gdc-0449 and Idiopathic-Pulmonary-Fibrosis

Idiopathic pulmonary fibrosis (IPF) is associated with aberrant expression of developmental pathways, including Hedgehog (Hh). As Hh signalling contributes to multiple pro-fibrotic processes, Hh inhibition may represent a therapeutic option for IPF. However, no non-invasive biomarkers are available to monitor lung Hh activity.. We assessed gene and protein expression in IPF and control lung biopsies, mouse lung, fibroblasts stimulated in vitro with sonic hedgehog (SHh), and plasma in IPF patients versus controls, and cancer patients before and after treatment with vismodegib, a Hh inhibitor.. Lung tissue from IPF patients exhibited significantly greater expression of Hh-related genes versus controls. The gene most significantly upregulated in both IPF lung biopsies and fibroblasts stimulated in vitro with SHh was. CXCL14 is a systemic biomarker that could be used to identify IPF patients with increased Hh pathway activity and monitor the pharmacodynamic effects of Hh antagonist therapy in IPF.. Post-results, NCT00968981.

Topics: Aged; Anilides; Animals; Antineoplastic Agents; Biomarkers; Cells, Cultured; Chemokines, CXC; Female; Gene Expression Regulation; Hedgehog Proteins; Humans; Idiopathic Pulmonary Fibrosis; Lung; Male; Mice, Inbred C57BL; Middle Aged; Neoplasms; Pyridines; Signal Transduction; Up-Regulation