Itraconazole and Arsenic Trioxide Inhibit Hedgehog Pathway Activation and Tumor Growth Associated with Acquired Resistance to Smoothened Antagonists
作者： James Kim , Blake T. Aftab , Jean Y. Tang , Daniel Kim , Alex H. Lee
DOI: 10.1016/J.CCR.2012.11.017
关键词:
摘要: Recognition of the multiple roles Hedgehog signaling in cancer has prompted intensive efforts to develop targeted pathway inhibitors. Leading inhibitors clinical development act by binding a common site within Smoothened, critical component. Acquired Smoothened mutations, including SMO(D477G), confer resistance these Here, we report that itraconazole and arsenic trioxide, two agents use inhibit mechanisms distinct from current antagonists, retain inhibitory activity vitro context all reported resistance-conferring mutants GLI2 overexpression. Itraconazole alone or combination, growth medulloblastoma basal cell carcinoma vivo, prolong survival mice with intracranial drug-resistant SMO(D477G) medulloblastoma.
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utsystem.edu参考文章(77)
Jingwu Xie, Maximilien Murone, Shiuh-Ming Luoh, Anne Ryan, Qimin Gu, Chaohui Zhang, Jeannette M. Bonifas, Ching-Wan Lam, Mary Hynes, Audrey Goddard, Arnon Rosenthal, Ervin H Epstein, Frederic J. de Sauvage, Activating Smoothened mutations in sporadic basal-cell carcinoma. Nature. ,vol. 391, pp. 90- 92 ,(1998) , 10.1038/34201
Qi Zhu, Ji-Wang Zhang, Hai-Qing Zhu, Yu-Lei Shen, Maria Flexor, Pei-Ming Jia, Yun Yu, Xun Cai, Samuel Waxman, Michel Lanotte, Sai-Juan Chen, Zhu Chen, Jian-Hua Tong, Synergic effects of arsenic trioxide and cAMP during acute promyelocytic leukemia cell maturation subtends a novel signaling cross-talk Blood. ,vol. 99, pp. 1014- 1022 ,(2002) , 10.1182/BLOOD.V99.3.1014
Guido Reifenberger, Marietta Wolter, Julia Reifenberger, Mosaad Megahed, Peter Lichter, Ruthild G. Weber, Thomas Ruzicka, Missense Mutations in SMOH in Sporadic Basal Cell Carcinomas of the Skin and Primitive Neuroectodermal Tumors of the Central Nervous System Cancer Research. ,vol. 58, pp. 1798- 1803 ,(1998)
R. L. Yauch, G. J. P. Dijkgraaf, B. Alicke, T. Januario, C. P. Ahn, T. Holcomb, K. Pujara, J. Stinson, C. A. Callahan, T. Tang, J. F. Bazan, Z. Kan, S. Seshagiri, C. L. Hann, S. E. Gould, J. A. Low, C. M. Rudin, F. J. de Sauvage, Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma Science. ,vol. 326, pp. 572- 574 ,(2009) , 10.1126/SCIENCE.1179386
Richard F. Keeler, Teratogenic compounds of Veratrum californicum (Durand). 13. Structure of muldamine. Steroids. ,vol. 18, pp. 741- 752 ,(1971) , 10.1016/0039-128X(71)90033-X
M VESSEY, Mortality in oral contraceptive users. The Lancet. ,vol. 1, pp. 549- 550 ,(1981) , 10.1016/S0140-6736(81)92875-0
Jeffrey P. Lamb, Darren W. Engers, Colleen M. Niswender, Alice L. Rodriguez, Daryl F. Venable, P. Jeffrey Conn, Craig W. Lindsley, Discovery of molecular switches within the ADX-47273 mGlu5 PAM scaffold that modulate modes of pharmacology to afford potent mGlu5 NAMs, PAMs and partial antagonists Bioorganic & Medicinal Chemistry Letters. ,vol. 21, pp. 2711- 2714 ,(2011) , 10.1016/J.BMCL.2010.11.119
Mae R. Gailani, Mona Ståhle-Bäckdahl, David J. Leffell, Michael Glyn, Peter G. Zaphiropoulos, Anne Birgitte Undén, Michael Dean, Douglas E. Brash, Allen E. Bale, Rune Toftgård, The role of the human homologue of Drosophila patched in sporadic basal cell carcinomas. Nature Genetics. ,vol. 14, pp. 78- 81 ,(1996) , 10.1038/NG0996-78
Hugues de Thé, Christine Chomienne, Michel Lanotte, Laurent Degos, Anne Dejean, The t(15;17) translocation of acute promyelocytic leukaemia fuses the retinoic acid receptor α gene to a novel transcribed locus Nature. ,vol. 347, pp. 558- 561 ,(1990) , 10.1038/347558A0
Lisa V. Goodrich, Ljiljana Milenković, Kay M. Higgins, Matthew P. Scott, Altered Neural Cell Fates and Medulloblastoma in MousepatchedMutants Science. ,vol. 277, pp. 1109- 1113 ,(1997) , 10.1126/SCIENCE.277.5329.1109