Advances in targeting the Hedgehog signaling pathway in cancer therapy

The Hedgehog (Hh) pathway is one of the central developmental signaling mechanisms, which have recently been shown to contribute to malignant progression of a variety of human cancers. Additionally, the role of Hh and other embryonic signaling pathways in the regulation and maintenance of the tumorigenic cancer stem / -initiating subpopulation underlines the importance of this pathway in human malignancies. The review 'Targeting the Hedgehog signaling pathway for cancer therapy' by Li and coworkers has comprehensively described the potential of pharmacological targeting of Hh signaling. Here we provide an update on the current knowledge on i) the role of this pathway in human tumorigenesis and the rationale for therapeutic targeting, ii) the pharmacological approaches currently being investigated in preclinical and clinical studies, and iii) the outlook for future developments and efforts for establishing Hh antagonists as a valid approach in cancer treatment. Stratification of the tumor type according to Hh-specific expression patterns and clinicopathological characteristics, as well as investigation of possible tumor cell resistance against Hh antagonists, is the central area for further development.