title: Hedgehog Signaling in Malignant Pleural Mesothelioma.
abstract: Malignant pleural mesothelioma (MPM) is a cancer associated with exposure to asbestos fibers, which accumulate in the pleural space, damage tissue and stimulate regeneration. Hedgehog signaling is a pathway important during embryonic mesothelium development and is inactivated in adult mesothelium. The pathway is reactivated in some MPM patients with poor clinical outcome, mainly mediated by the expression of the ligands. Nevertheless, mutations in components of the pathway have been observed in a few cases. Data from different MPM animal models and primary culture suggest that both autocrine and paracrine Hedgehog signaling are important to maintain tumor growth. Drugs inhibiting the pathway at the level of the smoothened receptor (Smo) or glioma-associated protein transcription factors (Gli) have been used mostly in experimental models. For clinical development, biomarkers are necessary for the selection of patients who can benefit from Hedgehog signaling inhibition.
authors.affiliation: University Hospital Zurich, Laboratory of Molecular Oncology, Clinic of Oncology, Haeldeliweg 4, 8044 Zürich, Switzerland. emanuela.felley-bosco@usz.ch.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Felley-Bosco
authors.affiliation: University Hospital Zurich, Division of Thoracic Surgery, Raemistrasse 100, 8091 Zurich, Switzerland. isabelle.schmitt-opitz@usz.ch.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Opitz
authors.affiliation: University Hospital Zurich, Division of Thoracic Surgery, Raemistrasse 100, 8091 Zurich, Switzerland. mayura.meerang@usz.ch.
authors.forename: Mayura
authors.initials: M
authors.lastname: Meerang
keywords: Gli-1; HHip; Hedgehog signaling; TCGA; autocrine signaling; desert Hedgehog; malignant pleural mesothelioma; paracrine signaling