PTEN loss mitigates the response of medulloblastoma to hedgehog pathway inhibition

Cancer Research

Volumn 73, Issue 23, 2013, Pages 7034-7042

  Metcalfe, Ciara ^a   Alicke, Bruno ^a   Crow, Ailey ^a   Lamoureux, Marlea ^a   Dijkgraaf, Gerrit J P ^a   Peale, Franklin ^a   Gould, Stephen E ^a   De Sauvage, Frederic J ^a  

^a GENENTECH INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SMOOTHENED PROTEIN; SONIC HEDGEHOG PROTEIN; VISMODEGIB;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CANCER RESISTANCE; DOSE RESPONSE; DRUG PROTEIN BINDING; ENZYME INHIBITION; MEDULLOBLASTOMA; MOUSE; MOUSE MODEL; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; TREATMENT RESPONSE; TUMOR MODEL; TUMOR REGRESSION; TUMOR XENOGRAFT; WILD TYPE;

EID: 84890288884     PISSN: 00085472     EISSN: 15387445     Source Type: Journal    
DOI: 10.1158/0008-5472.CAN-13-1222     Document Type: Article

References (34)

1. Polkinghorn WR, Tarbell NJ. Medulloblastoma: tumorigenesis, current clinical paradigm, and efforts to improve risk stratification. Nat Clin Pract Oncol 2007;4:295-304.
2. Taylor MD, Northcott PA, Korshunov A, Remke M, Cho YJ, Clifford SC, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 2012;123:465-72.
3. Northcott PA, Korshunov A, Pfister SM, Taylor MD. The clinical implications of medulloblastoma subgroups. Nat Rev Neurol 2012;8:340-51.
4. Varjosalo M, Taipale J. Hedgehog: functions and mechanisms. Genes Dev 2008;22:2454-72.
5. Epstein EH. Basal cell carcinomas: attack of the hedgehog. Nat Rev Cancer 2008;8:743-54.
6. Pietsch T, Waha A, Koch A, Kraus J, Albrecht S, Tonn J, et al. Medulloblastomas of the desmoplastic variant carry mutations of the human homologue of Drosophila patched. Cancer Res 1997;57:2085-8.
7. Raffel C, Jenkins RB, Frederick L, Hebrink D, Alderete B, Fults DW, et al. Sporadic medulloblastomas contain PTCH mutations. Cancer Res 1997;57:842-5.
8. Wolter M, Reifenberger J, Sommer C, Ruzicka T, Reifenberger G. Mutations in the human homologue of the Drosophila segment polarity gene patched (PTCH) in sporadic basal cell carcinomas of the skin and primitive neuroectodermal tumors of the central nervous system. Cancer Res 1997;57:2581-5.
9. Rudin CM, Hann CL, Laterra J, Yauch RL, Callahan CA, Fu L, et al. Treatment of medulloblastoma with hedgehog pathway inhibitor GDC-0449. N Engl J Med 2009;361:1173-8.
10. Engelman JA, Janne PA. Mechanisms of acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors in non-small cell lung cancer. Clin Cancer Res 2008;14:2895-9.
11. Yauch RL, Dijkgraaf GJ, Alicke B, Januario T, Ahn CP, Holcomb T, et al. Smoothened mutation confers resistance to a Hedgehog pathway inhibitor in medulloblastoma. Science 2009;326:572-4.
12. Pan S, Wu X, Jiang J, Gao WQ, Wan Y, Cheng D, et al. Discovery of NVP-LDE225, a potent and selective smoothened antagonist. ACS Med Chem Lett 2010;1:130-4.
13. Buonamici S, Williams J, Morrissey M, Wang A, Guo R, Vattay A, et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med 2010;2:51ra70.
14. Dijkgraaf GJ, Alicke B, Weinmann L, Januario T, West K, Modrusan Z, et al. Small molecule inhibition of GDC-0449 refractory smoothened mutants and downstreammechanisms of drug resistance. Cancer Res 2010;71:435-44.
15. Song MS, Salmena L, Pandolfi PP. The functions and regulation of the PTEN tumour suppressor. Nat Rev Mol Cell Biol 2012;13:283-96.
16. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, et al. Novel mutations target distinct subgroups ofmedulloblastoma. Nature 2012;488:43-8.
17. Parsons DW, Li M, Zhang X, Jones S, Leary RJ, Lin JC, et al. The genetic landscape of the childhood cancer medulloblastoma. Science 2011;331:435-9.
18. Hartmann W, Digon-Sontgerath B, Koch A,Waha A, Endl E, Dani I, et al. Phosphatidylinositol 3′-kinase/AKT signaling is activated in medulloblastoma cell proliferation and is associated with reduced expression of PTEN. Clin Cancer Res 2006;12:3019-27.
19. Kasper M, Jaks V, Are A, Bergstrom A, Schwager A, Svard J, et al. Wounding enhances epidermal tumorigenesis by recruiting hair follicle keratinocytes. Proc Natl Acad Sci U S A 2011;108:4099-104.
20. Pinheiro JC, Bates DM. Mixed-effects models in S and S-PLUS. New York: Springer; 2000.
21. Yang ZJ, Ellis T, Markant SL, Read TA, Kessler JD, Bourboulas M, et al. Medulloblastoma can be initiated by deletion of Patched in lineage-restricted progenitors or stem cells. Cancer Cell 2008;14:135-45.
22. Ellis T, Smyth I, Riley E, Graham S, Elliot K, Narang M, et al. Patched 1 conditional null allele in mice. Genesis 2003;36:158-61.
23. Wong H, Alicke B, West KA, Pachero P, La H, Januario T, et al. Pharmacokinetic-pharmacodynamic analysis of vismodegib in preclinical models of mutational and ligand-dependent Hedgehog pathway activation. Clin Cancer Res 2011;17:4682-92.
24. Salphati L, Heffron TP, Alicke B, Nishimura M, Barck K, Carano RA, et al. Targeting the PI3K pathway in the brain-efficacy of a PI3K inhibitor optimized to cross the blood-brain barrier. Clin Cancer Res 2012;18:6239-48.
25. Kwon CH, Zhu X, Zhang J, Knoop LL, Tharp R, Smeyne RJ, et al. Pten regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat Genet 2001;29:404-11.
26. Backman SA, Stambolic V, Suzuki A, Haight J, Elia A, Pretorius J, et al. Deletion of Pten in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat Genet 2001;29:396-403.
27. Zhu G, Chow LM, Bayazitov IT, Tong Y, Gilbertson RJ, Zakharenko SS, et al. Pten deletion causes mTorc1-dependent ectopic neuroblast differentiation without causing uniform migration defects. Development 2012;139:3422-31.
28. Hambardzumyan D, Becher OJ, Rosenblum MK, Pandolfi PP, Manova-Todorova K, Holland EC. PI3K pathway regulates survival of cancer stem cells residing in the perivascular niche following radiation in medulloblastoma in vivo. Genes Dev 2008;22:436-48.
29. Castellino RC, Barwick BG, Schniederjan M, Buss MC, Becher O, Hambardzumyan D, et al. Heterozygosity for Pten promotes tumorigenesis in a mouse model of medulloblastoma. PLoS One 2010;5:e10849.
30. Garcia I, Crowther AJ, Gama V, Ryan Miller C, Deshmukh M, Gershon TR. Bax deficiency prolongs cerebellar neurogenesis, accelerates medulloblastoma formation and paradoxically increases both malignancy and differentiation. Oncogene 2012;32:2304-14.
31. Li Y, Maitah MY, Ahmad A, Kong D, Bao B, Sarkar FH. Targeting the Hedgehog signaling pathway for cancer therapy. Expert Opin Ther Targets 2012;16:49-66.
32. Lin TL, Matsui W. Hedgehog pathway as a drug target: smoothened inhibitors in development. Onco Targets Ther 2012;5:47-58.
33. Ng JM, Curran T. The Hedgehog's tale: developing strategies for targeting cancer. Nat Rev Cancer 2011;11:493-501.
34. Lind D, Franken S, Kappler J, Jankowski J, Schilling K. Characterization of the neuronal marker NeuN as a multiply phosphorylated antigen with discrete subcellular localization. J Neurosci Res 2005;79:295-302.