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Related Experiment Video

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CCN-Based Therapeutic Peptides Modify Pancreatic Ductal Adenocarcinoma Microenvironment and Decrease Tumor Growth in

Andrea Resovi1, Patrizia Borsotti1, Tommaso Ceruti2

  • 1Laboratory of Tumor Microenvironment, Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, 24126 Bergamo, Italy.

Cells
|April 17, 2020
PubMed
Summary

New peptides targeting CCN2 show promise in treating pancreatic cancer by reducing tumor growth and improving chemotherapy effectiveness. These CCN3-derived peptides remodel the tumor microenvironment, offering a novel therapeutic strategy for pancreatic ductal adenocarcinoma (PDAC).

Keywords:
CCN2/CCN3PDACmatricellular proteinstumor microenvironment

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Area of Science:

  • Oncology
  • Cancer Biology
  • Drug Discovery

Background:

  • Pancreatic ductal adenocarcinoma (PDAC) features a dense desmoplastic stroma, hindering chemotherapy and promoting tumor progression.
  • CCN2/CTGF, a profibrotic protein, is abundant in the PDAC microenvironment and linked to poor prognosis.

Purpose of the Study:

  • To evaluate the therapeutic potential of BLR100 and BLR200, synthetic peptides targeting CCN2, in a murine PDAC model.
  • To investigate the effects of these peptides on the tumor microenvironment and their efficacy in combination with gemcitabine.

Main Methods:

  • Administration of BLR100 and BLR200 peptides as monotherapy and in combination with gemcitabine in an orthotopic murine PDAC model.
  • Assessment of tumor growth, microenvironment characteristics (fibrosis, vascularization, necrosis), ascites formation, and gemcitabine pharmacokinetics.

Main Results:

  • Both peptides demonstrated dose-dependent tumor inhibitory activity and reduced fibrosis, neovascularization, and necrosis.
  • Peptides effectively prevented ascites formation and showed enhanced efficacy when combined with gemcitabine.
  • Improved combination efficacy was not solely due to increased gemcitabine delivery, suggesting microenvironmental modulation.

Conclusions:

  • CCN3-derived peptides BLR100 and BLR200 exhibit therapeutic value in PDAC by targeting CCN2-mediated pathways.
  • These peptides beneficially remodel the tumor stroma, supporting their potential as a novel therapeutic strategy for pancreatic cancer.