Initial testing (stage 1) of the phosphatidylinositol 3′ kinase inhibitor, SAR245408 (XL147) by the pediatric preclinical testing program

Pediatric Blood and Cancer

Volumn 60, Issue 5, 2013, Pages 791-798

  Reynolds, C Patrick ^a   Kang, Min H ^a   Carol, Hernan ^b   Lock, Richard ^b   Gorlick, Richard ^c   Kolb, E Anders ^d   Kurmasheva, Raushan T ^e   Keir, Stephen T ^f   Maris, John M ^g   Billups, Catherine A ^h   Houghton, Peter J ^e   Smith, Malcolm A ⁱ  

^a TEXAS TECH UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b CHILDREN S CANCER INSTITUTE AUSTRALIA FOR MEDICAL RESEARCH   (Australia)

^c CHILDREN S HOSPITAL AT MONTEFIORE   (United States)

^d NEMOURS ALFRED I DUPONT HOSPITAL FOR CHILDREN   (United States)

^e NATIONWIDE CHILDREN S HOSPITAL   (United States)

^f DUKE UNIVERSITY MEDICAL CENTER   (United States)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

^h ST JUDE CHILDREN S RESEARCH HOSPITAL   (United States)

ⁱ NATIONAL CANCER INSTITUTE   (United States)

Author keywords

Developmental therapeutics; PI3K inhibitor; Preclinical testing

Indexed keywords

XL 147;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ARTICLE; BRAIN TUMOR; CANCER CELL CULTURE; CANCER INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG CYTOTOXICITY; DRUG EFFICACY; DRUG SCREENING; DRUG TOLERABILITY; EWING SARCOMA; FEMALE; GLIOMA; HUMAN; HUMAN CELL; IC 50; IN VITRO STUDY; IN VIVO STUDY; KIDNEY TUMOR; MOUSE; NEUROBLASTOMA; NONHUMAN; OSTEOSARCOMA; PRIORITY JOURNAL; RHABDOID TUMOR; RHABDOMYOSARCOMA; SOLID TUMOR; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HUMANS; MICE; MICE, INBRED BALB C; MICE, INBRED NOD; MICE, NUDE; NEOPLASM TRANSPLANTATION; NEOPLASMS; PHOSPHATIDYLINOSITOL 3-KINASES; QUINOXALINES; SULFONAMIDES; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84874999558     PISSN: 15455009     EISSN: 15455017     Source Type: Journal    
DOI: 10.1002/pbc.24301     Document Type: Article

References (43)

1. Courtney KD, Corcoran RB, Engelman JA. The PI3K pathway as drug target in human cancer. J Clin Oncol 2010;28:1075-1083.
2. Hennessy BT, Smith DL, Ram PT, et al. Exploiting the PI3K/AKT pathway for cancer drug discovery. Nat Rev Drug Discov 2005;4:988-1004.
3. Luo J, Manning BD, Cantley LC. Targeting the PI3K-Akt pathway in human cancer: Rationale and promise. Cancer Cell 2003;4:257-262.
4. Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489-501.
5. Markman B, Dienstmann R, Tabernero J. Targeting the PI3K/Akt/mTOR pathway-beyond rapalogs. Oncotarget 2010;1:530-543.
6. Manning BD, Cantley LC. AKT/PKB signaling: Navigating downstream. Cell 2007;129:1261-1274.
7. Shor B, Gibbons JJ, Abraham RT, et al. Targeting mTOR globally in cancer: Thinking beyond rapamycin. Cell Cycle 2009;8:3831-3837.
8. Samuels Y, Wang Z, Bardelli A, et al. High frequency of mutations of the PIK3CA gene in human cancers. Science 2004;304:554.
9. Georgescu MM. PTEN Tumor suppressor network in PI3K-Akt pathway control. Genes Cancer 2010;1:1170-1177.
10. Keniry M, Parsons R. The role of PTEN signaling perturbations in cancer and in targeted therapy. Oncogene 2008;27:5477-5485.
11. Engelman JA, Luo J, Cantley LC. The evolution of phosphatidylinositol 3-kinases as regulators of growth and metabolism. Nat Rev Genet 2006;7:606-619.
12. Chakrabarty A, Sanchez V, Kuba MG, et al. Feedback upregulation of HER3 (ErbB3) expression and activity attenuates antitumor effect of PI3K inhibitors Proc Natl Acad Sci USA 2011.
13. Edelman G, Bedell C, Shapiro Gea. A phase I dose-escalation study of XL147 (SAR 245408), a P13K inhibitor administred orally to patients (pts) with advanced malignancies. J Clin Oncol 2010;28:3003.
14. Houghton PJ, Morton CL, Kolb EA, et al. Initial testing (stage 1) of the mTOR inhibitor rapamycin by the pediatric preclinical testing program. Pediatr Blood Cancer 2008;50:799-7805.
15. Houghton PJ, Morton CL, Gorlick R, et al. Stage 2 combination testing of rapamycin with cytotoxic agents by the pediatric preclinical testing program. Mol Cancer Ther 2010;9:101-112.
16. Houghton PJ, Gorlick R, Kolb EA, et al. Initial testing (stage 1) of the mTOR kinase inhibitor AZD8055 by the pediatric preclinical testing program. Pediatr Blood Cancer 2012;58:191-199.
17. Carol H, Morton CL, Gorlick R, et al. Initial testing (stage 1) of the Akt inhibitor GSK 690693 by the pediatric preclinical testing program. Pediatr Blood Cancer 2010;55:1329-1337.
18. Gorlick R, Maris JM, Houghton PJ, et al. Testing of the Akt/PKB inhibitor MK-2206 by the pediatric preclinical testing program. Pediatr Blood Cancer 2011.
19. Frgala T, Kalous O, Proffitt RT, et al. A fluorescence microplate cytotoxicity assay with a 4-log dynamic range that identifies synergistic drug combinations. Mol Cancer Ther 2007;6:886-897.
20. Kang MH, Smith MA, Morton CL, et al. National Cancer Institute Pediatric Preclinical Testing Program: Model description for in vitro cytotoxicity testing. Pediatr Blood Cancer 2011;56:239-249.
21. Houghton PJ, Morton CL, Tucker C, et al. The pediatric preclinical testing program: Description of models and early testing results. Pediatr Blood Cancer 2006.
22. Liem NL, Papa RA, Milross CG, et al. Characterization of childhood acute lymphoblastic leukemia xenograft models for the preclinical evaluation of new therapies. Blood 2004;103:3905-3914.
23. Kurmasheva RT, Harwood FC, Houghton PJ. Differential regulation of vascular endothelial growth factor by Akt and mammalian target of rapamycin inhibitors in cell lines derived from childhood solid tumors. Mol Cancer Ther 2007;6:1620-1628.
24. Vanhaesebroeck B, Welham MJ, Kotani K, et al. P110delta, a novel phosphoinositide 3-kinase in leukocytes. Proc Nat Acad Sci USA 1997;94:4330-4335.
25. Shapiro GI, Edelman G, Calvo E, et al. Targeting aberrant PI3K pathway signaling with XL147, a potent, selective and orally bioavailable PI3K inhibitor. AACR-NCI-EORTC International Conference 2007: Abstr C205.
26. Lannutti BJ, Meadows SA, Herman SE, et al. CAL-101, a p110delta selective phosphatidylinositol-3-kinase inhibitor for the treatment of B-cell malignancies, inhibits PI3K signaling and cellular viability. Blood 2011;117:591-594.
27. Coutre SE, Byrd JC, Furman RR, et al. Phase I study of CAL-101, an isoform-selective inhibitor of phosphatidylinositol 3-kinase P110d, in patients with previously treated chronic lymphocytic leukemia. J Clin Oncol 2011;29 (suppl; abstr 3064).
28. Osaki M, Oshimura M, Ito H. PI3K-Akt pathway: Its functions and alterations in human cancer. Apoptosis: Int J Program Cell Death 2004;9:667-676.
29. Petricoin EF III, Espina V, Araujo RP, et al. Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival. Cancer Res 2007;67:3431-3440.
30. Opel D, Poremba C, Simon T, et al. Activation of Akt predicts poor outcome in neuroblastoma. Cancer Res 2007;67:735-745.
31. Boller D, Schramm A, Doepfner KT, et al. Targeting the phosphoinositide 3-kinase isoform p110delta impairs growth and survival in neuroblastoma cells. Clin Cancer Res 2008;14:1172-1181.
32. Segerstrom L, Baryawno N, Sveinbjornsson B, et al. Effects of small molecule inhibitors of PI3K/Akt/mTOR signaling on neuroblastoma growth in vitro and in vivo. Int J Cancer 2011;129:2958-2965.
33. Guerreiro AS, Fattet S, Fischer B, et al. Targeting the PI3K p110alpha isoform inhibits medulloblastoma proliferation, chemoresistance, and migration. Clin Cancer Res 2008;14:6761-6769.
34. Buonamici S, Williams J, Morrissey M, et al. Interfering with resistance to smoothened antagonists by inhibition of the PI3K pathway in medulloblastoma. Sci Transl Med 2010;2:51ra70.
35. Guerreiro AS, Fattet S, Kulesza DW, et al. A sensitized RNA interference screen identifies a novel role for the PI3K p110gamma isoform in medulloblastoma cell proliferation and chemoresistance. Mol Cancer Res 2011;9:925-935.
36. Morozova O, Birol I, Corbett R, et al. Whole genome and transcriptome sequencing defines the spectrum of somatic changes in high-risk neuroblastoma. Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research 2011: Abstr 926.
37. Pugh TJ, Lawrence M, Sougnez C, et al. Exome sequencing of 81 neuroblastomas identifies a wide diversity of somatic mutation. Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research 2011: Abstr 4756.
38. Zhang J, Mullighan CG, Harvey RC, et al. Key pathways are frequently mutated in high risk childhood acute lymphoblastic leukemia: A report from the Children's Oncology group. Blood 2011.
39. Shukla N, Ameur N, Yilmaz I, et al. Oncogene mutation profiling of pediatric solid tumors reveals significant subsets of embryonal rhabdomyosarcoma and neuroblastoma with mutated genes in growth signaling pathways. Clin Cancer Res 2012.
40. Broderick DK, Di C, Parrett TJ, et al. Mutations of PIK3CA in anaplastic oligodendrogliomas, high-grade astrocytomas, and medulloblastomas. Cancer Res 2004;64:5048-5050.
41. Pugh TJ, Cho YJ, Archer T, et al. Medulloblastoma exome sequencing uncovers subtype-specific somatic mutations within a wide spectrum of genetic heterogeneity. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research 2012.
42. Jones DT, Jaeger N, Cho YJ, et al. ICGC PedBrain tumor-next-generation sequencing identifies novel subgroup-specific mutations and copy number aberrations in medulloblastoma. Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research 2012: Abstr # 4872.
43. Bender A, Opel D, Naumann I, et al. PI3K inhibitors prime neuroblastoma cells for chemotherapy by shifting the balance towards pro-apoptotic Bcl-2 proteins and enhanced mitochondrial apoptosis. Oncogene 2011;30:494-503.