Synergistic action of a RAF inhibitor and a dual PI3K/mTOR inhibitor in thyroid cancer

Clinical Cancer Research

Volumn 17, Issue 20, 2011, Pages 6482-6489

  Jin, Ning ^a   Jiang, Tianyun ^a   Rosen, David M ^a   Nelkin, Barry D ^a   Ball, Douglas W ^a,b  

^a JOHNS HOPKINS UNIVERSITY   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (1 CYANO 1 METHYLETHYL) 3 METHYL 8 (3 QUINOLINYL)IMIDAZO[4,5 C]QUINOLIN 2(1H,3H) ONE; CHIR 265; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN RET; RAF PROTEIN; TORC1 PROTEIN; TORC2 PROTEIN; TUMOR PROTEIN; UNCLASSIFIED DRUG; VASCULOTROPIN RECEPTOR 2;

ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAF GENE; CANCER CELL; CANCER INHIBITION; CELL CYCLE ARREST; CONTROLLED STUDY; DRUG POTENCY; DRUG POTENTIATION; DRUG TARGETING; ENZYME INHIBITION; FEMALE; GENE MUTATION; IC 50; MOUSE; NONHUMAN; ONCOGENE RAS; PRIORITY JOURNAL; PTEN GENE; RET GENE; THYROID CANCER; TUMOR XENOGRAFT;

ANIMALS; ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; CELL CYCLE; CELL LINE, TUMOR; DRUG SYNERGISM; FEMALE; HUMANS; IMIDAZOLES; MICE; MICE, NUDE; PHOSPHATIDYLINOSITOL 3-KINASE; PROTO-ONCOGENE PROTEINS B-RAF; PYRIDINES; QUINOLINES; SIGNAL TRANSDUCTION; THYROID NEOPLASMS; TOR SERINE-THREONINE KINASES; TRANSPLANTATION, HETEROLOGOUS;

EID: 80054118460     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-11-0933     Document Type: Article

References (31)

1. Jemal A, Siegel R, Xu J, Ward E. Cancer statistics, 2010. CA Cancer J Clin 2010;60:277-300.
2. Durante C, Puxeddu E, Ferretti E, Morisi R, Moretti S, Bruno R, et al. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J Clin Endocrinol Metab 2007;92:2840-3. (Pubitemid 47037399)
3. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol 2010;321:86-93.
4. Knauf JA, Fagin JA. Role of MAPK pathway oncoproteins in thyroid cancer pathogenesis and as drug targets. Curr Opin Cell Biol 2009; 21:296-303.
5. Xing M. Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer. Thyroid 2010;20:697-706.
6. Saji M, Ringel MD. The PI3K-Akt-mTOR pathway in initiation and progression of thyroid tumors. Mol Cell Endocrinol 2010;321:20-8.
7. Elisei R, Cosci B, Romei C, Bottici V, Renzini G, Molinaro E, et al. Prognostic significance of somatic RET oncogene mutations in sporadic medullary thyroid cancer: a 10-year follow-up study. J Clin Endocrinol Metab 2008;93:682-7. (Pubitemid 351398539)
8. Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, et al. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol 2010;11:962-72.
9. Wells SA, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, et al. Vandetanib (VAN) in locally advanced or metastatic medullary thyroid cancer (MTC): a randomized, double-blind phase III trial (ZETA). J Clin Oncol 2010;28 Suppl:abstr 5503.
10. Schlumberger M. Kinase inhibitors for refractory thyroid cancers. Lancet Oncol 2010;11:912-3.
11. Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, et al. Activity of XL184 (cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol 2011;29:2660-6.
12. Salerno P, Falco VD, Tamburino A, Nappi T, Vecchio G, Schweppe R, et al. Cytostatic activity of ATP-competitive kinase inhibitors in BRAF mutant thyroid carcinoma cells. J Clin Endocrinol Metab 2009;95: 450-5.
13. Flaherty KT, Puzanov I, Kim KB, Ribas A, McArthur GA, Sosman JA, et al. Inhibition of mutated, activated BRAF in metastatic melanoma. N Engl J Med 2010;363:809-19.
14. Ball DW. Selectively targeting mutant BRAF in thyroid cancer. J Clin Endocrinol Metab 2010;95:60-1.
15. Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wildtype BRAF. Nature 2010;464:427-30.
16. 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;7:1851-63.
17. Serra V, Markman B, Scaltriti M, Eichhorn PJ, Valero V, Guzman M, et al. NVP-BEZ235, a dual PI3K/mTOR inhibitor, prevents PI3K signaling and inhibits the growth of cancer cells with activating PI3K mutations. Cancer Res 2008;68:8022-30.
18. Brachmann SM, Hofmann I, Schnell C, Fritsch C, Wee S, Lane H, et al. Specific apoptosis induction by the dual PI3K/mTor inhibitor NVPBEZ235 in HER2 amplified and PIK3CA mutant breast cancer cells. Proc Natl Acad Sci U S A 2009;106:22299-304.
19. Burris H. First-in-human phase I study of the oral PI3K inhibitor BEZ235 in patients (pts) with advanced solid tumors. J Clin Oncol 2010;28:3005.
20. Venetsanakos E, Stuart D, Tan N, Ye H, Salangsang F, Aardalen K, et al. CIR-265, a novel inhibitor that targets B-RAF and VEGFR, shows efficacy in a broad range of preclinical models. Proc Am Assoc Cancer Res 2006;47:1140.
21. Mordant P, Loriot Y, Leteur C, Calderaro J, Bourhis J, Wislez M, et al. Dependence on phosphoinositide 3-kinase and RAS-RAF pathways drive the activity of RAF265, a novel RAF/VEGFR2 inhibitor, and RAD001 (Everolimus) in combination. Mol Cancer Ther 2010;9: 358-68.
22. Sharfman W, Hodi F, Lawrence DP, Flaherty K, Amaravadi R, Kim K, et al. Results from the first-in-human (FIH) phase I study of the oral RAF inhibitor RAF265 administered daily to patients with advanced cutaneous melanoma. J Clin Oncol 2011;29:abstr 8508.
23. Chou TC, Talalay P. Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 1984;22:27-55.
24. Carlomagno F, Anaganti S, Guida T, Salvatore G, Troncone G, Wilhelm SM, et al. BAY 43-9006 inhibition of oncogenic RET mutants. J Natl Cancer Inst 2006;98:326-34. (Pubitemid 43338212)
25. Jin N, Jiang T, Rosen DM, Nelkin BD, Ball DW. Dual inhibition of mitogen-activated protein kinase kinase and mammalian target of rapamycin in differentiated and anaplastic thyroid cancer. J Clin Endocrinol Metab 2009;94:4107-12.
26. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, et al. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nat Med 2008; 14:1351-6.
27. Gopal YN, Deng W, Woodman SE, Komurov K, Ram P, Smith PD, et al. Basal and treatment-induced activation of AKT mediates resistance to cell death by AZD6244 (ARRY-142886) in Braf-mutant human cutaneous melanoma cells. Cancer Res 2010;70:8736-47.
28. Carracedo A, Ma L, Teruya-Feldstein J, Rojo F, Salmena L, Alimonti A, et al. Inhibition of mTORC1 leads to MAPK pathway activation through a PI3K-dependent feedback loop in human cancer. J Clin Invest 2008;118:3065-74.
29. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, et al. 4EBP1 is a key effector of the oncogenic activation of the AKT and ERK signaling pathways that integrates their function in tumors. Cancer Cell 2010;18:39-51.
30. Faber AC, Li D, Song Y, Liang MC, Yeap BY, Bronson RT, et al. Differential induction of apoptosis in HER2 and EGFR addicted cancers following PI3K inhibition. Proc Natl Acad Sci U S A 2009; 106:19503-8.
31. Zitzmann K, Ruden J, Brand S, Goke B, Lichtl J, Spottl G, et al. Compensatory activation of Akt in response to mTOR and Raf inhibitors-a rationale for dual-targeted therapy approaches in neuroendocrine tumor disease. Cancer Lett 2010;295: 100-9.