Pharmacologically controlling protein-protein interactions through epichaperomes for therapeutic vulnerability in cancer.

ABSTRACT: Cancer cell plasticity due to the dynamic architecture of interactome networks provides a vexing outlet for therapy evasion. Here, through chemical biology approaches for systems level exploration of protein connectivity changes applied to pancreatic cancer cell lines, patient biospecimens, and cell- and patient-derived xenografts in mice, we demonstrate interactomes can be re-engineered for vulnerability. By manipulating epichaperomes pharmacologically, we control and anticipate how thousands of proteins interact in real-time within tumours. Further, we can essentially force tumours into interactome hyperconnectivity and maximal protein-protein interaction capacity, a state whereby no rebound pathways can be deployed and where alternative signalling is supressed. This approach therefore p

SUBMITTER: Joshi S 

PROVIDER: S-EPMC8617294 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature