osi-027 and Carcinoma--Basal-Cell

Advanced basal cell carcinomas (BCCs) are driven by the Hedgehog (HH) pathway and often possess inherent resistance to SMO inhibitors. Identifying and targeting pathways that bypass SMO could provide alternative treatments for patients with advanced or metastatic BCC. Here, we use a combination of RNA-sequencing analysis of advanced human BCC tumor-normal pairs and immunostaining of human and mouse BCC samples to identify an MTOR expression signature in BCC. Pharmacological inhibition of MTOR activity in BCC cells significantly reduces cell proliferation without affecting HH signalling. Similarly, treatment of the Ptch1 

Topics: Animals; Antineoplastic Agents; Carcinoma, Basal Cell; Cell Line, Tumor; Cell Proliferation; Everolimus; Hedgehog Proteins; Humans; Imidazoles; Immunohistochemistry; Mice; Patched-1 Receptor; Protein Kinase C; Sequence Analysis, RNA; Signal Transduction; Sirolimus; Skin Neoplasms; TOR Serine-Threonine Kinases; Triazines; Zinc Finger Protein GLI1