Clinical experience with Hedgehog pathway inhibitors - PubMed (original) (raw)

. 2010 Dec 20;28(36):5321-6.

doi: 10.1200/JCO.2010.27.9943. Epub 2010 Nov 1.

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Clinical experience with Hedgehog pathway inhibitors

Jennifer A Low et al. J Clin Oncol. 2010.

Abstract

The Hedgehog (Hh) signaling pathway is critical for cell growth and differentiation during embryogenesis and early development. While it is mostly quiescent in adults, inappropriate reactivation of the Hh pathway has been shown to be involved in the development of cancer. A number of tumor types rely on overexpression of Hh ligands to activate the pathway in a paracrine manner from the tumor to the surrounding stroma. Alternatively, Hh ligands may act on cancer stem cells in some hematopoietic cancers, such as chronic myelogenous leukemia. However, the role of the Hh pathway is best established in tumors, such as basal cell carcinoma and medulloblastoma, where the pathway is activated via mutations. Understanding the contribution of Hh signaling in these various tumor types will be critical to the development and use of agents targeting this pathway in the clinic. We review here the activity of clinical inhibitors of the Hh pathway, including GDC-0449, a small molecule inhibitor of Smoothened (SMO).

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