Network centric identification of PI3K/Akt hub proteins as key oncogenic drivers and therapeutic targets

Emad Fadhal1

  • 1Department of Mathematics & Statistics, College of Science, King Faisal University, P. O. Box 400, Al-Ahsa, 31982, Saudi Arabia. efadhal@kfu.edu.sa.

Scientific Reports
|November 19, 2025
PubMed

Insights

This study identifies key signaling proteins in the PI3K/Akt pathway using network analysis. Findings suggest co-targeting strategies to overcome cancer therapy resistance and inform precision oncology drug design.

Area of Science:

  • Oncology
  • Systems Biology
  • Bioinformatics

Background:

  • The PI3K/Akt pathway is crucial for cancer cell proliferation, survival, and metabolism.
  • Pathway dysregulation, driven by mutations in genes like PIK3CA and AKT1, promotes tumorigenesis and therapy resistance.

Purpose of the Study:

  • To systematically identify key hub proteins within the human PI3K/Akt protein-protein interaction network.
  • To explore potential co-targeting strategies for overcoming cancer therapy resistance.

Main Methods:

  • Network metric space approach applied to the human protein-protein interaction network.
  • Systematic analysis to identify key hub proteins within the PI3K/Akt pathway.
  • Functional enrichment analysis and oncogene identification.

Main Results:

  • Signaling proteins constitute 100% of identified PI3K/Akt pathway hubs.
  • Significant overlaps were found with MAPK cascades (29.1%) and essential oncogenic drivers (70.8%).
  • 5.8% of identified proteins are classified as oncogenes, highlighting therapeutic relevance.

Conclusions:

  • A systematic, network-based framework for identifying and prioritizing PI3K/Akt pathway hub proteins.
  • Potential for rational multi-target drug design in precision oncology to combat therapy resistance.

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