HEDGEHOG SIGNALING The Hedgehog(19) signaling pathway is important for normal mammalian embryonic development and for adult tissue remodeling. Recent reports have demonstrated that aberrant activation of the Hh pathway is associated with many types of cancer, including basal cell carcinoma (BCC), medulloblastoma, pancreatic adenocarcinomas, small-cell lung cancer (SCLC), metastatic prostate cancer, glioma, breast cancer, hepatocellular cancer, and hematologic malignancies. High levels of Hh pathway activation, either through mutation of pathway components or through constitutive expression of Hh pathway genes, appear to be involved in both the initiation of cancer and tumor cell survival, as well as tumor growth and metastasis. Given the therapeutic potential of Hh pathway inhibition in cancer, Infinity has developed IPI-926, a potent and specific antagonist of the Hh pathway that binds Smoothened (Smo), a key signaling transmembrane protein in this pathway, thereby diminishing downstream promoters of cellular proliferation.