Biomarkers and novel therapeutic targets in gastrointestinal stromal tumors (GISTs)

Recent Patents on Anti-Cancer Drug Discovery

Volumn 8, Issue 3, 2013, Pages 288-297

  Campanella, Nathália C ^a   de Oliveira, António T ^a   Scapulatempo Neto, Cristovam ^a   Guimarães, Denise P ^a   Reis, Rui M ^a,b  

^a BARRETOS CANCER HOSPITAL   (Brazil)

^b UNIVERSITY OF MINHO   (Portugal)

Author keywords

Gastrointestinal stromal tumor; Imatinib; KIT; New patents; PDGFRA; Sunitinib

Indexed keywords

AT 13387; CRENOLANIB; CYCLIC AMP DEPENDENT PROTEIN KINASE; DASATINIB; DOVITINIB; FOCAL ADHESION KINASE; GANETESPIB; GELDANAMYCIN; HEAT SHOCK PROTEIN 90 INHIBITOR; HYPOXIA INDUCIBLE FACTOR 1ALPHA; IMATINIB; LINSITINIB; MASITINIB; MICRORNA; MICRORNA 494; MITOGEN ACTIVATED PROTEIN KINASE; NEVAXAR; NILOTINIB; PAZOPANIB; PHOSPHATIDYLINOSITIDE; PLATELET DERIVED GROWTH FACTOR RECEPTOR; PROTEIN KINASE B; REGORAFENIB; SOMATOMEDIN B; SORAFENIB; STAT PROTEIN; STEM CELL FACTOR RECEPTOR; SUCCINATE DEHYDROGENASE; SUNITINIB; UNCLASSIFIED DRUG; UNINDEXED DRUG; VASCULOTROPIN; VATALANIB; WO 2011117568;

APOPTOSIS; ARTICLE; AUTOPHOSPHORYLATION; CANCER PROGNOSIS; CARCINOGENESIS; CELL ADHESION; CELL DIFFERENTIATION; CELL PROLIFERATION; CELL SURVIVAL; DIARRHEA; DRUG DOSE INCREASE; FATIGUE; GASTROINTESTINAL STROMAL TUMOR; GENE EXPRESSION; GENE MUTATION; HUMAN; IMMUNOHISTOCHEMISTRY; IMMUNOREACTIVITY; MITOSIS INDEX; MULTICENTER STUDY (TOPIC); NAUSEA AND VOMITING; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; TUMOR VOLUME;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DESIGN; GASTROINTESTINAL STROMAL TUMORS; GENE EXPRESSION REGULATION, NEOPLASTIC; GENETIC PREDISPOSITION TO DISEASE; GENETIC TESTING; HUMANS; MOLECULAR TARGETED THERAPY; PATENTS AS TOPIC; PREDICTIVE VALUE OF TESTS; SIGNAL TRANSDUCTION; TUMOR MARKERS, BIOLOGICAL;

EID: 84888039222     PISSN: 15748928     EISSN: None     Source Type: Journal    
DOI: 10.2174/15748928113089990030     Document Type: Article

References (101)

1. Corless CL, Barnett CM, Heinrich MC. Gastrointestinal stromal tumours: Origin and molecular oncology. Nat Rev Cancer 2011; 11(12): 865-78.
2. Yang J, Du X, Lazar AJ, Pollock R, Hunt K, Chen K, et al. Genetic aberrations of gastrointestinal stromal tumors. Cancer 2008; 113(7): 1532-43.
3. Gomes AL, Gouveia A, Capelinha AF, de la Cruz D, Silva P, Reis RM, et al. Molecular alterations of KIT and PDGFRA in GISTs: Evaluation of a Portuguese series. J Clin Pathol 2008; 61(2): 203-8.
4. Fukasawa T, Chong JM, Sakurai S, Koshiishi N, Ikeno R, Tanaka A, et al. Allelic loss of 14q and 22q, NF2 mutation, and genetic instability occur independently of c-kit mutation in gastrointestinal stromal tumor. Jpn J Cancer Res 2000; 91(12): 1241-9.
5. Kikuta K, Kubota D, Saito T, Orita H, Yoshida A, Tsuda H, et al. Clinical proteomics identified ATP-dependent RNA helicase DDX39 as a novel biomarker to predict poor prognosis of patients with gastrointestinal stromal tumor. J Proteomics 2012; 75(4): 1089-98.
6. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: Recurrence patterns and prognostic factors for survival. Ann Surg 2000; 231(1): 51-8.
7. Miranda ME, Alberti LR, Tatsuo ES, Picarro C, Rausch M. Gastrointestinal stromal tumor of the stomach in a child with a 3-year follow-up period-case report. Int J Surg Case Rep 2011; 2(6): 114-7.
8. Stamatakos M, Douzinas E, Stefanaki C, Safioleas P, Polyzou E, Levidou G, et al. Gastrointestinal stromal tumor. World J Surg Oncol 2009; 7: 61.
9. Stewart DR, Corless CL, Rubin BP, Heinrich MC, Messiaen LM, Kessler LJ, et al. Mitotic recombination as evidence of alternative pathogenesis of gastrointestinal stromal tumours in neurofibromatosis type 1. J Med Genet 2007; 44(1): e61.
10. de Oliveira AT, Reis RM, Afonso J, Martinho O, Matos D, Carvalho AL, et al. Lymphangiogenic VEGF-C and VEGFR-3 expression in genetically characterised gastrointestinal stromal tumours. Histol Histopathol 2011; 26(12): 1499-507.
11. Fregnani JH, de Oliveira AT, de Lima Vazquez V, Viana CR, Longatto-Filho A, Reis RM. Is the gastrointestinal stromal tumor arising in the rectovaginal septum an extragastrointestinal entity? A time for reflection. Int J Colorectal Dis 2011; 26(3): 387-9.
12. Lam MM, Corless CL, Goldblum JR, Heinrich MC, Downs-Kelly E, Rubin BP. Extragastrointestinal stromal tumors presenting as vulvovaginal/rectovaginal septal masses: A diagnostic pitfall. Int J Gynecol Pathol 2006; 25(3): 288-92.
13. Corless CL, Heinrich MC. Molecular pathobiology of gastrointestinal stromal sarcomas. Annu Rev Pathol 2008; 3: 557-86.
14. Gasparotto D, Rossi S, Bearzi I, Doglioni C, Marzotto A, Hornick JL, et al. Multiple primary sporadic gastrointestinal stromal tumors in the adult: An underestimated entity. Clin Cancer Res 2008; 14(18): 5715-21.
15. Bosoteanu M, Bosoteanu C, Deacu M, Aschie M. Differential diagnosis of a gastric stromal tumor: Case report and literature review. Rom J Morphol Embryol 2011; 52(4): 1361-8.
16. Patil DT, Rubin BP. Gastrointestinal stromal tumor: Advances in diagnosis and management. Arch Pathol Lab Med 2011; 135(10): 1298-310.
17. Cassier PA, Ducimetiere F, Lurkin A, Ranchere-Vince D, Scoazec JY, Bringuier PP, et al. A prospective epidemiological study of new incident GISTs during two consecutive years in Rhone Alpes region: Incidence and molecular distribution of GIST in a European region. Br J Cancer 2010; 103(2): 165-70.
18. Emile JF, Brahimi S, Coindre JM, Bringuier PP, Monges G, Samb P, et al. Frequencies of KIT and PDGFRA mutations in the MolecGIST prospective population-based study differ from those of advanced GISTs. Med Oncol 2012; 29(3): 1765-72.
19. Fletcher CD, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, et al. Diagnosis of gastrointestinal stromal tumors: A consensus approach. Int J Surg Pathol 2002; 10(2): 81-9.
20. Miettinen M, Sobin LH, Lasota J. Gastrointestinal stromal tumors of the stomach: A clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. Am J Surg Pathol 2005; 29(1): 52-68.
21. Miettinen M, Lasota J. Gastrointestinal stromal tumors: Pathology and prognosis at different sites. Semin Diagn Pathol 2006; 23(2): 70-83.
22. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998; 279(5350): 577-80.
23. Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM. Gastrointestinal pacemaker cell tumor (GIPACT): Gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 1998; 152(5): 1259-69.
24. Tan CB, Zhi W, Shahzad G, Mustacchia P. Gastrointestinal stromal tumors: A review of case reports, diagnosis, treatment, and future directions. ISRN Gastroenterol 2012; 2012: 595968.
25. Antonescu CR. The GIST paradigm: Lessons for other kinasedriven cancers. J Pathol 2011; 223(2): 251-61.
26. Sabah M, Cummins R, Leader M, Kay E. Loss of heterozygosity of chromosome 9p and loss of p16INK4A expression are associated with malignant gastrointestinal stromal tumors. Mod Pathol 2004; 17(11): 1364-71.
27. Martinho O, Gouveia A, Viana-Pereira M, Silva P, Pimenta A, Reis RM, et al. Low frequency of MAP kinase pathway alterations in KIT and PDGFRA wild-type GISTs. Histopathology 2009; 55(1): 53-62.
28. Duensing A, Medeiros F, McConarty B, Joseph NE, Panigrahy D, Singer S, et al. Mechanisms of oncogenic KIT signal transduction in primary gastrointestinal stromal tumors (GISTs). Oncogene 2004; 23(22): 3999-4006.
29. Mol CD, Dougan DR, Schneider TR, Skene RJ, Kraus ML, Scheibe DN, et al. Structural basis for the autoinhibition and STI-571 inhibition of c-Kit tyrosine kinase. J Biol Chem 2004; 279(30): 31655-63.
30. Blay JY. Pharmacological management of gastrointestinal stromal tumours: An update on the role of sunitinib. Ann Oncol 2010; 21(2): 208-15.
31. Blackstein ME, Blay JY, Corless C, Driman DK, Riddell R, Soulieres D, et al. Gastrointestinal stromal tumours: Consensus statement on diagnosis and treatment. Can J Gastroenterol 2006; 20(3): 157-63.
32. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004; 22(18): 3813-25.
33. Braggio E, Braggio DA, Small IA, Lopes LF, Valadao M, Gouveia ME, et al. Prognostic relevance of KIT and PDGFRA mutations in gastrointestinal stromal tumors. Anticancer Res 2010; 30(6): 2407-14.
34. Antonescu CR, Viale A, Sarran L, Tschernyavsky SJ, Gonen M, Segal NH, et al. Gene expression in gastrointestinal stromal tumors is distinguished by KIT genotype and anatomic site. Clin Cancer Res 2004; 10(10): 3282-90.
35. Belinsky MG, Skorobogatko YV, Rink L, Pei J, Cai KQ, Vanderveer LA, et al. High density DNA array analysis reveals distinct genomic profiles in a subset of gastrointestinal stromal tumors. Genes Chromosomes Cancer 2009; 48(10): 886-96.
36. Agaram NP, Wong GC, Guo T, Maki RG, Singer S, Dematteo RP, et al. Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors. Genes Chromosomes Cancer 2008; 47(10): 853-9.
37. Agaimy A, Terracciano LM, Dirnhofer S, Tornillo L, Foerster A, Hartmann A, et al. V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J Clin Pathol 2009; 62(7): 613-6.
38. Hostein I, Faur N, Primois C, Boury F, Denard J, Emile JF, et al. BRAF mutation status in gastrointestinal stromal tumors. Am J Clin Pathol 2010; 133(1): 141-8.
39. Janeway KA, Kim SY, Lodish M, Nose V, Rustin P, Gaal J, et al. Defects in succinate dehydrogenase in gastrointestinal stromal tumors lacking KIT and PDGFRA mutations. Proc Natl Acad Sci USA 2011; 108(1): 314-8.
40. Neves LR, Oshima CT, Artigiani-Neto R, Yanaguibashi G, Lourenco LG, Forones NM. Ki67 and p53 in gastrointestinal stromal tumors--GIST. Arq Gastroenterol 2009; 46(2): 116-20.
41. Pantaleo MA, Astolfi A, Indio V, Moore R, Thiessen N, Heinrich MC, et al. SDHA loss-of-function mutations in KIT-PDGFRA wild-type gastrointestinal stromal tumors identified by massively parallel sequencing. J Natl Cancer Inst 2011; 103(12): 983-7.
42. de Oliveira AT, Pinheiro C, Longatto-Filho A, Brito MJ, Martinho O, Matos D, et al. Co-expression of monocarboxylate transporter 1 (MCT1) and its chaperone (CD147) is associated with low survival in patients with gastrointestinal stromal tumors (GISTs). J Bioenerg Biomembr 2012; 44(1): 171-8.
43. Chou A, Chen J, Clarkson A, Samra JS, Clifton-Bligh RJ, Hugh TJ, et al. Succinate dehydrogenase-deficient GISTs are characterized by IGF1R overexpression. Mod Pathol 2012; 25(9): 1307-13.
44. Pasini B, McWhinney SR, Bei T, Matyakhina L, Stergiopoulos S, Muchow M, et al. Clinical and molecular genetics of patients with the Carney-Stratakis syndrome and germline mutations of the genes coding for the succinate dehydrogenase subunits SDHB, SDHC, and SDHD. Eur J Hum Genet 2008; 16(1): 79-88.
45. Linehan WM, Srinivasan R, Schmidt LS. The genetic basis of kidney cancer: A metabolic disease. Nat Rev Urol 2010; 7(5): 277-85.
46. Ricketts C, Woodward ER, Killick P, Morris MR, Astuti D, Latif F, et al. Germline SDHB mutations and familial renal cell carcinoma. J Natl Cancer Inst 2008; 100(17): 1260-2.
47. Tarn C, Rink L, Merkel E, Flieder D, Pathak H, Koumbi D, et al. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci USA 2008; 105(24): 8387-92.
48. Janeway KA, Zhu MJ, Barretina J, Perez-Atayde A, Demetri GD, Fletcher JA. Strong expression of IGF1R in pediatric gastrointestinal stromal tumors without IGF1R genomic amplification. Int J Cancer 2010; 127(11): 2718-22.
49. Zong L, Chen P, Jiang J, Wang H, Wang L. Correlation between p16 expression and malignant risk of gastrointestinal stromal tumor: Evidence from nine studies. Hepatogastroenterology 2012; 59(117): 1458-63.
50. Lagarde P, Perot G, Kauffmann A, Brulard C, Dapremont V, Hostein I, et al. Mitotic checkpoints and chromosome instability are strong predictors of clinical outcome in gastrointestinal stromal tumors. Clin Cancer Res 2012; 18(3): 826-38.
51. Haller F, Gunawan B, von Heydebreck A, Schwager S, Schulten HJ, Wolf-Salgo J, et al. Prognostic role of E2F1 and members of the CDKN2A network in gastrointestinal stromal tumors. Clin Cancer Res 2005; 11(18): 6589-97.
52. Wozniak A, Sciot R, Guillou L, Pauwels P, Wasag B, Stul M, et al. Array CGH analysis in primary gastrointestinal stromal tumors: Cytogenetic profile correlates with anatomic site and tumor aggressiveness, irrespective of mutational status. Genes Chromosomes Cancer 2007; 46(3): 261-76.
53. Chen Y, Tzeng CC, Liou CP, Chang MY, Li CF, Lin CN. Biological significance of chromosomal imbalance aberrations in gastrointestinal stromal tumors. J Biomed Sci 2004; 11(1): 65-71.
54. Heinrich MC, Rubin BP, Longley BJ, Fletcher JA. Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 2002; 33(5): 484-95.
55. Kim WK, Park M, Kim YK, Tae YK, Yang HK, Lee JM, et al. MicroRNA-494 downregulates KIT and inhibits gastrointestinal stromal tumor cell proliferation. Clin Cancer Res 2011; 17(24): 7584-94.
56. Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: A sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 1998; 11(8): 728-34.
57. Perez D, Demartines N, Meier K, Clavien PA, Jungbluth A, Jaeger D. Protein S100 as prognostic marker for gastrointestinal stromal tumors: A clinicopathological risk factor analysis. J Invest Surg 2007; 20(3): 181-6.
58. West RB, Corless CL, Chen X, Rubin BP, Subramanian S, Montgomery K, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004; 165(1): 107-13.
59. Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors: A study of 1840 cases. Am J Surg Pathol 2009; 33(9): 1401-8.
60. Espinosa I, Lee CH, Kim MK, Rouse BT, Subramanian S, Montgomery K, et al. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol 2008; 32(2): 210-8.
61. Lopes LF, West RB, Bacchi LM, van de Rijn M, Bacchi CE. DOG1 for the diagnosis of gastrointestinal stromal tumor (GIST): Comparison between 2 different antibodies. Appl Immunohistochem Mol Morphol 2010; 18(4): 333-7.
62. Tornillo L, Terracciano LM. An update on molecular genetics of gastrointestinal stromal tumours. J Clin Pathol 2006; 59(6): 557-63.
63. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003; 21(23): 4342-9.
64. Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, et al. PDGFRA mutations in gastrointestinal stromal tumors: Frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005; 23(23): 5357-64.
65. Niinuma T, Suzuki H, Nojima M, Nosho K, Yamamoto H, Takamaru H, et al. Upregulation of miR-196a and HOTAIR drive malignant character in gastrointestinal stromal tumors. Cancer Res 2012; 72(5): 1126-36.
66. Yeh CN, Chen YY, Tseng JH, Chen JS, Chen TW, Tsai CY, et al. Imatinib mesylate for patients with recurrent or metastatic gastrointestinal stromal tumors expressing KIT: A decade experience from Taiwan. Transl Oncol 2011; 4(6): 328-35.
67. Lopes LF, Bacchi CE. Imatinib treatment for gastrointestinal stromal tumour (GIST). J Cell Mol Med 2010; 14(1-2): 42-50.
68. Heinrich MC, Marino-Enriquez A, Presnell A, Donsky RS, Griffith DJ, McKinley A, et al. Sorafenib inhibits many kinase mutations associated with drug-resistant gastrointestinal stromal tumors. Mol Cancer Ther 2012; 11(8): 1770-80.
69. Joensuu H, De Braud F, Grignagni G, De Pas T, Spitalieri G, Coco P, et al. Vatalanib for metastatic gastrointestinal stromal tumour (GIST) resistant to imatinib: Final results of a phase II study. Br J Cancer 2011; 104(11): 1686-90.
70. Sugiyama M, Fujita K, Murayama N, Akiyama Y, Yamazaki H, Sasaki Y. Sorafenib and sunitinib, two anticancer drugs, inhibit CYP3A4-mediated and activate CY3A5-mediated midazolam 1'-hydroxylation. Drug Metab Dispos 2011; 39(5): 757-62.
71. Rutkowski P, Bylina E, Klimczak A, Switaj T, Falkowski S, Kroc J, et al. The outcome and predictive factors of sunitinib therapy in advanced gastrointestinal stromal tumors (GIST) after imatinib failure-one institution study. BMC Cancer 2012; 12: 107.
72. Svetlichnaya J, Huyck TK, Wayne JD, Agulnik M. Neoadjuvant use of sunitinib in locally advanced GIST with intolerance to imatinib. Chemotherapy 2012; 58(1): 30-3.
73. Cauchi C, Somaiah N, Engstrom PF, Litwin S, Lopez M, Lee J, et al. Evaluation of nilotinib in advanced GIST previously treated with imatinib and sunitinib. Cancer Chemother Pharmacol 2012; 69(4): 977-82.
74. Dizdar O, Yalcin S. Nilotinib in advanced gastrointestinal stromal tumors after imatinib and sunitinib therapy. Hepatogastroenterology 2011; 58(112): 2012-4.
75. Joensuu H. Risk stratification of patients diagnosed with gastrointestinal stromal tumor. Hum Pathol 2008; 39(10): 1411-9.
76. Moussy, A. J. Trearment of GIST with Masitinib. US20120302577 (2012) & WO2011092273 (2011).
77. Dubreuil P, Letard S, Ciufolini M, Gros L, Humbert M, Casteran N, et al. Masitinib (AB1010), a potent and selective tyrosine kinase inhibitor targeting KIT. PLoS One 2009; 4(9): e7258.
78. Siesser PM, Hanks SK. The signaling and biological implications of FAK overexpression in cancer. Clin Cancer Res 2006; 12(11 Pt 1): 3233-7.
79. Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, et al. Long-term results from a randomized phase II trial of standard-versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 2008; 26(4): 620-5.
80. Science A. A phase 3 study to evaluate efficacy and safety of masitinib in comparison to imatinib in patients with gastrointestinal stromal tumour in first line medical treatment. NCT00812240 (2012).
81. Cheeseman, M. T., Brown, S. D. M. Compounds targeting the vegf and/or hif pathway such as sorafenib or vatalanib for use in the treatment of otitis media. WO2011117568 (2011).
82. Soria JC, Massard C, Magne N, Bader T, Mansfield CD, Blay JY, et al. Phase 1 dose-escalation study of oral tyrosine kinase inhibitor masitinib in advanced and/or metastatic solid cancers. Eur J Cancer 2009; 45(13): 2333-41.
83. Carty, S., Jenkins, S., Liversidge, G. Nanoparticulate sorafenib formulations. EP2049084 (2009), US20080213374 (2008) & WO2008008733 (2008).
84. Shah NP, Lee FY, Luo R, Jiang Y, Donker M, Akin C. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood 2006; 108(1): 286-91.
85. Schittenhelm MM, Shiraga S, Schroeder A, Corbin AS, Griffith D, Lee FY, et al. Dasatinib (BMS-354825), a dual SRC/ABL kinase inhibitor, inhibits the kinase activity of wild-type, juxtamembrane, and activation loop mutant KIT isoforms associated with human malignancies. Cancer Res 2006; 66(1): 473-81.
86. Clinical trials. Available at: http://www. clinicaltrials. gov/ct2/search. (Accessed on: August 1, 2012).
87. Lewis NL, Lewis LD, Eder JP, Reddy NJ, Guo F, Pierce KJ, et al. Phase I study of the safety, tolerability, and pharmacokinetics of oral CP-868, 596, a highly specific platelet-derived growth factor receptor tyrosine kinase inhibitor in patients with advanced cancers. J Clin Oncol 2009; 27(31): 5262-9.
88. Michael M, Vlahovic G, Khamly K, Pierce KJ, Guo F, Olszanski AJ. Phase Ib study of CP-868, 596, a PDGFR inhibitor, combined with docetaxel with or without axitinib, a VEGFR inhibitor. Br J Cancer 2010; 103(10): 1554-61.
89. LLC AP. Phase II study of crenolanib (CP-868, 596), for the treatment of patients with advanced gastrointestinal stromal tumors with the D842-related mutations and deletions in the PDGFRA gene. NCT01243346 (2012).
90. Podar K, Tonon G, Sattler M, Tai YT, Legouill S, Yasui H, et al. The small-molecule VEGF receptor inhibitor pazopanib (GW786034B) targets both tumor and endothelial cells in multiple myeloma. Proc Natl Acad Sci USA 2006; 103(51): 19478-83.
91. Berard CL. Efficacy of pazopanib in gastrointestinal stromal tumors (GIST) (PAZOGIST). NCT01323400 (2012).
92. Sarker D, Molife R, Evans TR, Hardie M, Marriott C, Butzberger-Zimmerli P, et al. 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 2008; 14(7): 2075-81.
93. Novartis. Efficacy and safety of dovitinib in patients with gastrointestinal stromal tumors refractory and/or intolerant to imatinib (DoviGIST). NCT01478373 (2011).
94. Proia DA, Foley KP, Korbut T, Sang J, Smith D, Bates RC, et al. Multifaceted intervention by the Hsp90 inhibitor ganetespib (STA-9090) in cancer cells with activated JAK/STAT signaling. PLoS One 2011; 6(4): e18552.
95. Wang Y, Trepel JB, Neckers LM, Giaccone G. STA-9090, a smallmolecule Hsp90 inhibitor for the potential treatment of cancer. Curr Opin Investig Drugs 2010; 11(12): 1466-76.
96. Taldone T, Gozman A, Maharaj R, Chiosis G. Targeting Hsp90: Small-molecule inhibitors and their clinical development. Curr Opin Pharmacol 2008; 8(4): 370-4.
97. National Health Research Institutes T. A study of AUY922 for GIST(Gastrointestinal Stromal Tumor) patients. NCT01389583 (2011).
98. Corp. SP. A study evaluating STA-9090 in patients with metastatic and/or unresectable Gastrointestinal Stromal Tumor (GIST). NCT01039519 (2011).
99. Pharmaceuticals A. A study to investigate the safety and efficacy of AT13387, alone or in combination with imatinib, in patients with GIST. NCT01294202 (2012).
100. NCI. Linsitinib in Treating Patients with gastrointestinal stromal tumors. NCT01560260 (2012).
101. Chi, P., Chen, Y., Sawyers, C., Allis, C. D. ETV1 as a diagnostic, prognostic and therapeutic target forgastrointestinal stromal tumors. WO2012034076 (2012).