The crystal structure of vismodegib has been solved and refined using synchrotron X-ray powder diffraction data, optimized density functional theory techniques. Vismodegib crystallizes in space group P2 1 / a (#14) with = 16.92070(20), b 10.20235(4), c 12.16161(10) Å, β 108.6802(3)°, V 1988.873(9) Å 3 , Z 4. consists corrugated layers molecules parallel to the bc -plane. There is only one class...

Abstract We report the case of a 50-year-old woman, with history Gorlin syndrome on vismodegib therapy, who presented two episodes upper gastrointestinal bleeding (UGIB) in absence other risk factors. is rare disorder characterized by multiple basal cell carcinomas (BCCs) secondary to mutation PTCH1. Mutations PTCH1 lead dysregulation hedgehog signalling pathway and subsequent abnormal prolifer...

The data and regulatory considerations leading to the U.S. Food and Drug Administration (FDA) January 30, 2012 approval of Erivedge (vismodegib) capsules for the treatment of patients with recurrent, locally advanced, or metastatic basal cell carcinoma (BCC) are described. The FDA's approval decision was based primarily on the results observed in a single-arm, parallel cohort, international tri...

Background Response to targeting and non-targeting agents is variable and molecular information remains poorly described in patients with recurrent sonic-hedgehog-driven medulloblastoma (SHH-MB). Materials and Methods Clinical and PET/CT findings during treatment with successive hedgehog antagonists and temozolomide monotherapies are described in a heavily pre-treated patient with recurrent e...

cells that have a compensatory amplification of genes downstream from SMO such as Gli. In individuals with multiple resistant BCCs, the isogenic background of a single individual may facilitate molecular studies of these resistant BCCs because some of the tumors may become resistant through multiple mechanisms. Future efforts to attack or prevent resistance in BCCs may involve the use of more t...

PURPOSE To assess the tumor response to the smoothened (SMO) inhibitor, sonidegib (LDE225), in patients with an advanced basal cell carcinoma (BCC) resistant to treatment with vismodegib (GDC0449). EXPERIMENTAL DESIGN Nine patients with an advanced BCC that was previously resistant to treatment with vismodegib were given sonidegib in this investigational, open-label study. Tumor response was ...

IMPORTANCE Basal cell carcinoma (BCC) represents 90% of malignant eyelid tumors and is locally invasive and destructive, if left untreated. OBJECTIVE To assess the feasibility of using vismodegib for periocular and orbital BCC based on its efficacy and tolerability. DESIGN, SETTING, AND PARTICIPANTS In this prospective observational case series, consecutive patients with periocular or orbit...

Basal cell carcinoma (BCC) accounts for 80% of all non-melanoma skin cancer [1]. Advanced disease is infrequently seen, but when present can be a surgical challenge or even life threatening. Recent studies show that mutations in the hedgehog (HH) signaling pathway are associated with the majority of BCC. Hedgehog protein binds to patched homologue 1 (PTCH1) transmembrane receptor, which prevent...

Abstract Medulloblastoma is the most common malignant pediatric brain tumor. Despite fair efficacy of current treatment approaches, 30 % patients with medulloblastoma relapse. Cells expressing stemness biomarker SRY (sex determining region Y)-box 2 (SOX2) are known to play key roles in sustaining growth, providing chemo-resistance, and driving tumor It therefore critical elucidate underlying me...