Signaling Inhibitors in the Treatment of Prostate Cancer

Inhibiting androgen receptor (AR) activation through medical or surgicalcastration and blockade of AR-androgen binding is the cornerstone oftreatment for advanced prostate cancer. However, in most cases tumorgrowth eventually becomes androgen independent. Alternative mechanisms ofAR activation, some of which involve growth factor receptor signaling,have been demonstrated in prostate cancer models, and it is likely that anumber of autocrine and paracrine growth factor ligand-receptorinteractions such as those of epidermal growth factors, fibroblast growthfactors, and insulin-like growth factors contribute to the androgenindependent phenotype by promoting cell proliferation and survival.Blocking activation through growth factor receptors and upstream signalingproteins has emerged as a credible approach to cancer treatment.Successful application of this approach in prostate cancer using a growingarray of small molecule kinase inhibitors, antibodies, and antisenseoligonucleotides will be greatly accelerated by elucidation of the keysignaling pathways that maintain the androgen independent phenotype.