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https://wslhd.intersearch.com.au/wslhdjspui/handle/1/8176
Title: | HGF/c-Met pathway inhibition combined with chemotherapy increases cytotoxic T-cell infiltration and inhibits pancreatic tumour growth and metastasis |
Authors: | Mekapogu, A. R.;Xu, Z.;Pothula, S.;Perera, C.;Pang, Tony;Hosen, S. M. Z.;Damalanka, V.;Janetka, J.;Goldstein, D.;Pirola, R.;Wilson, J.;Apte, M. |
WSLHD Author: | Pang, Tony |
Issue Date: | 2023 |
Citation: | Cancer Letters 568:216286, 2023 |
Abstract: | Pancreatic cancer (PC) is a deadly cancer with a high mortality rate. The unique characteristics of PC, including desmoplasia and immunosuppression, have made it difficult to develop effective treatment strategies. Pancreatic stellate cells (PSCs) play a crucial role in the progression of the disease by interacting with cancer cells. One of the key mediators of PSC - cancer cell interactions is the hepatocyte growth factor (HGF)/c-MET pathway. Using an immunocompetent in vivo model of PC as well as in vitro experiments, this study has shown that a combined approach using HGF/c-MET inhibitors to target stromal-tumour interactions and chemotherapy (gemcitabine) to target cancer cells effectively decreases tumour volume, EMT, and stemness, and importantly, eliminates metastasis. Notably, HGF/c-MET inhibition decreases TGF-beta secretion by cancer cells, resulting in an increase in cytotoxic T-cell infiltration, thus contributing to cancer cell death in tumours. HGF/c-MET inhibition + chemotherapy was also found to normalise the gut microbiome and improve gut microbial diversity. These findings provide a strong platform for assessment of this triple therapy (HGF/c-MET inhibition + chemotherapy) approach in the clinical setting. |
URI: | https://wslhd.intersearch.com.au/wslhdjspui/handle/1/8176 |
DOI: | https://dx.doi.org/10.1016/j.canlet.2023.216286 |
Journal: | Cancer Letters |
Type: | Journal Article |
Study or Trial: | Research Support, Non-U.S. Gov't |
Facility: | Westmead |
Keywords: | Hepatocyte Growth Factor Proto-Oncogene Proteins c-met Cell Line, Tumor Pancreatic Neoplasms T-Lymphocytes |
Appears in Collections: | Westmead Hospital 2019 - 2024 |
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