发明名称 |
MUTANT SMOOTHENED AND METHODS OF USING THE SAME |
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. |
申请公布号 |
WO2016126972(A1) |
申请公布日期 |
2016.08.11 |
申请号 |
WO2016US16614 |
申请日期 |
2016.02.04 |
申请人 |
GENENTECH, INC.;CURIS, INC.;ASSISTANCE PUBLIQUE-HOPITAUX DE PARIS;UNIVERSITE PARIS DIDEROT - PARIS 7 |
发明人 |
DE SAUVAGE, FREDERIC, J.;YAUCH, ROBERT, L.;DIJKGRAAF, GERRIT, J.P.;SHARPE, HAYLEY;BASSET-SEGUIN, NICOLE |
分类号 |
C07K14/705;C12Q1/68 |
主分类号 |
C07K14/705 |
代理机构 |
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代理人 |
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主权项 |
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地址 |
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