The emergence and convergence of cancer genomics,
targeted therapies, and network oncology have significantly
expanded the landscape of protein–protein interaction
(PPI) networks in cancer for therapeutic
discovery. Extensive biological and clinical investigations
have led to the identification of protein interaction
hubs and nodes that are critical for the acquisition and
maintenance of characteristics of cancer essential for
cell transformation. Such cancer-enabling PPIs have
become promising therapeutic targets. With technological
advances in PPI modulator discovery and validation
of PPI-targeting agents in clinical settings, targeting of
PPI interfaces as an anticancer strategy has become a
reality. Future research directed at genomics-based PPI
target discovery, PPI interface characterization, PPIfocused
chemical library design, and patient-genomic
subpopulation-driven clinical studies is expected to accelerate
the development of the next generation of PPIbased
anticancer agents for personalized precision
medicine. Here we briefly review prominent PPIs that
mediate cancer-acquired properties, highlight recognized
challenges and promising clinical results in targeting
PPIs, and outline emerging opportunities.