Compensatory pathways induced by MEK inhibition are effective drug targets for combination therapy against castration-resistant prostate cancer.

ABSTRACT: Targeted therapies have often given disappointing results when used as single agents in solid tumors, suggesting the importance of devising rational combinations of targeted drugs. We hypothesized that construction of such combinations could be guided by identification of growth and survival pathways whose activity or expression become upregulated in response to single-agent drug treatment. We mapped alterations in signaling pathways assessed by gene array and protein phosphorylation to identify compensatory signal transduction pathways in prostate cancer xenografts treated with a MAP/ERK kinase (MEK) inhibitor PD325901. In addition to numerous components of the extracellular signal-regulated kinase (ERK) signaling pathway, components of the IKK, hedgehog, and phosphoinositide 3-kinase/Akt

SUBMITTER: Gioeli D 

PROVIDER: S-EPMC3315368 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature