Shedding light on complexity of protein–protein interactions in cancer

Most cell signaling and surveillance circuits are physically maintained through a dense network of protein–protein interactions (PPIs). Genetic mutations, epigenetic changes as well as alterations in cellular microenvironment can markedly rewire the patterns of PPIs, which leads to neoplastic growth of cancer cells. There are accumulating evidences that drugs that target-specific PPI pairs may provide an opportunity to treat cancers with a higher specificity and efficacy than those inhibiting enzymatic activity of oncogenic proteins. Therefore, identification of driving PPIs in a given cancer not only improves our understanding for individual cancers, but it also provides therapeutic opportunities to cure the specific cancer. In this review, we introduce some examples of aberrant PPI complexes identified in several major types of cancers, and recent technical developments that permit assessment of PPI strength in clinical specimens. Finally, we discuss the potential use of such PPI profiling for the purpose of precision medicine.