Abstract
Activation of Hedgehog (Hh) signaling is implicated in the development and progression of several tumor types, including prostate cancer, which is still the most common non-skin malignancy and the third leading cause of cancer-related mortality in men in industrialized countries worldwide. Several studies have indicated that the Hh pathway plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states. Moreover, preclinical data have shown that inhibition of Hh signaling has the potential to reduce prostate cancer invasiveness and metastatic potential. Clinical trials investigating the benefit of Hh inhibitors in patients with prostate cancer have recently been initiated. However, acquired drug resistance has already been observed in other tumor types after long-term Hh inhibition. Therefore, combining Hh inhibitors with ionizing radiation, chemotherapy or other molecular targeted agents could represent an alternative therapeutic strategy. In this review, we will highlight the role of Hh signaling in the development and progression of prostate cancer and summarize the different therapeutic applications of Hedgehog inhibition.
Highlights
The Hedgehog (Hh) signaling pathway is essential for numerous processes during embryonic development including cell growth, cell differentiation, patterning and organogenesis
Combined targeting of EGFR and Hh signaling by gefitinib and cyclopamine cooperatively improves the cytotoxic effects of docetaxel on metastatic prostate cancer (PCa) cells [151]
The role of Hh signaling in PCa has actively been investigated and has shown to be involved in the development of PCa and progression to more advanced and castration-resistant disease
Summary
The Hedgehog (Hh) signaling pathway is essential for numerous processes during embryonic development including cell growth, cell differentiation, patterning and organogenesis. In various types of cancer on the other hand, uncontrolled activation of the Hh signaling pathway has been observed [2,5,6,7]. As for prostate cancer (PCa), there is emerging evidence that Hh signaling plays a crucial role in the development as well as in the progression of this disease to more aggressive and even therapy-resistant disease states [1]. We will highlight the role of Hh signaling in the development and progression of PCa and summarize the different therapeutic applications of Hh inhibition
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