Sonic Hedgehog signaling in advanced prostate cancer

The Hedgehog family of growth factors activate a highly conserved signaling system for cell-cell communication that regulates cell proliferation and differentiation during development. Abnormal activation of the Hedgehog pathway has been demonstrated in a variety of human tumors, including those of the skin, brain, lung and digestive tract. Hedgehog pathway activity in these tumors is required for cancer cell proliferation and tumor growth. Recent studies have uncovered the role for Hedgehog signaling in advanced prostate cancer and demonstrated that autocrine signaling by tumor cells is required for proliferation, viability, and invasive behavior. The level of Hedgehog activity correlates with the severity of the tumor and is both necessary and sufficient for metastatic behavior. Blockade of Hedgehog signaling leads to tumor shrinkage and remission in preclinical tumor xenograft models. Thus, Hedgehog signaling represents a novel pathway in prostate cancer that offers opportunities for prognostic biomarker development, drug targeting and therapeutic response monitoring. Received 18 August 2005; received after revision 30 September 2005; accepted 1 November 2005