Mapping protein interaction networks to uncover new cancer targets

A trio of papers from the Cancer Cell Map Initiative demonstrates how protein interaction networks can identify previously unknown oncogenic drivers. Two studies use affinity purification-mass spectrometry to characterize protein interaction networks in head and neck and breast cancers, while the third combines new data from the two studies with data from 127 prior studies to generate a structured map of protein pathways. Together, the three papers provide a framework that could help identify new therapeutic targets and predictors of response.

Among other findings, the team showed mutant-specific interactions between PIK3CA and HER3 determines response to HER3 inhibitors in head and neck squamous cell carcinoma, and identified UBE2N as a biomarker of response to PARP inhibitors and other DNA repair-targeted therapies in breast cancer. Using the structured protein pathway map, called NeST, the team implicated a total of 548 genes in cancer evolution and progression across 13 tumor types, including 447 genes whose mutations have not previously been associated with cancer...