Targeting HGF/c-MET Axis in Pancreatic Cancer |
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| Authors: | Srinivasa P Pothula Zhihong Xu David Goldstein Romano C Pirola Jeremy S Wilson Minoti V Apte |
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| Affiliation: | 1.Pancreatic Research Group, South Western Sydney Clinical School, Faculty of Medicine and Ingham Institute for Applied Medical Research, Liverpool, NSW 2170, Australia; (S.P.P.); (Z.X.); (R.C.P.); (J.S.W.);2.Faculty of Medicine, The University of New South Wales, Sydney, NSW 2052, Australia; |
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| Abstract: | 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. |
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| Keywords: | HGF-c-MET Pancreatic Cancer Stromal-tumour interactions |
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