MET/HGF co-targeting in pancreatic cancer: A tool to provide insight into the tumor/stroma crosstalk

Chiara Modica, Dora Tortarolo, Paolo M. Comoglio, Cristina Basilico, Elisa Vigna

Research output: Contribution to journalReview article

1 Citation (Scopus)

Abstract

The ‘onco-receptor’ MET (Hepatocyte Growth Factor Receptor) is involved in the activation of the invasive growth program that is essential during embryonic development and critical for wound healing and organ regeneration during adult life. When aberrantly activated, MET and its stroma-secreted ligand HGF (Hepatocyte Growth Factor) concur to tumor onset, progression, and metastasis in solid tumors, thus representing a relevant target for cancer precision medicine. In the vast majority of tumors, wild-type MET behaves as a ‘stress-response’ gene, and relies on ligand stimulation to sustain cancer cell ‘scattering’, invasion, and protection form apoptosis. Moreover, the MET/HGF axis is involved in the crosstalk between cancer cells and the surrounding microenvironment. Pancreatic cancer (namely, pancreatic ductal adenocarcinoma, PDAC) is an aggressive malignancy characterized by an abundant stromal compartment that is associated with early metastases and resistance to conventional and targeted therapies. Here, we discuss the role of the MET/HGF axis in tumor progression and dissemination considering as a model pancreatic cancer, and provide a proof of concept for the application of dual MET/HGF inhibition as an adjuvant therapy in pancreatic cancer patients.

Original languageEnglish
Article number3920
JournalInternational Journal of Molecular Sciences
Volume19
Issue number12
DOIs
Publication statusPublished - Dec 1 2018

Fingerprint

Hepatocyte Growth Factor
Crosstalk
crosstalk
Pancreatic Neoplasms
Tumors
tumors
cancer
Neoplasms
Cells
metastasis
Proto-Oncogene Proteins c-met
Ligands
progressions
therapy
Medicine
wound healing
Cell death
ligands
Genes
Chemical activation

Keywords

  • HGF
  • MET
  • Metastasis
  • Pancreatic cancer
  • Target therapy
  • Tumor microenvironment

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

Cite this

MET/HGF co-targeting in pancreatic cancer : A tool to provide insight into the tumor/stroma crosstalk. / Modica, Chiara; Tortarolo, Dora; Comoglio, Paolo M.; Basilico, Cristina; Vigna, Elisa.

In: International Journal of Molecular Sciences, Vol. 19, No. 12, 3920, 01.12.2018.

Research output: Contribution to journalReview article

Modica, Chiara ; Tortarolo, Dora ; Comoglio, Paolo M. ; Basilico, Cristina ; Vigna, Elisa. / MET/HGF co-targeting in pancreatic cancer : A tool to provide insight into the tumor/stroma crosstalk. In: International Journal of Molecular Sciences. 2018 ; Vol. 19, No. 12.
@article{4da6140724de45d787ab3eebd9e04421,
title = "MET/HGF co-targeting in pancreatic cancer: A tool to provide insight into the tumor/stroma crosstalk",
abstract = "The ‘onco-receptor’ MET (Hepatocyte Growth Factor Receptor) is involved in the activation of the invasive growth program that is essential during embryonic development and critical for wound healing and organ regeneration during adult life. When aberrantly activated, MET and its stroma-secreted ligand HGF (Hepatocyte Growth Factor) concur to tumor onset, progression, and metastasis in solid tumors, thus representing a relevant target for cancer precision medicine. In the vast majority of tumors, wild-type MET behaves as a ‘stress-response’ gene, and relies on ligand stimulation to sustain cancer cell ‘scattering’, invasion, and protection form apoptosis. Moreover, the MET/HGF axis is involved in the crosstalk between cancer cells and the surrounding microenvironment. Pancreatic cancer (namely, pancreatic ductal adenocarcinoma, PDAC) is an aggressive malignancy characterized by an abundant stromal compartment that is associated with early metastases and resistance to conventional and targeted therapies. Here, we discuss the role of the MET/HGF axis in tumor progression and dissemination considering as a model pancreatic cancer, and provide a proof of concept for the application of dual MET/HGF inhibition as an adjuvant therapy in pancreatic cancer patients.",
keywords = "HGF, MET, Metastasis, Pancreatic cancer, Target therapy, Tumor microenvironment",
author = "Chiara Modica and Dora Tortarolo and Comoglio, {Paolo M.} and Cristina Basilico and Elisa Vigna",
year = "2018",
month = "12",
day = "1",
doi = "10.3390/ijms19123920",
language = "English",
volume = "19",
journal = "International Journal of Molecular Sciences",
issn = "1661-6596",
publisher = "MDPI AG",
number = "12",

}

TY - JOUR

T1 - MET/HGF co-targeting in pancreatic cancer

T2 - A tool to provide insight into the tumor/stroma crosstalk

AU - Modica, Chiara

AU - Tortarolo, Dora

AU - Comoglio, Paolo M.

AU - Basilico, Cristina

AU - Vigna, Elisa

PY - 2018/12/1

Y1 - 2018/12/1

N2 - The ‘onco-receptor’ MET (Hepatocyte Growth Factor Receptor) is involved in the activation of the invasive growth program that is essential during embryonic development and critical for wound healing and organ regeneration during adult life. When aberrantly activated, MET and its stroma-secreted ligand HGF (Hepatocyte Growth Factor) concur to tumor onset, progression, and metastasis in solid tumors, thus representing a relevant target for cancer precision medicine. In the vast majority of tumors, wild-type MET behaves as a ‘stress-response’ gene, and relies on ligand stimulation to sustain cancer cell ‘scattering’, invasion, and protection form apoptosis. Moreover, the MET/HGF axis is involved in the crosstalk between cancer cells and the surrounding microenvironment. Pancreatic cancer (namely, pancreatic ductal adenocarcinoma, PDAC) is an aggressive malignancy characterized by an abundant stromal compartment that is associated with early metastases and resistance to conventional and targeted therapies. Here, we discuss the role of the MET/HGF axis in tumor progression and dissemination considering as a model pancreatic cancer, and provide a proof of concept for the application of dual MET/HGF inhibition as an adjuvant therapy in pancreatic cancer patients.

AB - The ‘onco-receptor’ MET (Hepatocyte Growth Factor Receptor) is involved in the activation of the invasive growth program that is essential during embryonic development and critical for wound healing and organ regeneration during adult life. When aberrantly activated, MET and its stroma-secreted ligand HGF (Hepatocyte Growth Factor) concur to tumor onset, progression, and metastasis in solid tumors, thus representing a relevant target for cancer precision medicine. In the vast majority of tumors, wild-type MET behaves as a ‘stress-response’ gene, and relies on ligand stimulation to sustain cancer cell ‘scattering’, invasion, and protection form apoptosis. Moreover, the MET/HGF axis is involved in the crosstalk between cancer cells and the surrounding microenvironment. Pancreatic cancer (namely, pancreatic ductal adenocarcinoma, PDAC) is an aggressive malignancy characterized by an abundant stromal compartment that is associated with early metastases and resistance to conventional and targeted therapies. Here, we discuss the role of the MET/HGF axis in tumor progression and dissemination considering as a model pancreatic cancer, and provide a proof of concept for the application of dual MET/HGF inhibition as an adjuvant therapy in pancreatic cancer patients.

KW - HGF

KW - MET

KW - Metastasis

KW - Pancreatic cancer

KW - Target therapy

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=85058376821&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85058376821&partnerID=8YFLogxK

U2 - 10.3390/ijms19123920

DO - 10.3390/ijms19123920

M3 - Review article

C2 - 30544501

AN - SCOPUS:85058376821

VL - 19

JO - International Journal of Molecular Sciences

JF - International Journal of Molecular Sciences

SN - 1661-6596

IS - 12

M1 - 3920

ER -