progress and Advances in HGF/MET-Targeted Therapeutic Agents for Cancer Treatment

Abstract

The hepatocyte growth factor (HGF): MET axis is a ligand-mediated receptor tyrosine kinase pathway that is involved in multiple cellular functions, including proliferation, survival, motility, and morphogenesis. Aberrancy in the HGF/MET pathway has been reported in multiple tumor types and is associated with tumor stage and prognosis. Thus, targeting the HGF/MET pathway has become a potential therapeutic strategy in oncology development in the last two decades. A number of novel therapeutic agents—either as therapeutic proteins or small molecules that target the HGF/MET pathway—have been tested in patients with different tumor types in clinical studies. In this review, recent progress in HGF/MET pathway-targeted therapy for cancer treatment, the therapeutic potential of HGF/MET-targeted agents, and challenges in the development of such agents will be discussed.

Prognostic Role of c-Met Overexpression in High Grade Glioma: a Meta-analysis

“…With the rising of molecular biology and gene engineering, combinatorial treatments which target different molecular pathways and mechanisms is expected to improve the way we cure and diagnose this horrible disease 24 . The HGF/MET signaling pathway is one of expected signal ways 25, 26 . c-Met and its only ligand, hepatocyte growth factor (HGF), have been proved to be connected with many physiological and pathological processes 27 .…”

Assessment of pharmacokinetic interaction between rilotumumab and epirubicin, cisplatin and capecitabine (ECX) in a Phase 3 study in gastric cancer

“…Over the past two decades, the hepatocyte growth factor (HGF):MET pathway has been shown to control important cellular functions such as proliferation and survival and to play a critical role in tumour development and metastasis [3][4][5][6][7][8][9][10][11]. A number of antagonists that target this pathway have been evaluated as potential anticancer drugs.…”

89Zr-DFO-AMG102 Immuno-PET to Determine Local Hepatocyte Growth Factor Protein Levels in Tumors for Enhanced Patient Selection

“…Because subjects have been evaluated by different methods in various studies-such as serum levels of HGF protein, local levels of MET protein in tumors (overexpression), and gene amplification (not always accompanied by transcriptional upregulation and overexpression of protein products)-finding appropriate autocrine HGF/MET cancer types and corresponding models is challenging (25). To our knowledge, patient selection for clinical trials of HGF-targeted drugs has not been attempted by measuring HGF levels directly in tumors, and although increased circulating HGF may be a prognostic factor in many cancers, it may be the wrong parameter to evaluate when investigating HGF-targeting therapies (25). No tools currently exist to noninvasively determine the levels of HGF present in the local tumor environment.…”