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

The PI3K/Akt pathway plays a central role in cancer progression by regulating cell proliferation, survival, and metabolism. Dysregulation of this pathway, often due to mutations in genes such as PIK3CA, PTPN11, EGFR, and AKT1, contributes to tumorigenesis and therapy resistance. Using a network metric space approach, we systematically analyzed the human protein-protein interaction network to identify key hub proteins. Our findings suggest that signaling proteins dominate the PI3K/Akt pathway (100%), with significant overlaps in MAPK cascades (29.1%) and essential oncogenic drivers (70.8%), indicating potential co-targeting strategies to overcome resistance. Functional enrichment analysis highlights the therapeutic relevance of these hubs, while 5.8% of identified proteins are oncogenes, reinforcing their candidacy for therapies. This study provides a systematic, network-based framework for identifying and prioritizing hub proteins in the PI3K/Akt pathway, with potential implications for rational multi-target drug design in precision oncology.