The broad-spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF-mutant melanoma cells in combination with other signaling pathway inhibitors

Pigment Cell and Melanoma Research

Volumn 28, Issue 4, 2015, Pages 417-430

  Langdon, Casey G ^a   Held, Matthew A ^a,b   Platt, James T ^a   Meeth, Katrina ^a   Iyidogan, Pinar ^a   Mamillapalli, Ramanaiah ^a   Koo, Andrew B ^a   Klein, Michael ^a   Liu, Zongzhi ^a   Bosenberg, Marcus W ^a   Stern, David F ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b HARVARD MEDICAL SCHOOL   (United States)

Author keywords

Combination therapy; Dovitinib; MEK inhibitor; Mutant BRAF; Vemurafenib resistance

Indexed keywords

1,4 DIAMINO 1,4 BIS(2 AMINOPHENYLTHIO) 2,3 DICYANOBUTADIENE; 2 [4 (1 HYDROXYIMINO 5 INDANYL) 3 (4 PYRIDINYL) 1H PYRAZOL 1 YL]ETHANOL; 8 [4 (1 AMINOCYCLOBUTYL)PHENYL] 9 PHENYL 1,2,4 TRIAZOLO[3,4 F][1,6]NAPHTHYRIDIN 3(2H) ONE; B RAF KINASE; B RAF KINASE INHIBITOR; CIP 1374; DABRAFENIB; DOVITINIB; EPIGALLOCATECHIN GALLATE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; N [3 (5 CHLORO 1H PYRROLO[2,3 B]PYRIDINE 3 CARBONYL) 2,4 DIFLUOROPHENYL]PROPANESULFONAMIDE; POLYPHENOL; PROTEIN KINASE B INHIBITOR; SELUMETINIB; TRAMETINIB; UNCLASSIFIED DRUG; VEMURAFENIB; 4-AMINO-5-FLUORO-3-(5-(4-METHYLPIPERAZIN-1-YL)-1H-BENZIMIDAZOL-2-YL)QUINOLIN-2(1H)-ONE; BENZIMIDAZOLE DERIVATIVE; INDOLE DERIVATIVE; MOLECULAR LIBRARY; PROTEIN KINASE INHIBITOR; QUINOLONE DERIVATIVE; SULFONAMIDE; TUMOR PROTEIN;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER INHIBITION; CANCER RESISTANCE; CELL CYCLE ARREST; CLONOGENESIS; COLORECTAL CARCINOMA; CROSS RESISTANCE; DRUG EFFICACY; DRUG TARGETING; HUMAN; MELANOMA CELL LINE; METASTATIC MELANOMA; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; TEA; ANIMAL; CELL PROLIFERATION; DRUG EFFECTS; DRUG POTENTIATION; DRUG RESISTANCE; ENZYMOLOGY; GENETICS; MALE; MELANOMA; METABOLISM; MOLECULAR LIBRARY; MUTATION; NUDE MOUSE; PATHOLOGY; PHARMACOLOGY; SIGNAL TRANSDUCTION; TUMOR CELL LINE;

ANIMALS; BENZIMIDAZOLES; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; HUMANS; INDOLES; MALE; MELANOMA; MICE, NUDE; MUTATION; NEOPLASM PROTEINS; PROTEIN KINASE INHIBITORS; QUINOLONES; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES; SULFONAMIDES;

EID: 84931269729     PISSN: 17551471     EISSN: 1755148X     Source Type: Journal    
DOI: 10.1111/pcmr.12376     Document Type: Article

References (53)

1. Abel, E.V., Basile, K.J., Kugel, C.H. 3rd et al. (2013). Melanoma adapts to RAF/MEK inhibitors through FOXD3-mediated upregulation of ERBB3. J. Clin. Investig. 123, 2155-2168.
2. Acquaviva, J., Smith, D.L., Jimenez, J.P., Zhang, C., Sequeira, M., He, S., Sang, J., Bates, R.C., and Proia, D.A. (2014). Overcoming acquired BRAF inhibitor resistance in melanoma via targeted inhibition of Hsp90 with ganetespib. Mol. Cancer Ther. 13, 353-363.
3. Atefi, M., Von Euw, E., Attar, N. et al. (2011). Reversing melanoma cross-resistance to BRAF and MEK inhibitors by co-targeting the AKT/mTOR pathway. PLoS ONE 6, e28973.
4. Becker, D., Meier, C.B., and Herlyn, M. (1989). Proliferation of human malignant melanomas is inhibited by antisense oligodeoxynucleotides targeted against basic fibroblast growth factor. EMBO J. 8, 3685-3691.
5. Becker, D., Lee, P.L., Rodeck, U., and Herlyn, M. (1992). Inhibition of the fibroblast growth factor receptor 1 (FGFR-1) gene in human melanocytes and malignant melanomas leads to inhibition of proliferation and signs indicative of differentiation. Oncogene 7, 2303-2313.
6. Borisy, A.A., Elliott, P.J., Hurst, N.W. et al. (2003). Systematic discovery of multicomponent therapeutics. Proc. Natl Acad. Sci. USA 100, 7977-7982.
7. Bucheit, A.D., and Davies, M.A. (2014). Emerging insights into resistance to BRAF inhibitors in melanoma. Biochem. Pharmacol. 87, 381-389.
8. Chandarlapaty, S., Sawai, A., Scaltriti, M., Rodrik-Outmezguine, V., Grbovic-Huezo, O., Serra, V., Majumder, P.K., Baselga, J., and Rosen, N. (2011). AKT inhibition relieves feedback suppression of receptor tyrosine kinase expression and activity. Cancer Cell 19, 58-71.
9. Chapman, P.B., Hauschild, A., Robert, C. et al. (2011). Improved survival with vemurafenib in melanoma with BRAF V600E mutation. N. Engl. J. Med. 364, 2507-2516.
10. Corcoran, R.B., Ebi, H., Turke, A.B. et al. (2012). EGFR-mediated re-activation of MAPK signaling contributes to insensitivity of BRAF mutant colorectal cancers to RAF inhibition with vemurafenib. Cancer Discov. 2, 227-235.
11. Davis, M.I., Hunt, J.P., Herrgard, S., Ciceri, P., Wodicka, L.M., Pallares, G., Hocker, M., Treiber, D.K., and Zarrinkar, P.P. (2011). Comprehensive analysis of kinase inhibitor selectivity. Nat. Biotechnol. 29, 1046-1051.
12. Easty, D.J., Gray, S.G., O'byrne, K.J., O'donnell, D., and Bennett, D.C. (2011). Receptor tyrosine kinases and their activation in melanoma. Pigment Cell Melanoma Res. 24, 446-461.
13. Eggermont, A.M., Spatz, A., and Robert, C. (2014). Cutaneous melanoma. Lancet 383, 816-827.
14. Escudier, B., Grunwald, V., Ravaud, A. et al. (2014). Phase II results of Dovitinib (TKI258) in patients with metastatic renal cell cancer. Clin. Cancer Res. 20, 3012-3022.
15. Flaherty, K.T., and Fisher, D.E. (2011). New strategies in metastatic melanoma: oncogene-defined taxonomy leads to therapeutic advances. Clin. Cancer Res. 17, 4922-4928.
16. Flaherty, K.T., Infante, J.R., Daud, A. et al. (2012). Combined BRAF and MEK inhibition in melanoma with BRAF V600 mutations. N. Engl. J. Med. 367, 1694-1703.
17. Girotti, M.R., Pedersen, M., Sanchez-Laorden, B. et al. (2013). Inhibiting EGF receptor or SRC family kinase signaling overcomes BRAF inhibitor resistance in melanoma. Cancer Discov. 3, 158-167.
18. Halaban, R., Ghosh, S., and Baird, A. (1987). bFGF is the putative natural growth factor for human melanocytes. In Vitro Cell. Dev. Biol. 23, 47-52.
19. Held, M.A., Langdon, C.G., Platt, J.T. et al. (2013). Genotype-selective combination therapies for melanoma identified by high-throughput drug screening. Cancer Discov. 3, 52-67.
20. Kang, Y.K., Yoo, C., Ryoo, B.Y. et al. (2013). Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib. Br. J. Cancer 109, 2309-2315.
21. Kim, K.B., Chesney, J., Robinson, D., Gardner, H., Shi, M.M., and Kirkwood, J.M. (2011). Phase I/II and pharmacodynamic study of dovitinib (TKI258), an inhibitor of fibroblast growth factor receptors and VEGF receptors, in patients with advanced melanoma. Clin. Cancer Res. 17, 7451-7461.
22. Kugel, C.H. 3rd, and Aplin, A.E. (2014). Adaptive resistance to RAF inhibitors in melanoma. Pigment Cell Melanoma Res. 27, 1032-1038.
23. Lassen, A., Atefi, M., Robert, L., Wong, D.J., Cerniglia, M., Comin-Anduix, B., and Ribas, A. (2014). Effects of AKT inhibitor therapy in response and resistance to BRAF inhibition in melanoma. Mol. Cancer. 13, 83.
24. Lito, P., Pratilas, C.A., Joseph, E.W. et al. (2012). Relief of profound feedback inhibition of mitogenic signaling by RAF inhibitors attenuates their activity in BRAFV600E melanomas. Cancer Cell 22, 668-682.
25. Long, G.V., Fung, C., Menzies, A.M. et al. (2014). Increased MAPK reactivation in early resistance to dabrafenib/trametinib combination therapy of BRAF-mutant metastatic melanoma. Nat. Commun. 5, 5694.
26. Metzner, T., Bedeir, A., Held, G. et al. (2011). Fibroblast growth factor receptors as therapeutic targets in human melanoma: synergism with BRAF inhibition. J. Invest. Dermatol. 131, 2087-2095.
27. Milowsky, M.I., Dittrich, C., Duran, I. et al. (2014). Phase 2 trial of dovitinib in patients with progressive FGFR3-mutated or FGFR3 wild-type advanced urothelial carcinoma. Eur. J. Cancer, 50, 3145-3152.
28. Motzer, R.J., Porta, C., Vogelzang, N.J. et al. (2014). Dovitinib versus sorafenib for third-line targeted treatment of patients with metastatic renal cell carcinoma: an open-label, randomised phase 3 trial. Lancet Oncol. 15, 286-296.
29. Muller, J., Krijgsman, O., Tsoi, J. et al. (2014). Low MITF/AXL ratio predicts early resistance to multiple targeted drugs in melanoma. Nat. Commun. 5, 5712.
30. Nazarian, R., Shi, H., Wang, Q. et al. (2010). Melanomas acquire resistance to B-RAF(V600E) inhibition by RTK or N-RAS upregulation. Nature 468, 973-977.
31. Nesbit, M., Nesbit, H.K., Bennett, J., Andl, T., Hsu, M.Y., Dejesus, E., Mcbrian, M., Gupta, A.R., Eck, S.L., and Herlyn, M. (1999). Basic fibroblast growth factor induces a transformed phenotype in normal human melanocytes. Oncogene 18, 6469-6476.
32. Nihal, M., Ahmad, N., Mukhtar, H., and Wood, G.S. (2005). Anti-proliferative and proapoptotic effects of (-)-epigallocatechin-3-gallate on human melanoma: possible implications for the chemoprevention of melanoma. Int. J. Cancer 114, 513-521.
33. Prahallad, A., Sun, C., Huang, S., Di Nicolantonio, F., Salazar, R., Zecchin, D., Beijersbergen, R.L., Bardelli, A., and Bernards, R. (2012). Unresponsiveness of colon cancer to BRAF(V600E) inhibition through feedback activation of EGFR. Nature 483, 100-103.
34. Rebecca, V.W., Wood, E., Fedorenko, I.V. et al. (2014). Evaluating melanoma drug response and therapeutic escape with quantitative proteomics. Mol. Cell Proteomics 13, 1844-1854.
35. Roller, D.G., Axelrod, M., Capaldo, B.J., Jensen, K., Mackey, A., Weber, M.J., and Gioeli, D. (2012). Synthetic lethal screening with small-molecule inhibitors provides a pathway to rational combination therapies for melanoma. Mol. Cancer Ther. 11, 2505-2515.
36. Sabbatino, F., Wang, Y., Wang, X. et al. (2014). PDGFRalpha up-regulation mediated by sonic hedgehog pathway activation leads to BRAF inhibitor resistance in melanoma cells with BRAF mutation. Oncotarget 5, 1926-1941.
37. Sarker, D., Molife, R., Evans, T.R. et al. (2008). A phase I pharmacokinetic and pharmacodynamic study of TKI258, an oral, multitargeted receptor tyrosine kinase inhibitor in patients with advanced solid tumors. Clin. Cancer Res. 14, 2075-2081.
38. Schlegel, J., Sambade, M.J., Sather, S. et al. (2013). MERTK receptor tyrosine kinase is a therapeutic target in melanoma. J. Clin. Investig. 123, 2257-2267.
39. Shi, H., Kong, X., Ribas, A., and Lo, R.S. (2011). Combinatorial treatments that overcome PDGFRbeta-driven resistance of melanoma cells to V600EB-RAF inhibition. Cancer Res. 71, 5067-5074.
40. Shi, H., Moriceau, G., Kong, X. et al. (2012). Preexisting MEK1 exon 3 mutations in V600E/KBRAF melanomas do not confer resistance to BRAF inhibitors. Cancer Discov. 2, 414-424.
41. Sivanand, S., Pena-Llopis, S., Zhao, H. et al. (2012). A validated tumorgraft model reveals activity of dovitinib against renal cell carcinoma. Sci. Transl. Med. 4, 137ra75.
42. Straussman, R., Morikawa, T., Shee, K. et al. (2012). Tumour micro-environment elicits innate resistance to RAF inhibitors through HGF secretion. Nature 487, 500-504.
43. Sun, C., Wang, L., Huang, S. et al. (2014). Reversible and adaptive resistance to BRAF(V600E) inhibition in melanoma. Nature 508, 118-122.
44. Thumar, J., Shahbazian, D., Aziz, S.A., Jilaveanu, L.B., and Kluger, H.M. (2014). MEK targeting in N-RAS mutated metastatic melanoma. Mol. Cancer. 13, 45.
45. Trudel, S., Li, Z.H., Wei, E., Wiesmann, M., Chang, H., Chen, C., Reece, D., Heise, C., and Stewart, A.K. (2005). CHIR-258, a novel, multitargeted tyrosine kinase inhibitor for the potential treatment of t(4;14) multiple myeloma. Blood 105, 2941-2948.
46. Tworkoski, K., Singhal, G., Szpakowski, S., Zito, C.I., Bacchiocchi, A., Muthusamy, V., Bosenberg, M., Krauthammer, M., Halaban, R., and Stern, D.F. (2011). Phosphoproteomic screen identifies potential therapeutic targets in melanoma. Mol. Cancer Res. 9, 801-812.
47. Wagle, N., Van Allen, E.M., Treacy, D.J. et al. (2014). MAP kinase pathway alterations in BRAF-mutant melanoma patients with acquired resistance to combined RAF/MEK inhibition. Cancer Discov. 4, 61-68.
48. Wang, Y., and Becker, D. (1997). Antisense targeting of basic fibroblast growth factor and fibroblast growth factor receptor-1 in human melanomas blocks intratumoral angiogenesis and tumor growth. Nat. Med. 3, 887-893.
49. Wilson, T.R., Fridlyand, J., Yan, Y. et al. (2012). Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors. Nature 487, 505-509.
50. Yadav, V., Zhang, X., Liu, J., Estrem, S., Li, S., Gong, X.Q., Buchanan, S., Henry, J.R., Starling, J.J., and Peng, S.B. (2012). Reactivation of mitogen-activated protein kinase (MAPK) pathway by FGF receptor 3 (FGFR3)/Ras mediates resistance to vemurafenib in human B-RAF V600E mutant melanoma. J. Biol. Chem. 287, 28087-28098.
51. Zhang, K., Wong, P., Duan, J., Jacobs, B., Borden, E.C., and Bedogni, B. (2013). An ERBB3/ERBB2 oncogenic unit plays a key role in NRG1 signaling and melanoma cell growth and survival. Pigment Cell Melanoma Res. 26, 408-414.
52. Zhu, Z., Aref, A.R., Cohoon, T.J. et al. (2014). Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. Cancer Discov. 4, 452-465.
53. Zipser, M.C., Eichhoff, O.M., Widmer, D.S. et al. (2011). A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status. Pigment Cell Melanoma Res. 24, 326-333.