Protein-Protein Interactions (PPIs) drive major signalling cascades and play critical role
in cell proliferation, apoptosis, angiogenesis and trafficking. Deregulated PPIs are implicated in multiple
malignancies and represent the critical targets for treating cancer. Herein, we discuss the key
protein-protein interacting domains implicated in cancer notably PDZ, SH2, SH3, LIM, PTB, SAM
and PH. These domains are present in numerous enzymes/kinases, growth factors, transcription factors,
adaptor proteins, receptors and scaffolding proteins and thus represent essential sites for targeting
cancer. This review explores the candidature of various proteins involved in cellular trafficking
(small GTPases, molecular motors, matrix-degrading enzymes, integrin), transcription (p53, cMyc),
signalling (membrane receptor proteins), angiogenesis (VEGFs) and apoptosis (BCL-2family),
which could possibly serve as targets for developing effective anti-cancer regimen. Interactions between
Ras/Raf; X-linked inhibitor of apoptosis protein (XIAP)/second mitochondria-derived activator
of caspases (Smac/DIABLO); Frizzled (FRZ)/Dishevelled (DVL) protein; beta-catenin/T Cell
Factor (TCF) have also been studied as prospective anticancer targets. Efficacy of diverse molecules/
drugs targeting such PPIs although evaluated in various animal models/cell lines, there is an
essential need for human-based clinical trials. Therapeutic strategies like the use of biologicals, high
throughput screening (HTS) and fragment-based technology could play an imperative role in designing
cancer therapeutics. Moreover, bioinformatic/computational strategies based on genome sequence,
protein sequence/structure and domain data could serve as competent tools for predicting
PPIs. Exploring hot spots in proteomic networks represents another approach for developing targetspecific
therapeutics. Overall, this review lays emphasis on a productive amalgamation of proteomics,
genomics, biochemistry, and molecular dynamics for successful treatment of cancer.
