Initial testing (stage 1) of AZD6244 (ARRY-142886) by the pediatric preclinical testing program

Pediatric Blood and Cancer

Volumn 55, Issue 4, 2010, Pages 668-677

  Kolb, E Anders ^a   Gorlick, Richard ^b   Houghton, Peter J ^c   Morton, Christopher L ^c   Neale, Geoffrey ^c   Keir, Stephen T ^d   Carol, Hernan ^e   Lock, Richard ^e   Phelps, Doris ^c   Kang, Min H ^f   Reynolds, C Patrick ^f   Maris, John M ^g   Billups, Catherine ^c   Smith, Malcolm A ^h  

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

^b CHILDREN S HOSPITAL AT MONTEFIORE   (United States)

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

^d DUKE UNIVERSITY MEDICAL CENTER   (United States)

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

^f CHILDREN S HOSPITAL LOS ANGELES   (United States)

^g UNIVERSITY OF PENNSYLVANIA   (United States)

^h NATIONAL CANCER INSTITUTE   (United States)

Author keywords

AZD6244; Developmental therapeutics; Preclinical testing

Indexed keywords

5 (4 BROMO 2 CHLOROANILINO) 4 FLUORO 1 METHYL 1H BENZIMIDAZOLE 6 CARBOHYDROXAMIC ACID 2 HYDROXYETHYL ESTER; B RAF KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; BENZIMIDAZOLE DERIVATIVE; MITOGEN ACTIVATED PROTEIN KINASE KINASE;

ACUTE LYMPHOBLASTIC LEUKEMIA; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; ASTROCYTOMA; CANCER INHIBITION; CANCER REGRESSION; CELL LINE; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; DRUG SCREENING; EPENDYMOMA; EWING SARCOMA; FEMALE; GLIOBLASTOMA; HUMAN; HUMAN CELL; IC 50; IMMUNOBLOTTING; IN VITRO STUDY; IN VIVO STUDY; MEDULLOBLASTOMA; MOUSE; MUTANT; NONHUMAN; OSTEOSARCOMA; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; RHABDOMYOSARCOMA; TUMOR VOLUME; XENOGRAFT; ANIMAL; BAGG ALBINO MOUSE; CHILD; DRUG ANTAGONISM; GENETICS; MUTATION; NEOPLASM;

ANIMALS; BENZIMIDAZOLES; CHILD; DRUG SCREENING ASSAYS, ANTITUMOR; FEMALE; HUMANS; MICE; MICE, INBRED BALB C; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MUTATION; NEOPLASMS; PROTO-ONCOGENE PROTEINS B-RAF; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 77957071661     PISSN: 15455009     EISSN: 15455017     Source Type: Journal    
DOI: 10.1002/pbc.22576     Document Type: Article

References (33)

1. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer. Nature 2002; 417: 949-954.
2. Garnett MJ, Marais R. Guilty as charged: B-RAF is a human oncogene. Cancer Cell 2004; 6: 313-319.
3. Miao J, Kusafuka T, Fukuzawa M. Hotspot mutations of BRAF gene are not associated with pediatric solid neoplasms. Oncol Rep 2004; 12: 1269-1272.
4. Gilbertson RJ, Langdon JA, Hollander A, et al. Mutational analysis of PDGFR-RAS/MAPK pathway activation in childhood medulloblastoma. Eur J Cancer 2006; 42: 646-649.
5. Gustafsson B, Angelini S, Sander B, et al. Mutations in the BRAF and N-ras genes in childhood acute lymphoblastic leukaemia. Leukemia 2005; 19: 310-312.
6. Case M, Matheson E, Minto L, et al. Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia. Cancer Res 2008; 68: 6803-6809.
7. Jones DT, Kocialkowski S, Liu L, et al. Tandem duplication producing a novel oncogenic BRAF fusion gene defines the majority of pilocytic astrocytomas. Cancer Res 2008; 68: 8673-8677.
8. Jones DT, Kocialkowski S, Liu L, et al. Oncogenic RAF1 rearrangement and a novel BRAF mutation as alternatives to KIAA1549: BRAF fusion in activating the MAPK pathway in pilocytic astrocytoma. Oncogene 2009; 28: 2119-2123.
9. Pfister S, Janzarik WG, Remke M, et al. BRAF gene duplication constitutes a mechanism of MAPK pathway activation in low-grade astrocytomas. J Clin Invest 2008; 118: 1739-1749.
10. Forshew T, Tatevossian RG, Lawson AR, et al. Activation of the ERK/MAPK pathway: A signature genetic defect in posterior fossa pilocytic astrocytomas. J Pathol 2009; 218: 172-181.
11. Solit DB, Garraway LA, Pratilas CA, et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature 2006; 439: 358-362.
12. Wan PT, Garnett MJ, Roe SM, et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 2004; 116: 855-867.
13. Davies BR, Logie A, McKay JS, et al. AZD6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: Mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther 2007; 6: 2209-2219.
14. Yeh TC, Marsh V, Bernat BA, et al. Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1/2 inhibitor. Clin Cancer Res 2007; 13: 1576-1583.
15. Adjei AA, Cohen RB, Franklin W, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral, small-molecule mitogen-activated protein kinase kinase 1/2 inhibitor AZD6244 (ARRY-142886) in patients with advanced cancers. J Clin Oncol 2008; 26: 2139-2146.
16. Banerji U, Camidge DR, Verheul HM, et al. The first-in-human study of the hydrogen sulfate (Hyd-sulfate) capsule of the MEK1/2 inhibitor AZD6244 (ARRY-142886): A phase I open-label multicenter trial in patients with advanced cancer. Clin Cancer Res 16: 1613-1623.
17. 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.
18. Houghton PJ, Morton CL, Kolb EA, et al. Initial testing (stage 1) of the proteasome inhibitor bortezomib by the pediatric preclinical testing program. Pediatr Blood Cancer 2008; 50: 37-45.
19. Friedman HS, Colvin OM, Skapek SX, et al. Experimental chemotherapy of human medulloblastoma cell lines and transplantable xenografts with bifunctional alkylating agents. Cancer Res 1988; 48: 4189-4195.
20. Graham C, Tucker C, Creech J, et al. Evaluation of the antitumor efficacy, pharmacokinetics, and pharmacodynamics of the histone deacetylase inhibitor depsipeptide in childhood cancer models in vivo. Clin Cancer Res 2006; 12: 223-234.
21. Peterson JK, Tucker C, Favours E, et al. In vivo evaluation of ixabepilone (BMS247550), a novel epothilone B derivative, against pediatric cancer models. Clin Cancer Res 2005; 11: 6950-6958.
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. Houghton PJ, Morton CL, Tucker C, et al. The pediatric preclinical testing program: Description of models and early testing results. Pediatr Blood Cancer 2007; 49: 928-940.
24. 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.
25. Beghini A, Magnani I, Ripamonti CB, et al. Amplification of a novel c-Kit activating mutation Asn(822)-Lys in the Kasumi-1 cell line: A t(8;21)-Kit mutant model for acute myeloid leukemia. Hematol J 2002; 3: 157-163.
26. Dam V, Morgan BT, Mazanek P, et al. Mutations in PIK3CA are infrequent in neuroblastoma. BMC Cancer 2006; 6: 177.
27. Knobbe CB, Reifenberger J, Reifenberger G. Mutation analysis of the Ras pathway genes NRAS, HRAS, KRAS and BRAF in glioblastomas. Acta Neuropathol 2004; 108: 467-470.
28. Jones DT, Kocialkowski S, Liu L, et al. A novel oncogenic fusion gene is found in the majority of pilocytic astrocytomas. Proceedings of the 99th Annual Meeting of the American Association for Cancer Research 2008.
29. Emery CM, Vijayendran KG, Zipser MC, et al. MEK1 mutations confer resistance to MEK and B-RAF inhibition. Proc Natl Acad Sci USA 2009; 106: 20411-20416.
30. Wee S, Jagani Z, Xiang KX, et al. PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers. Cancer Res 2009; 69: 4286-4293.
31. Legrier ME, Yang CP, Yan HG, et al. Targeting protein translation in human non small cell lung cancer via combined MEK and mammalian target of rapamycin suppression. Cancer Res 2007; 67: 11300-11308.
32. Sambade MJ, Camp JT, Kimple RJ, et al. Mechanism of lapatinib-mediated radiosensitization of breast cancer cells is primarily by inhibition of the Raf > MEK > ERK mitogen-activated protein kinase cascade and radiosensitization of lapatinib-resistant cells restored by direct inhibition of MEK. Radiother Oncol 2009; 93: 639-644.
33. Haass NK, Sproesser K, Nguyen TK, et al. The mitogen-activated protein/extracellular signal-regulated kinase kinase inhibitor AZD6244 (ARRY-142886) induces growth arrest in melanoma cells and tumor regression when combined with docetaxel. Clin Cancer Res 2008; 14: 230-239.