CURIS, INC.;GENENTECH, INC.;ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS;UNIVERSITE PARIS DIDEROT - PARIS 7; INC.;GENENTECH
发明人:
DE SAUVAGE, FREDERIC J.,YAUCH, ROBERT L.,DIJKGRAAF, GERRIT J.P.,SHARPE, HAYLEY,BASSET-SEGUIN, NICOLE
申请号：
CA2975875
公开号：
CA2975875A1
申请日:
2016.02.04
申请国别(地区):
CA
年份:
2016
代理人:
摘要：
The emergence of mutations in tyrosine kinases following treatment of cancer patients with molecular-targeted therapy represents a major mechanism, of acquired drug resistance. Here, mutations in the serpentine receptor, Smoothened (SMO) are described, which result in resistance to a Hedgehog (Hh) pathway inhibitor, such as in medulloblastoma. Amino acid substitutions in conserved residues of SMO maintain Hh signaling, but result in the inability of the Hh pathway inhibitor, GDC-0449, to bind SMO and suppress the pathway. In some embodiments, the disclosure provides for novel mutant SMO proteins and nucleic acids and for screening metliods to detect SMO mutations and methods to screen for drugs that specifically modulate mutant SMO exhibiting drug resistance.
