Preclinical therapeutic synergy of MEK1/2 and CDK4/6 inhibition in neuroblastoma

Clinical Cancer Research

Volumn 23, Issue 7, 2017, Pages 1785-1796

  Hart, Lori S ^a   Rader, JulieAnn ^a   Raman, Pichai ^a   Batra, Vandana ^a   Russell, Mike R ^a   Tsang, Matthew ^a   Gagliardi, Maria ^a   Chen, Lucy ^a   Martinez, Daniel ^a   Li, Yimei ^a,b   Wood, Andrew ^a   Kim, Sunkyu ^c   Parasuraman, Sudha ^c   Delach, Scott ^c   Cole, Kristina A ^a,b   Krupa, Shiva ^d   Boehm, Markus ^d   Peters, Malte ^d   Caponigro, Giordano ^c   Maris, John M ^a,b,e  

^a CHILDREN S HOSPITAL OF PHILADELPHIA   (United States)

^b UNIVERSITY OF PENNSYLVANIA   (United States)

^c NOVARTIS INSTITUTES FOR BIOMEDICAL RESEARCH   (United States)

^d NOVARTIS PHARMA AG   (Switzerland)

^e UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINIMETINIB; CYCLIN DEPENDENT KINASE 4; CYCLIN DEPENDENT KINASE 6; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 2; RIBOCICLIB; BENZIMIDAZOLE DERIVATIVE; PROTEIN KINASE INHIBITOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER INHIBITION; CELL CYCLE ASSAY; CELL CYCLE REGULATION; CELL PROLIFERATION ASSAY; DISEASE ASSOCIATION; DRUG EFFECT; DRUG RESISTANCE; DRUG SENSITIVITY; ENZYME INHIBITION; FEMALE; GENE; GENE AMPLIFICATION; GENE EXPRESSION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; MICROSCOPY; MYCN GENE; NEUROBLASTOMA; NEUROBLASTOMA CELL LINE; NONHUMAN; SIGNAL TRANSDUCTION; TIME LAPSE IMAGING; TUMOR XENOGRAFT; ANIMAL; APOPTOSIS; CELL PROLIFERATION; DRUG EFFECTS; DRUG SCREENING; GENETICS; MAPK SIGNALING; MOUSE; PATHOLOGY; PHOSPHORYLATION; TUMOR RECURRENCE;

ANIMALS; APOPTOSIS; BENZIMIDAZOLES; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; HUMANS; MAP KINASE SIGNALING SYSTEM; MICE; NEOPLASM RECURRENCE, LOCAL; NEUROBLASTOMA; PHOSPHORYLATION; PROTEIN KINASE INHIBITORS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 85017031088     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-16-1131     Document Type: Article

References (32)

1. Smith MA, Seibel NL, Altekruse SF, Ries LA, Melbert DL, O'Leary M, et al. Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 2010;28:2625-34.
2. Maris JM. Recent advances in neuroblastoma. N Engl J Med 2010;362: 2202-11.
3. Easton J, Wei T, Lahti JM, Kidd VJ. Disruption of the Cyclin D/cyclindependent kinase/INK4/retinoblastoma protein regulatory pathway in human neuroblastoma. Cancer Res 1998;58:2624-32.
4. Krasnoselsky AL, Whiteford CC, Wei JS, Bilke S, Westermann F, Chen Q-R, et al. Altered expression of cell cycle genes distinguishes aggressive neuroblastoma. Oncogene 2004;24:1533-41.
5. Molenaar JJ, Ebus ME, Koster J, Sluis PV, van Noesel CJM, Versteeg R, et al. Cyclin D1 and CDK4 activity contribute to the undifferentiated phenotype in neuroblastoma. Cancer Res 2008;68:2599-09.
6. Molenaar JJ, Koster J, Ebus ME, van Sluis P, Westerhout EM, de Preter K, et al. Copy number defects of G1-cell cycle genes in neuroblastoma are frequent and correlate with high expression of E2F target genes and a poor prognosis. Genes Chromosomes Cancer 2012;51:10-9.
7. Molenaar JJ, van Sluis P, Boon K, Versteeg R, Caron HN. Rearrangements and increased expression of cyclin D1 (CCND1) in neuroblastoma. Genes Chromosomes Cancer 2003;36:242-9.
8. Mosse YP, Diskin SJ, Wasserman N, Rinaldi K, Attiyeh EF, Cole K, et al. Neuroblastomas have distinct genomic DNA profiles that predict clinical phenotype and regional gene expression. Genes Chromosomes Cancer 2007;46:936-49.
9. Cole KA, Huggins J, Laquaglia M, Hulderman CE, Russell MR, Bosse K, et al. RNAi screen of the protein kinome identifies checkpoint kinase 1 (CHK1) as a therapeutic target in neuroblastoma. Proc Natl Acad Sci 2011;108: 3336-41.
10. Rader J, Russell MR, Hart LS, Nakazawa MS, Belcastro LT, Martinez D, et al. Dual CDK4/CDK6 inhibition induces cell-cycle arrest and senescence in neuroblastoma. Clin Cancer Res 2013;19:6173-82.
11. Pugh TJ, Morozova O, Attiyeh EF, Asgharzadeh S, Wei JS, Auclair D, et al. The genetic landscape of high-risk neuroblastoma. Nat Genet 2013;45: 279-84.
12. Schleiermacher G, Javanmardi N, Bernard V, Leroy Q, Cappo J, Rio Frio T, et al. Emergence of new ALK mutations at relapse of neuroblastoma. J Clin Oncol 2014;32:2727-34.
13. Eleveld TF, Oldridge DA, Bernard V, Koster J, Daage LC, Diskin SJ, et al. Relapsed neuroblastomas show frequent RAS-MAPK pathway mutations. Nat Genet 2015;47:864-71.
14. Russell MR, Levin K, Rader J, Belcastro L, Li Y, Martinez D, et al. Combination therapy targeting the Chk1 and wee1 kinases shows therapeutic efficacy in neuroblastoma. Cancer Res 2013;73:776-84.
15. Chou T, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
16. Lehàr J, Krueger AS, Avery W, Heilbut AM, Johansen LM, Price ER, et al. Synergistic drug combinations improve therapeutic selectivity. Nat Biotechnol 2009;27:659-66.
17. Quah BJC, Parish CR. The use of carboxyfluorescein diacetate succinimidyl ester (CFSE) to monitor lymphocyte proliferation. J Vis Exp 2010:2259.
18. Batra V, Maris JM, Kang MH, Reynolds CP, Houghton PJ, Alexander D, et al. Initial Testing (Stage 1) of SGI-1776, a PIM1 Kinase Inhibitor, by the Pediatric Preclinical Testing Program. Pediatric Blood Cancer 2012;59: 749-52.
19. Keshelava N, Houghton PJ, Morton CL, Lock RB, Carol H, Keir ST, et al. Initial testing (Stage 1) of vorinostat (SAHA) by the pediatric preclinical testing program. Pediat Blood Cancer 2009;53:505-8.
20. Wood AC, Maris JM, Gorlick R, Kolb EA, Keir ST, Reynolds CP, et al. Initial testing (Stage 1) of the antibody-maytansinoid conjugate, IMGN901 (Lorvotuzumab Mertansine), by the pediatric preclinical testing program. Pediat Blood Cancer 2013;60:1860-7.
21. Frampton GM, Fichtenholtz A, Otto GA, Wang K, Downing SR, He J, et al. Development and validation of a clinical cancer genomic profiling test based on massively parallel DNA sequencing. Nat Biotechnol 2013;31: 1023-31.
22. Atienza JM, Zhu J, Wang X, Xu X, Abassi Y. Dynamic monitoring of cell adhesion and spreading on microelectronic sensor arrays. J Biomol Screen 2005;10:795-805.
23. Woodfield SE, Zhang L, Scorsone KA, Liu Y, Zage PE. Binimetinib inhibits MEK and is effective against neuroblastoma tumor cells with low NF1 expression. BMC Cancer 2016;16:1-10.
24. Baranski Z, Booij TH, Kuijjer ML, de Jong Y, Cleton-Jansen A-M, Price LS, et al. MEK inhibition induces apoptosis in osteosarcoma cells with constitutive ERK1/2 phosphorylation. Genes Cancer 2015; 6:503-12.
25. Fredlund E, Ringnér M, Maris JM, Påhlman S. High Myc pathway activity and low stage of neuronal differentiation associate with poor outcome in neuroblastoma. Proc Natl Acad Sci 2008;105:14094-9.
26. Valentijn LJ, Koster J, Haneveld F, Aissa RA, van Sluis P, Broekmans ME, et al. Functional MYCN signature predicts outcome in neuroblastoma irrespective of MYCN amplification. Proc Natl Acad Sci 2012;109: 19190-5.
27. Ziemke EK, Dosch JS, Maust JD, Shettigar A, Sen A, Welling TH, et al. Sensitivity of KRAS-mutant colorectal cancers to combination therapy that cotargets MEK and CDK4/6. Clin Cancer Res 2016;22: 405-14.
28. Franco J, Witkiewicz AK, Knudsen ES. CDK4/6 inhibitors have potent activity in combination with pathway selective therapeutic agents in models of pancreatic cancer. Oncotarget 2014;5:6512-25.
29. Lee MS, Helms TL, Feng N, Gay J, Chang QE, Tian F, et al. Efficacy of the combination of MEK and CDK4/6 inhibitors in vitro and in vivo in KRAS mutant colorectal cancer models. Oncotarget 2016;7: 39595-608.
30. Yu AL, Gilman AL, Ozkaynak MF, London WB, Kreissman SG, Chen HX, et al. Anti-GD2 antibody with GM-CSF, interleukin-2, and isotretinoin for neuroblastoma. The N Engl J Med 2010;363: 1324-34.
31. Diskin SJ, Capasso M, Diamond M, Oldridge DA, Conkrite K, Bosse KR, et al. Rare variants in TP53 and susceptibility to neuroblastoma. J Natl Cancer Inst 2014;106:1-4.
32. Valentijn LJ, Koster J, Zwijnenburg DA, Hasselt NE, van Sluis P, Volckmann R, et al. TERT rearrangements are frequent in neuroblastoma and identify aggressive tumors. Nat Genet 2015;47:1411-4.