Novel modeling of cancer cell signaling pathways enables systematic drug repositioning for distinct breast cancer metastases.

ABSTRACT: A new type of signaling network element, called cancer signaling bridges (CSB), has been shown to have the potential for systematic and fast-tracked drug repositioning. On the basis of CSBs, we developed a computational model to derive specific downstream signaling pathways that reveal previously unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available patient gene expression data. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed specific CSBs for each metastasis that satisfy (i) CSB proteins are activated by the maximal

SUBMITTER: Zhao H 

PROVIDER: S-EPMC4005386 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature