Targeting HGF/c-MET Axis in Pancreatic Cancer

• Published in: International journal of molecular sciences 2020-12, Vol.21 (23), p.9170
• Main Authors: Pothula, Srinivasa P, Xu, Zhihong, Goldstein, David, Pirola, Romano C, Wilson, Jeremy S, Apte, Minoti V
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Animals; Biomarkers, Tumor; c-Met protein; Cancer therapies; Cell adhesion & migration; Cell growth; Collagen; Colorectal cancer; Cytokines; Cytotoxicity; Endothelial cells; Extracellular matrix; Gene Expression Regulation, Neoplastic; Growth factors; Hepatocyte growth factor; Hepatocyte Growth Factor - genetics; Hepatocyte Growth Factor - metabolism; Humans; Kinases; Ligands; Lymphocytes; Medical prognosis; Metastases; Metastasis; Neoplasm Staging; Neovascularization, Pathologic; Pancreatic cancer; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - etiology; Pancreatic Neoplasms - metabolism; Pancreatic Neoplasms - therapy; Patients; Phosphorylation; Proteins; Proto-Oncogene Proteins c-met - genetics; Proto-Oncogene Proteins c-met - metabolism; Review; Signal Transduction; Stellate cells; Stromal cells; Tumor Microenvironment; Tumors; Vascular endothelial growth factor; Wound healing
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21239170

Pancreatic cancer (pancreatic ductal adenocarcinoma (PDAC/PC)) has been an aggressive disease that is associated with early metastases. It is characterized by dense and collagenous desmoplasia/stroma, predominantly produced by pancreatic stellate cells (PSCs). PSCs interact with cancer cells as well as other stromal cells, facilitating disease progression. A candidate growth factor pathway that may mediate this interaction is the hepatocyte growth factor (HGF)/c-MET pathway. HGF is produced by PSCs and its receptor c-MET is expressed on pancreatic cancer cells and endothelial cells. The current review discusses the role of the MET/HGF axis in tumour progression and dissemination of pancreatic cancer. Therapeutic approaches that were developed targeting either the ligand (HGF) or the receptor (c-MET) have not been shown to translate well into clinical settings. We discuss a two-pronged approach of targeting both the components of this pathway to interrupt the stromal-tumour interactions, which may represent a potential therapeutic strategy to improve outcomes in PC.