Hedgehog signaling pathway as a therapeutic target in breast cancer

The Hedgehog (Hh) signaling pathway, which is well conserved even in mammals and other vertebrate species, has long been known to direct growth and patterning during embryonic development. It has been shown that the Hh pathway also plays a critical role in mouse normal mammary gland development. Namely, it has been shown that disruption of the Hh pathway-related genes such as Patched-1 and Gli2 leads to ductal dysplasias that closely resemble some hyperplasia of human breast. In addition, it has been reported that breast carcinoma cells have disruption of these genes. These findings strongly indicate a contribution of the Hh pathway to development of human breast carcinoma. In fact, constitutive activation of the Hh pathway was found in most of 52 surgically resected breast carcinoma specimens. Interestingly, exposure to cyclopamine, a steroidal alkaroid that blocks the Hh pathway, suppressed the growth of the Hh pathway-activated breast carcinoma cells. Thus, the Hh pathway may function in progression of breast carcinoma. In this short review, possibilities of the Hh pathway as a new therapeutic target in breast carcinoma will be mainly discussed. (C) 2004 Elsevier Ireland Ltd. All rights reserved.