Systemic network analysis identifies XIAP and IκBα as potential drug targets in TRAIL resistant BRAF mutated melanoma.

ABSTRACT: Metastatic melanoma remains a life-threatening disease because most tumors develop resistance to targeted kinase inhibitors thereby regaining tumorigenic capacity. We show the 2nd generation hexavalent TRAIL receptor-targeted agonist IZI1551 to induce pronounced apoptotic cell death in mutBRAF melanoma cells. Aiming to identify molecular changes that may confer IZI1551 resistance we combined Dynamic Bayesian Network modelling with a sophisticated regularization strategy resulting in sparse and context-sensitive networks and show the performance of this strategy in the detection of cell line-specific deregulations of a signalling network. Comparing IZI1551-sensitive to IZI1551-resistant melanoma cells the model accurately and correctly predicted activation of NFκB in concert with upr

SUBMITTER: Del Mistro G 

PROVIDER: S-EPMC6218484 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature