Smoothened mutation confers resistance to a hedgehog pathway inhibitor in medulloblastoma

Science

Volumn 326, Issue 5952, 2009, Pages 572-574

  Yauch, Robert L ^a   Dijkgraaf, Gerrit J P ^a   Alicke, Bruno ^a   Januário, Thomas ^a   Ahn, Christina P ^a   Holcomb, Thomas ^a   Pujara, Kanan ^a   Stinson, Jeremy ^a   Callahan, Christopher A ^a   Tang, Tracy ^a   Bazan, J Fernando ^a   Kan, Zhengyan ^a   Seshagiri, Somasekar ^a   Hann, Christine L ^b   Gould, Stephen E ^a   Low, Jennifer A ^a   Rudin, Charles M ^a   De Sauvage, Frederic J ^a  

^a GENENTECH INC   (United States)

^b JOHNS HOPKINS UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; ASPARTIC ACID; G PROTEIN COUPLED RECEPTOR; GDC 0449; PROTEIN INHIBITOR; PROTEIN PATCHED 1; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; UNCLASSIFIED DRUG;

AMINO ACID; CANCER; CHEMICAL BONDING; DISEASE TREATMENT; DRUG RESISTANCE; GENE EXPRESSION; MUTATION; NEUROLOGY; PROTEIN;

ALLELE; AMINO ACID SUBSTITUTION; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; CANCER GROWTH; CANCER RELAPSE; CANCER RESISTANCE; CONTROLLED STUDY; DRUG MECHANISM; DRUG TARGETING; GENE MUTATION; GENOTYPE; HETEROZYGOSITY LOSS; HUMAN; HUMAN TISSUE; MEDULLOBLASTOMA; MOUSE; MUTATIONAL ANALYSIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN TARGETING; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANILIDES; ANIMALS; ANTINEOPLASTIC AGENTS; BRAIN NEOPLASMS; CELL LINE, TUMOR; CINNAMATES; DRUG RESISTANCE, NEOPLASM; HEDGEHOG PROTEINS; HUMANS; MEDULLOBLASTOMA; MICE; MOLECULAR SEQUENCE DATA; MUTANT PROTEINS; MUTATION, MISSENSE; NEOPLASM METASTASIS; PROTEIN CONFORMATION; PYRIDINES; RECEPTORS, CELL SURFACE; RECEPTORS, G-PROTEIN-COUPLED; SIGNAL TRANSDUCTION; VERATRUM ALKALOIDS;

ERINACEIDAE;

EID: 70350496540     PISSN: 00368075     EISSN: 10959203     Source Type: Journal    
DOI: 10.1126/science.1179386     Document Type: Article

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19. We thank L Fu, H. Tian, Z. Zhang, K. Toy, Z. Modrusan, L Li, S. Scales, and T. Wu for their contributions to this manuscript. Patient-informed consent was obtained for the research performed in this study. C.M.R. received research funding from Genentech for a GDC-0449 phase I trial and received a BioOncology Grant Program Award from Genentech. All authors, except C.M.R. and C.L.H., are employees of Genentech. F.J.S. holds patents related to hedgehog signaling.