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Functional network analysis reveals potential repurposing of β-blocker atenolol for pancreatic cancer therapy

Adam Hermawan1, Herwandhani Putri2, Rohmad Yudi Utomo3

  • 1Laboratory of Macromolecular Engineering, Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Universitas Gadjah Mada Sekip Utara II, Yogyakarta, 55281, Indonesia. adam_apt@ugm.ac.id.

Daru : Journal of Faculty of Pharmacy, Tehran University of Medical Sciences
|October 24, 2020
PubMed
Abstract

Insights

Atenolol may be repurposed for pancreatic cancer treatment by targeting MMP9 and NF-κB signaling pathways. Further validation is needed for this novel drug discovery approach.

Area of Science:

  • Bioinformatics
  • Network Analysis
  • Drug Discovery

Background:

  • Pancreatic cancer has a low survival rate, necessitating new drug development.
  • Functional network analysis aids in identifying drug candidates through gene, target, and disease interactions.

Purpose of the Study:

  • To investigate the potential repurposing of atenolol, a selective adrenergic inhibitor, for pancreatic cancer treatment.
  • Utilize functional network analysis to identify atenolol's therapeutic targets in pancreatic cancer.

Main Methods:

  • Collected atenolol-mediated proteins (AMPs) from STITCH and STRING databases.
  • Performed gene ontology, KEGG pathway enrichment, genetic alteration, survival, and molecular docking analyses on AMPs.

Main Results:

  • Identified 176 AMPs, including key players in pancreatic cancer pathways like MAPK1, RELA, MAPK8, STAT1, and STAT3.
  • Found significant correlations between high mRNA levels of MAPK1, RELA, STAT3, GNB1, and MMP9 and worse overall survival.
  • Molecular docking identified RELA and MMP9 as potential atenolol targets.

Conclusions:

  • Atenolol shows potential for repurposing against pancreatic cancer by modulating MMP9 and NF-κB signaling.
  • Results suggest atenolol as a candidate for pancreatic cancer therapy, requiring further in vitro and in vivo validation.
Keywords:
AtenololDrug repurposingFunctional networkPancreatic cancer

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