Combination small molecule MEK and PI3K inhibition enhances uveal melanoma cell death in a mutant GNAQ- and GNA11-dependent manner

Clinical Cancer Research

Volumn 18, Issue 16, 2012, Pages 4345-4355

  Khalili, Jahan S ^a   Yu, Xiaoxing ^a   Wang, Ji ^a   Hayes, Brendan C ^a   Davies, Michael A ^a   Lizee, Gregory ^a   Esmaeli, Bita ^a   Woodman, Scott E ^a  

^a UNIVERSITY OF TEXAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GSK 2126458; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE INHIBITOR; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE INHIBITOR; PROTEIN KINASE B; TRAMETINIB; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CANCER CELL CULTURE; CANCER COMBINATION CHEMOTHERAPY; CANCER GROWTH; CANCER INHIBITION; CELL CYCLE ARREST; CELL CYCLE REGULATION; CELL DEATH; CONCENTRATION RESPONSE; CONTROLLED STUDY; ENZYME INHIBITION; ENZYME PHOSPHORYLATION; GENE; GENE MUTATION; GNA11 GENE; GNAQ GENE; IN VITRO STUDY; INTRACELLULAR SIGNALING; MOLECULAR GENETICS; MONOTHERAPY; PRIORITY JOURNAL; PROTEOMICS; RNA INTERFERENCE; TREATMENT RESPONSE; UVEA MELANOMA;

ANTINEOPLASTIC COMBINED CHEMOTHERAPY PROTOCOLS; APOPTOSIS; CELL CYCLE; CELL DEATH; CELL LINE, TUMOR; CELL PROLIFERATION; DOSE-RESPONSE RELATIONSHIP, DRUG; ENZYME INHIBITORS; GENE SILENCING; GTP-BINDING PROTEIN ALPHA SUBUNITS; HUMANS; MELANOMA; MITOGEN-ACTIVATED PROTEIN KINASE KINASES; MUTATION; PHOSPHATIDYLINOSITOL 3-KINASES; PYRIDONES; PYRIMIDINONES; QUINOLINES; SIGNAL TRANSDUCTION; SULFONAMIDES; UVEAL NEOPLASMS;

EID: 84865096605     PISSN: 10780432     EISSN: 15573265     Source Type: Journal    
DOI: 10.1158/1078-0432.CCR-11-3227     Document Type: Article

References (36)

1. Bedikian AY. Metastatic uveal melanoma therapy: current options. Int Ophthalmol Clin 2006;46:151-66.
2. Kimple AJ, Bosch DE, Giguere PM, Siderovski DP. Regulators of G-protein signaling and their Galpha substrates: promises and challenges in their use as drug discovery targets. Pharmacol Rev 2011;63:728-49.
3. Populo H, Soares P, Rocha AS, Silva P, Lopes JM. Evaluation of the mTOR pathway in ocular (uvea and conjunctiva) melanoma. Melanoma Res 2010;20:107-17.
4. Saraiva VS, Caissie AL, Segal L, Edelstein C, Burnier MN Jr. Immunohistochemical expression of phospho-Akt in uveal melanoma. Melanoma Res 2005;15:245-50.
5. Weber A, Hengge UR, Urbanik D, Markwart A, Mirmohammadsaegh A, Reichel MB, et al. Absence of mutations of the BRAF gene and constitutive activation of extracellular-regulated kinase in malignant melanomas of the uvea. Lab Invest 2003;83:1771-6.
6. Zuidervaart W, van Nieuwpoort F, Stark M, Dijkman R, Packer L, Borgstein AM, et al. Activation of the MAPK pathway is a common event in uveal melanomas although it rarely occurs through mutation of BRAF or RAS. Br J Cancer 2005;92:2032-8.
7. All-Ericsson C, Girnita L, Muller-Brunotte A, Brodin B, Seregard S, Ostman A, et al. c-Kit-dependent growth of uvealmelanomacells: a potential therapeutic target? Invest Ophthalmol Vis Sci 2004;45:2075-82.
8. Cohen Y, Goldenberg-Cohen N, Parrella P, Chowers I, Merbs SL, Pe'er J, et al. Lack of BRAF mutation in primary uveal melanoma. Invest Ophthalmol Vis Sci 2003;44:2876-8.
9. Cruz F 3rd, Rubin BP, Wilson D, Town A, Schroeder A, Haley A, et al. Absence of BRAF and NRAS mutations in uveal melanoma. Cancer Res 2003;63:5761-6.
10. Edmunds SC, Cree IA, Di Nicolantonio F, Hungerford JL, Hurren JS, Kelsell DP. Absence of BRAF gene mutations in uveal melanomas in contrast to cutaneous melanomas. Br J Cancer 2003;88:1403-5.
11. Pache M, Glatz K, Bosch D, Dirnhofer S, Mirlacher M, Simon R, et al. Sequence analysis and high-throughput immunohistochemical profiling of KIT (CD 117) expression in uveal melanoma using tissue microarrays. Virchows Arch 2003;443:741-4.
12. Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, et al. Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature 2009;457:599-602.
13. Van Raamsdonk CD, Griewank KG, Crosby MB, Garrido MC, Vemula S, Wiesner T, et al. Mutations in GNA11 in uveal melanoma. N Engl J Med 2010;363:2191-9.
14. Jiang X, Zhou J, Yuen NK, Corless CL, Heinrich MC, Fletcher JA, et al. Imatinib targeting of KIT-mutant oncoprotein in melanoma. Clin Cancer Res 2008;14:7726-32.
15. Gilmartin AG, Bleam MR, Groy A, Moss KG, Minthorn EA, Kulkarni SG, et al. GSK1120212 (JTP-74057) is an inhibitor of MEK activity and activation with favorable pharmacokinetic properties for sustained in vivo pathway inhibition. Clin Cancer Res 2011;17:989-1000.
16. Infante JR, Fecher LA, Nallapareddy S, Gordon MS, Flaherty KT, Cox DJ, et al. Safety and efficacy results from the first-in-human study of the oral MEK 1/2 inhibitor GSK1120212. J Clin Oncol 2010;28:15S-S.
17. Steven D Knight NDA, Burgess Joelle L, Chaudhari Amita M, Darcy Michael G, Donatelli Carla A, Luengo Juan I, et al. Discovery of GSK2126458, a highly potent inhibitor of PI3K and the mammalian target of rapamycin. ACS Med Chem Lett 2010;1:39-43.
18. Ballou LM, Chattopadhyay M, Li Y, Scarlata S, Lin RZ. Galphaq binds to p110alpha/p85alpha phosphoinositide 3-kinase and displaces Ras. Biochem J 2006;394:557-62.
19. Howes AL, Miyamoto S, Adams JW, Woodcock EA, Brown JH. Galphaq expression activates EGFR and induces Akt mediated cardiomyocyte survival: dissociation from Galphaq mediated hypertrophy. J Mol Cell Cardiol 2006;40:597-604.
20. Hennessy BT, Lu Y, Poradosu E, Yu Q, Yu S, Hall H, et al. Pharmacodynamic markers of perifosine efficacy. Clin Cancer Res 2007;13:7421-31.
21. Tibes R, Qiu Y, Lu Y, Hennessy B, Andreeff M, Mills GB, et al. Reverse phase protein array: validation of a novel proteomic technology and utility for analysis of primary leukemia specimens and hematopoietic stem cells. Mol Cancer Ther 2006;5:2512-21.
22. Lu Y, Muller M, Smith D, Dutta B, Komurov K, Iadevaia S, et al. Kinome siRNA-phosphoproteomic screen identifies networks regulating AKT signaling. Oncogene 2011;30:4567-77.
23. Komurov K, White MA, Ram PT. Use of data-biased random walks on graphs for the retrieval of context-specific networks from genomic data. PLoS Comput Biol 2010;6.
24. Li AP, Colburn SM, Beck DJ. A simplified method for the culturing of primary adult rat and human hepatocytes as multicellular spheroids. In Vitro Cell Dev Biol 1992;28A:673-7.
25. Griewank KG, Yu X, Khalili J, Sozen MM, Stempke-Hale K, Bernatchez C, et al. Genetic and molecular characterization of uveal melanoma cell lines. Pigment Cell Melanoma Res 2012;25:182-7.
26. Smalley KS, Haass NK, Brafford PA, Lioni M, Flaherty KT, Herlyn M. Multiple signaling pathways must be targeted to overcome drug resistance in cell lines derived from melanoma metastases. Mol Cancer Ther 2006;5:1136-44.
27. Janssen CS, Sibbett R, Henriquez FL, McKay IC, Kemp EG, Roberts F. The T1799A point mutation is present in posterior uveal melanoma. Br J Cancer 2008;99:1673-7.
28. Maat W, Kilic E, Luyten GP, de Klein A, Jager MJ, Gruis NA, et al. Pyrophosphorolysis detects B-RAF mutations in primary uveal melanoma. Invest Ophthalmol Vis Sci 2008;49:23-7.
29. Meier F, Schittek B, Busch S, Garbe C, Smalley K, Satyamoorthy K, et al. The RAS/RAF/MEK/ERK and PI3K/AKT signaling pathways present molecular targets for the effective treatment of advanced melanoma. Front Biosci 2005;10:2986-3001.
30. Sos ML, Fischer S, Ullrich R, Peifer M, Heuckmann JM, Koker M, et al. Identifying genotype-dependent efficacy of single and combined PI3K- and MAPK-pathway inhibition in cancer. Proc Natl Acad Sci U S A 2009;106:18351-6.
31. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, et al. 4E-BP1 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.
32. Adjei AA, Cohen RB, Franklin W, Morris C, Wilson D, Molina JR, 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;26:2139-46.
33. Patel M, Smyth E, Chapman PB, Wolchok JD, Schwartz GK, Abramson DH, et al. Therapeutic implications of the emerging molecular biology of uveal melanoma. Clin Cancer Res 2011;17:2087-100.
34. 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.
35. Hoeflich KP, O'Brien C, Boyd Z, Cavet G, Guerrero S, Jung K, et al. In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res 2009;15:4649-64.
36. 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.