PI-3K inhibitors preferentially target CD15+ cancer stem cell population in SHH driven medulloblastoma

PLoS ONE

Volumn 11, Issue 3, 2016, Pages

  Singh, Alok R ^a   Joshi, Shweta ^a   Zulcic, Muamera ^a   Alcaraz, Michael ^a   Garlich, Joseph R ^b   Morales, Guillermo A ^b   Cho, Yoon J ^c   Bao, Lei ^a   Levy, Michael L ^d   Newbury, Robert ^d   Malicki, Denise ^d   Messer, Karen ^a   Crawford, John ^d   Durden, Donald L ^a,d  

^a UNIVERSITY OF CALIFORNIA SAN DIEGO   (United States)

^b SignalRx Pharmaceuticals   (United States)

^c STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^d RADY CHILDREN'S HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BUPARLISIB; CD15 ANTIGEN; CISPLATIN; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; SONIC HEDGEHOG PROTEIN; SONIDEGIB; TEMOZOLOMIDE; AMINOPYRIDINE DERIVATIVE; ANTINEOPLASTIC AGENT; FUCOSYLTRANSFERASE; FUT4 PROTEIN, MOUSE; MORPHOLINE DERIVATIVE; NADH DEHYDROGENASE SUBUNIT 2, MOUSE; NVP-BKM120; PTEN PROTEIN, MOUSE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE; SHH PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CHEMOTHERAPY; CANCER INHIBITION; CANCER STEM CELL; CELL CYCLE ARREST; CELL POPULATION; CELL PROLIFERATION; CELL SURVIVAL; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG SENSITIVITY; DRUG TARGETING; HUMAN; HUMAN CELL; MEDULLOBLASTOMA; MOUSE; NONHUMAN; PROTEIN FUNCTION; SIGNAL TRANSDUCTION; TRANSGENIC MOUSE; TUMOR XENOGRAFT; ANIMAL; ANTAGONISTS AND INHIBITORS; CANCER TRANSPLANTATION; CEREBELLAR NEOPLASMS; DRUG EFFECTS; DRUG RESISTANCE; DRUG SCREENING; GENE EXPRESSION REGULATION; GENETICS; METABOLISM; MICROARRAY ANALYSIS; MOLECULARLY TARGETED THERAPY; PATHOLOGY; STEREOTACTIC PROCEDURE; TUMOR CELL LINE;

AMINOPYRIDINES; ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CEREBELLAR NEOPLASMS; DRUG RESISTANCE, NEOPLASM; FUCOSYLTRANSFERASES; GENE EXPRESSION REGULATION, NEOPLASTIC; HEDGEHOG PROTEINS; HUMANS; MEDULLOBLASTOMA; MICE; MICE, TRANSGENIC; MICROARRAY ANALYSIS; MOLECULAR TARGETED THERAPY; MORPHOLINES; NADH DEHYDROGENASE; NEOPLASM TRANSPLANTATION; NEOPLASTIC STEM CELLS; PHOSPHATIDYLINOSITOL 3-KINASES; PTEN PHOSPHOHYDROLASE; SIGNAL TRANSDUCTION; STEREOTAXIC TECHNIQUES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84961266647     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0150836     Document Type: Article

References (55)

1. Louis D OH, Wiestler OD, Cavenee WK. WHO Classification of Tumours of the Central Nervous System. International Agency for Research on Cancer (IARC). 2007.; ( 4th ed. Lyon, France).
2. Mehta M CS, Newton H, Guha A, Vogelbaum M. Principles and Practice of Neuro-oncology: A Multidisciplinary Approach. Demos Medical Publishing. 2011. (Oct 21 2010);(( 1st ed) New York, NY).
3. Crawford JR, MacDonald TJ, Packer RJ. Medulloblastoma in childhood: New biological advances. Lancet Neurol. 2007; 6(12):1073-85. Epub 2007/11/23. S1474-4422(07)70289-2 [pii] doi: 10.1016/S1474-4422(07)70289-2 PMID: 18031705.
4. Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, et al. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome. J Clin Oncol. 2011; 29(11):1424-30. Epub 2010/11/26. doi: 10.1200/JCO.2010.28.5148 [pii]. PMID: 21098324; PubMed Central PMCID: PMC3082983.
5. Kool M, Koster J, Bunt J, Hasselt NE, Lakeman A, Van Sluis P, et al. Integrated genomics identifies five medulloblastoma subtypes with distinct genetic profiles, pathway signatures and clinicopathological features. PLoS One. 2008; 3(8):e3088. Epub 2008/09/05. doi: 10.1371/journal.pone.0003088 PMID: 18769486; PubMed Central PMCID: PMC2518524.
6. Northcott PA, Korshunov A, Witt H, Hielscher T, Eberhart CG, Mack S, et al. Medulloblastoma comprises four distinct molecular variants. J Clin Oncol. 2011; 29(11):1408-14. Epub 2010/09/09. JCO.2009.27.4324 [pii] doi: 10.1200/JCO.2009.27.4324 PMID: 20823417.
7. Remke M, Hielscher T, Northcott PA, Witt H, Ryzhova M, Wittmann A, et al. Adult medulloblastoma comprises three major molecular variants. J Clin Oncol. 2011; 29(19):2717-23. Epub 2011/06/03. JCO.2011.34.9373 [pii] doi: 10.1200/JCO.2011.34.9373 PMID: 21632505.
8. Thompson MC, Fuller C, Hogg TL, Dalton J, Finkelstein D, Lau CC, et al. Genomics identifies medulloblastoma subgroups that are enriched for specific genetic alterations. J Clin Oncol. 2006; 24(12):1924-31. Epub 2006/03/29. JCO.2005.04.4974 [pii] doi: 10.1200/JCO.2005.04.4974 PMID: 16567768.
9. Ingham PW, Placzek M. Orchestrating ontogenesis: Variations on a theme by sonic hedgehog. Nat Rev Genet. 2006; 7(11):841-50. Epub 2006/10/19. nrg1969 [pii] doi: 10.1038/nrg1969 PMID: 17047684.
10. Schuller U, Heine VM, Mao J, Kho AT, Dillon AK, Han YG, et al. Acquisition of granule neuron precursor identity is a critical determinant of progenitor cell competence to form Shh-induced medulloblastoma. Cancer Cell. 2008; 14(2):123-34. Epub 2008/08/12. S1535-6108(08)00230-4 [pii] doi: 10.1016/j.ccr. 2008.07.005 PMID: 18691547; PubMed Central PMCID: PMC2597270.
11. Wechsler-Reya R, Scott MP. The developmental biology of brain tumors. Annu Rev Neurosci. 2001; 24:385-428. Epub 2001/04/03. doi: 10.1146/annurev.neuro.24.1.385 [pii]. PMID: 11283316.
12. Tremblay MR, Nesler M, Weatherhead R, Castro AC. Recent patents for Hedgehog pathway inhibitors for the treatment of malignancy. Expert Opin Ther Pat. 2009; 19(8):1039-56. Epub 2009/06/10. doi: 10. 1517/13543770903008551 PMID: 19505195.
13. 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(12):1173-8. Epub 2009/09/04. NEJMoa0902903 [pii] doi: 10.1056/NEJMoa0902903 PMID: 19726761.
14. 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(51):51ra70. Epub 2010/10/01. doi: 10.1126/scitranslmed.3001599 2/51/51ra70 [pii]. PMID: 20881279; PubMed Central PMCID: PMC3422576.
15. 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(5): E10849. Epub 2010/06/04. doi: 10.1371/journal.pone.0010849 PMID: 20520772; PubMed Central PMCID: PMC2877103.
16. 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(10):3019-27. Epub 2006/05/19. 12/10/3019 [pii] doi: 10.1158/1078-0432.CCR-05-2187 PMID: 16707597.
17. Cully M, You H, Levine AJ, Mak TW. Beyond PTEN mutations: The PI3K pathway as an integrator of multiple inputs during tumorigenesis. Nat Rev Cancer. 2006; 6(3):184-92. Epub 2006/02/03. nrc1819 [pii] doi: 10.1038/nrc1819 PMID: 16453012.
18. Huse JT, Holland EC. Targeting brain cancer: Advances in the molecular pathology of malignant glioma and medulloblastoma. Nat Rev Cancer. 2010; 10(5):319-31. Epub 2010/04/24. nrc2818 [pii] doi: 10. 1038/nrc2818 PMID: 20414201.
19. Broderick DK, Di C, Parrett TJ, Samuels YR, Cummins JM, McLendon RE, et al. Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res. 2004; 64(15):5048-50. Epub 2004/08/04. doi: 10.1158/0008-5472.CAN-04-1170 64/15/5048 [pii]. PMID: 15289301.
20. Bigner SH, Mark J, Friedman HS, Biegel JA, Bigner DD. Structural chromosomal abnormalities in human medulloblastoma. Cancer Genet Cytogenet. 1988; 30(1):91-101. Epub 1988/01/01. 0165-4608 (88)90096-9 [pii]. PMID: 3422050.
21. Kool M, Jones DT, Jager N, Northcott PA, Pugh TJ, Hovestadt V, et al. Genome sequencing of SHH medulloblastoma predicts genotype-related response to smoothened inhibition. Cancer Cell. 2014; 25 (3):393-405. Epub 2014/03/22. doi: 10.1016/j.ccr.2014.02.004 S1535-6108(14)00073-7 [pii]. PMID: 24651015; PubMed Central PMCID: PMC4493053.
22. Robinson G, Parker M, Kranenburg TA, Lu C, Chen X, Ding L, et al. Novel mutations target distinct subgroups of medulloblastoma. Nature. 2012; 488(7409):43-8. Epub 2012/06/23. doi: 10.1038/nature11213 [pii]. PMID: 22722829; PubMed Central PMCID: PMC3412905.
23. Read TA, Fogarty MP, Markant SL, McLendon RE, Wei Z, Ellison DW, et al. Identification of CD15 as a marker for tumor-propagating cells in a mouse model of medulloblastoma. Cancer Cell. 2009; 15 (2):135-47. Epub 2009/02/03. doi: 10.1016/j.ccr.2008.12.016 S1535-6108(08)00435-2 [pii]. PMID: 19185848; PubMed Central PMCID: PMC2664097.
24. Ward RJ, Lee L, Graham K, Satkunendran T, Yoshikawa K, Ling E, et al. Multipotent CD15+ cancer stem cells in patched-1-deficient mouse medulloblastoma. Cancer Res. 2009; 69(11):4682-90. Epub 2009/06/03. 69/11/4682 [pii] doi: 10.1158/0008-5472.CAN-09-0342 PMID: 19487286.
25. Capela A, Temple S. LeX is expressed by principle progenitor cells in the embryonic nervous system, is secreted into their environment and binds Wnt-1. Dev Biol. 2006; 291(2):300-13. Epub 2006/02/07. S0012-1606(05)00909-7 [pii] doi: 10.1016/j.ydbio.2005.12.030 PMID: 16458284.
26. Capela A, Temple S. LeX/ssea-1 is expressed by adult mouse CNS stem cells, identifying them as nonependymal. Neuron. 2002; 35(5):865-75. Epub 2002/10/10. S0896627302008358 [pii]. PMID: 12372282.
27. Bao S, Wu Q, McLendon RE, Hao Y, Shi Q, Hjelmeland AB, et al. Glioma stem cells promote radioresistance by preferential activation of the DNA damage response. Nature. 2006; 444(7120):756-60. Epub 2006/10/20. nature05236 [pii] doi: 10.1038/nature05236 PMID: 17051156.
28. Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T, et al. Identification of human brain tumour initiating cells. Nature. 2004; 432(7015):396-401. Epub 2004/11/19. nature03128 [pii] doi: 10.1038/nature03128 PMID: 15549107.
29. Huntly BJ, Gilliland DG. Cancer biology: Summing up cancer stem cells. Nature. 2005; 435 (7046):1169-70. Epub 2005/07/01. 4351169a [pii] doi: 10.1038/4351169a PMID: 15988505.
30. Reya T, Morrison SJ, Clarke MF, Weissman IL. Stem cells, cancer, and cancer stem cells. Nature. 2001; 414(6859):105-11. Epub 2001/11/02. doi: 10.1038/35102167 [pii]. PMID: 11689955.
31. Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007; 104(41):16158-63. Epub 2007/10/04. 0702596104 [pii] doi: 10.1073/pnas.0702596104 PMID: 17911267; PubMed Central PMCID: PMC2042178.
32. Dubrovska A, Kim S, Salamone RJ, Walker JR, Maira SM, Garcia-Echeverria C, et al. The role of PTEN/Akt/PI3K signaling in the maintenance and viability of prostate cancer stem-like cell populations. Proc Natl Acad Sci U S A. 2009; 106(1):268-73. Epub 2009/01/01. doi: 10.1073/pnas.0810956106 [pii]. PMID: 19116269; PubMed Central PMCID: PMC2629188.
33. Yang Y, Iwanaga K, Raso MG, Wislez M, Hanna AE, Wieder ED, et al. Phosphatidylinositol 3-kinase mediates bronchioalveolar stem cell expansion in mouse models of oncogenic K-ras-induced lung cancer. PLoS One. 2008; 3(5):e2220. Epub 2008/05/22. doi: 10.1371/journal.pone.0002220 PMID: 18493606; PubMed Central PMCID: PMC2376060.
34. Kolev VN, Wright QG, Vidal CM, Ring JE, Shapiro IM, Ricono J, et al. PI3K/mTOR dual inhibitor VS-5584 preferentially targets cancer stem cells. Cancer Res. 2015; 75(2):446-55. Epub 2014/11/30. doi: 10.1158/0008-5472.CAN-14-1223 [pii]. PMID: 25432176.
35. 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(4):436-48. Epub 2008/02/19. doi: 10.1101/gad. 1627008 22/4/436 [pii]. PMID: 18281460; PubMed Central PMCID: PMC2238666.
36. Hallahan AR, Pritchard JI, Hansen S, Benson M, Stoeck J, Hatton BA, et al. The SmoA1 mouse model reveals that notch signaling is critical for the growth and survival of sonic hedgehog-induced medulloblastomas. Cancer Res. 2004; 64(21):7794-800. Epub 2004/11/03. 64/21/7794 [pii] doi: 10.1158/0008-5472.CAN-04-1813 PMID: 15520185.
37. Emmenegger BA, Hwang EI, Moore C, Markant SL, Brun SN, Dutton JW, et al. Distinct roles for fibroblast growth factor signaling in cerebellar development and medulloblastoma. Oncogene. 2013; 32 (35):4181-8. Epub 2012/10/10. doi: 10.1038/onc.2012.440 [pii]. PMID: 23045271; PubMed Central PMCID: PMC3808889.
38. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. Epub 2005/10/04. 0506580102 [pii] doi: 10.1073/pnas. 0506580102 PMID: 16199517; PubMed Central PMCID: PMC1239896.
39. Singh AR, Joshi S, George E, Durden DL. Anti-tumor effect of a novel PI3-kinase inhibitor, SF1126, in (12) V-Ha-Ras transgenic mouse glioma model. Cancer Cell Int. 2014; 14(1):105. Epub 2014/11/27. doi: 10.1186/s12935-014-0105-9 [pii]. PMID: 25425962; PubMed Central PMCID: PMC4243316.
40. Maira SM, Stauffer F, Brueggen J, Furet P, Schnell C, Fritsch C, et al. Identification and characterization of NVP-BEZ235, a new orally available dual phosphatidylinositol 3-kinase/mammalian target of rapamycin inhibitor with potent in vivo antitumor activity. Mol Cancer Ther. 2008; 7(7):1851-63. Epub 2008/07/09. 1535-7163.MCT-08-0017 [pii] doi: 10.1158/1535-7163.MCT-08-0017 PMID: 18606717.
41. Yuan J, Mehta PP, Yin MJ, Sun S, Zou A, Chen J, et al. PF-04691502, a potent and selective oral inhibitor of PI3K and mTOR kinases with antitumor activity. Mol Cancer Ther. 2011; 10(11):2189-99. Epub 2011/07/14. 1535-7163.MCT-11-0185 [pii] doi: 10.1158/1535-7163.MCT-11-0185 PMID: 21750219.
42. Bendell JC, Rodon J, Burris HA, De Jonge M, Verweij J, Birle D, et al. Phase I, dose-escalation study of BKM120, an oral pan-Class I PI3K inhibitor, in patients with advanced solid tumors. J Clin Oncol. 2012; 30(3):282-90. Epub 2011/12/14. JCO.2011.36.1360 [pii] doi: 10.1200/JCO.2011.36.1360 PMID: 22162589.
43. Rutkowski S, Gerber NU, von Hoff K, Gnekow A, Bode U, Graf N, et al. Treatment of early childhood medulloblastoma by postoperative chemotherapy and deferred radiotherapy. Neuro Oncol. 2009; 11 (2):201-10. Epub 2008/09/27. doi: 10.1215/15228517-2008-084 [pii]. PMID: 18818397; PubMed Central PMCID: PMC2718992.
44. Broniscer A, Gururangan S, MacDonald TJ, Goldman S, Packer RJ, Stewart CF, et al. Phase I trial of single-dose temozolomide and continuous administration of o6-benzylguanine in children with brain tumors: A pediatric brain tumor consortium report. Clin Cancer Res. 2007; 13(22 Pt 1):6712-8. Epub 2007/11/17. 13/22/6712 [pii] doi: 10.1158/1078-0432.CCR-07-1016 PMID: 18006772.
45. Rodon J, Tawbi HA, Thomas AL, Stoller RG, Turtschi CP, Baselga J, et al. A phase I, multicenter, open-label, first-in-human, dose-escalation study of the oral smoothened inhibitor Sonidegib (LDE225) in patients with advanced solid tumors. Clin Cancer Res. 2014; 20(7):1900-9. Epub 2014/02/14. doi: 10.1158/1078-0432.CCR-13-1710 [pii]. PMID: 24523439.
46. Mayo LD, Donner DB. A phosphatidylinositol 3-kinase/Akt pathway promotes translocation of Mdm2 from the cytoplasm to the nucleus. Proc Natl Acad Sci U S A. 2001; 98(20):11598-603. Epub 2001/08/doi: 10.1073/pnas.181181198 [pii]. PMID: 11504915; PubMed Central PMCID: PMC58775.
47. Hoshida Y, Brunet JP, Tamayo P, Golub TR, Mesirov JP. Subclass mapping: Identifying common subtypes in independent disease data sets. PLoS One. 2007; 2(11):e1195. Epub 2007/11/22. doi: 10. 1371/journal.pone.0001195 PMID: 18030330; PubMed Central PMCID: PMC2065909.
48. Lamb J, Crawford ED, Peck D, Modell JW, Blat IC, Wrobel MJ, et al. The Connectivity Map: Using geneexpression signatures to connect small molecules, genes, and disease. Science. 2006; 313 (5795):1929-35. Epub 2006/09/30. 313/5795/1929 [pii] doi: 10.1126/science.1132939 PMID: 17008526.
49. Markant SL, Esparza LA, Sun J, Barton KL, McCoig LM, Grant GA, et al. Targeting sonic hedgehogassociated medulloblastoma through inhibition of Aurora and Polo-like kinases. Cancer Res. 2013; 73 (20):6310-22. Epub 2013/09/27. doi: 10.1158/0008-5472.CAN-12-4258 [pii]. PMID: 24067506; PubMed Central PMCID: PMC3800039.
50. Metcalfe C, Alicke B, Crow A, Lamoureux M, Dijkgraaf GJ, Peale F, et al. PTEN loss mitigates the response of medulloblastoma to Hedgehog pathway inhibition. Cancer Res. 2013; 73(23):7034-42. Epub 2013/10/25. doi: 10.1158/0008-5472.CAN-13-1222 [pii]. PMID: 24154871.
51. Inda MM, Mercapide J, Munoz J, Coullin P, Danglot G, Tunon T, et al. PTEN and DMBT1 homozygous deletion and expression in medulloblastomas and supratentorial primitive neuroectodermal tumors. Oncol Rep. 2004; 12(6):1341-7. Epub 2004/11/18. PMID: 15547761.
52. Pei Y, Moore CE, Wang J, Tewari AK, Eroshkin A, Cho YJ, et al.An animal model of MYC-driven medulloblastoma. Cancer Cell. 2012; 21(2):155-67. Epub 2012/02/22. doi: 10.1016/j.ccr.2011.12.021 S1535-6108(11)00483-1 [pii]. PMID: 22340590; PubMed Central PMCID: PMC3285431.
53. Poschl J, Stark S, Neumann P, Grobner S, Kawauchi D, Jones DT, et al. Genomic and transcriptomic analyses match medulloblastoma mouse models to their human counterparts. Acta Neuropathol. 2014; 128(1):123-36. Epub 2014/05/30. doi: 10.1007/s00401-014-1297-8 PMID: 24871706.
54. Genovesi LA, Ng CG, Davis MJ, Remke M, Taylor MD, Adams DJ, et al. Sleeping Beauty mutagenesis in a mouse medulloblastoma model defines networks that discriminate between human molecular subgroups. Proc Natl Acad Sci U S A. 2013; 110(46):E4325-34. Epub 2013/10/30. doi: 10.1073/pnas. 1318639110 [pii]. PMID: 24167280; PubMed Central PMCID: PMC3832011.
55. 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(4):465-72. Epub 2011/12/03. doi: 10.1007/s00401-011-0922-z PMID: 22134537; PubMed Central PMCID: PMC3306779.