Identification of anaplastic lymphoma kinase as a potential therapeutic target in Basal Cell Carcinoma.

摘要: // Hanna Ning 1,* , Hiroshi Mitsui Claire Q.F. Wang 1 Mayte Suarez-Farinas 1,2 Juana Gonzalez Kejal R. Shah 3 Jie Chen 4 Israel Coats Diane Felsen John A. Carucci 5 and James G. Krueger Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 2 Center Clinical Translational Science, USA Texas Dermatology Associates, Baylor University Medical Center, Dallas, TX Institute Pediatric Urology, Department of Weill Cornell College, Ronald O. Perelman York Langone * These two authors contributed equally to this manuscript. Correspondence: Krueger, email: Keywords : Basal cell carcinoma, oncogenic kinases, cancer, therapy Received September 1, 2013 Accepted 30, Published October 2, Abstract pathogenesis BCC is associated with sonic hedgehog (SHH) signaling. Vismodegib, a smoothened inhibitor that targets pathway, now in clinical use advanced patients, but its efficacy limited. Therefore, new therapeutic options cancer are required. We studied gene expression profiling tumour tissues coupled laser capture microdissection identify specific receptor tyrosine kinase can be targeted by small molecule inhibitors. found >250 fold increase (FDR<10 -4 ) the oncogene, anaplastic lymphoma (ALK) as well ligands, pleiotrophin midkine compared microdissected normal epidermis. qRT-PCR confirmed increased ALK ( p <0.05). Stronger phosphorylated nests than skin was observed immunohistochemistry. Crizotinib, an FDA-approved inhibitor, reduced keratinocyte proliferation culture, whereas c-Met did not. Crizotinib significantly GLI1 CCND2 (members SHH-pathway) mRNA approximately 60% 20%, respectively <0.01). Our data suggest may parallel conventional SHH-pathway promote proliferation. Hence, alone or combination targeting molecules potential treatment patients.