Emerging Agents for the Treatment of Advanced, Imatinib-Resistant Gastrointestinal Stromal Tumors: Current Status and Future Directions

Drugs

Volumn 75, Issue 12, 2015, Pages 1323-1334

  Bauer, Sebastian ^a,b   Joensuu, Heikki ^c  

^a UNIVERSITY HOSPITAL ESSEN   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; DOVITINIB; IMATINIB; MASITINIB; PAZOPANIB; PONATINIB; REGORAFENIB; SORAFENIB; SUNITINIB; NEW DRUG; PROTEIN KINASE INHIBITOR; PROTEIN TYROSINE KINASE;

ARTICLE; CANCER CHEMOTHERAPY; CANCER RESISTANCE; CANCER SCREENING; DNA SEQUENCE; GASTROINTESTINAL STROMAL TUMOR; GENE MUTATION; HUMAN; LIVER FUNCTION TEST; OUTCOME ASSESSMENT; OVERALL SURVIVAL; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); RISK ASSESSMENT; SIGNAL TRANSDUCTION; TREATMENT RESISTANT DEPRESSION; ANIMAL; ANTAGONISTS AND INHIBITORS; DRUG DEVELOPMENT; DRUG EFFECTS; DRUG RESISTANCE; ENZYMOLOGY; FORECASTING; GASTROINTESTINAL NEOPLASMS; GASTROINTESTINAL STROMAL TUMORS; GENETICS; METABOLISM; MOLECULARLY TARGETED THERAPY; MUTATION; PATHOLOGY; TREATMENT OUTCOME; TRENDS;

ANIMALS; ANTINEOPLASTIC AGENTS; DRUG DISCOVERY; DRUG RESISTANCE, NEOPLASM; DRUGS, INVESTIGATIONAL; FORECASTING; GASTROINTESTINAL NEOPLASMS; GASTROINTESTINAL STROMAL TUMORS; HUMANS; IMATINIB MESYLATE; MOLECULAR TARGETED THERAPY; MUTATION; PROTEIN KINASE INHIBITORS; PROTEIN-TYROSINE KINASES; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

EID: 84939266999     PISSN: 00126667     EISSN: 11791950     Source Type: Journal    
DOI: 10.1007/s40265-015-0440-8     Document Type: Article

References (100)

1. Ducimetière F, Lurkin A, Ranchère-Vince D, Decouvelaere AV, Péoc'h M, Istier L, et al. Incidence of sarcoma histotypes and molecular subtypes in a prospective epidemiological study with central pathology review and molecular testing. PLoS One. 2011;6(8):e20294.
2. Kawanowa K, Sakuma Y, Sakurai S, Hishima T, Iwasaki Y, Saito K, et al. High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol. 2006;37(12):1527-35.
3. Agaimy A, Wünsch PH, Hofstaedter F, Blaszyk H, Rümmele P, Gaumann A, et al. Minute gastric sclerosing stromal tumors (GIST tumorlets) are common in adults and frequently show c-KIT mutations. Am J Surg Pathol. 2007;31(1):113-20.
4. Joensuu H, Vehtari A, Riihimäki J, Nishida T, Steigen SE, Brabec P, et al. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. Lancet Oncol. 2012;13(3):265-74.
5. 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.
6. 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.
7. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003(5607); 299:708-10.
8. 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.
9. DeMatteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, et al. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet. 2009;373(9669):1097-104.
10. Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, et al. Twelve vs. 36 months of adjuvant imatinib as treatment of operable GIST with a high risk of recurrence: Final results of a randomized trial (SSGXVIII/AIO). JAMA. 2012;307(12):1265-72.
11. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347(7):472-80.
12. Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumour. Lancet. 2013;382(9896):973-83.
13. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364(9440):1127-34.
14. 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.
15. Debiec-Rychter M, Sciot R, Le Cesne A, Schlemmer M, Hohenberger P, van Oosterom AT, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006;42(8):1093-103.
16. Cassier PA, Fumagilli E, Rutkowski P, Schöffski P, van Glabbeke M, Debiec-Rychter M, et al. Outcome of patients with platelet-derived growth factor receptor alpha-mutated gastrointestinal stromal tumors in the tyrosine kinase inhibitor era. Clin Cancer Res. 2012;18(16):4458-64.
17. Gastrointestinal stromal tumours: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. ESMO/European Sarcoma Network Working Group. Ann Oncol. 2014;25(Suppl 3):iii21-6.
18. 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.
19. Von Mehren M. Follow-up results after 9 years of the ongoing, phase II B2222 trial of imatinib mesylate in patients with metastatic or unresectable KIT+ gastrointestinal stromal tumors (GIST). J Clin Oncol. 2011;29(15S):609s (abstract #10016).
20. Le Cesne A, Ray-Coquard I, Buy BN, Adenis A, Rios M, Bertucci F, et al. Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol. 2010;11(10):942-9.
21. Kang YK, Ryu MH, Yoo C, Ryoo BY, Kim HJ, Lee JJ, et al. Resumption of imatinib to control metastatic or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib (RIGHT): a randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2013;14(12):1175-82.
22. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006;368(9544):1329-38.
23. Sodergren SC, White A, Efficace F, Sprangers M, Fitzsimmons D, Bottomley A, et al. Systematic review of the side effects associated with tyrosine kinase inhibitors used in the treatment of gastrointestinal stromal tumours on behalf of the EORTC Quality of Life Group. Crit Rev Oncol Hematol. 2014;91(1):35-46.
24. George S, Blay JY, Casali PG, Le Cesne A, Stephenson P, Deprimo SE, et al. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer. 2009;45(11):1959-68.
25. Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, Gelderblom H, et al. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):295-302.
26. Shah RR, Morganroth J, Shah DR. Hepatotoxicity of tyrosine kinase inhibitors: clinical and regulatory perspectives. Drug Saf. 2013;36(7):491-503.
27. Debiec-Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005;128(2):270-9.
28. Heinrich MC, Corless CL, Blanke CD, Demetri GD, Joensuu H, Roberts PJ, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006;24(29):4764-74.
29. Gajiwala KS, Wu JC, Christensen J, Deshmukh GD, Diehl W, DiNitto JP, et al. KIT kinase mutants show unique mechanisms of drug resistance to imatinib and sunitinib in gastrointestinal stromal tumor patients. Proc Natl Acad Sci USA. 2009;106(5):1542-7.
30. Garner AP, Gozgit JM, Anjum R, Vodala S, Schrock A, Zhou T, et al. Ponatinib inhibits polyclonal drug-resistant KIT oncoproteins and shows therapeutic potential in heavily pretreated gastrointestinal stromal tumor (GIST) patients. Clin Cancer Res. 2014;20(22):5745-55.
31. Heinrich MC, Corless C, Liegl B, Fletcher CD, Raut CP, Donsky R, et al. Mechanisms of sunitinib malate resistance in gastrointestinal stromal tumors (GISTs). J Clin Oncol. 2007;25(18S):546s (abstract #10006).
32. Wardelmann E, Thomas N, Merkelbach-Bruse S, Pauls K, Speidel N, Büttner R, et al. Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol. 2005;6(4):249-51.
33. Liegl B, Kepten I, Le C, Zhu M, Demetri GD, Heinrich MC, et al. Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 2008;216(1):64-74.
34. 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.
35. Serrano C, Wang Y, Marino-Enriquez A, Lee JC, Ravegnini G, Morgan JA, et al. KRAS and KIT gatekeeper mutations confer polyclonal primary imatinib resistance in GI stromal tumors: relevance of concomitant phosphatidylinositol 3-kinase/AKT dysregulation. J Clin Oncol. 2014 (Epub ahead of print).
36. Reichardt P, Blay JY, Gelderblom H, Schlemmer M, Demetri GD, Bui-Nguyen B, et al. Phase III study of nilotinib versus best supportive care with or without a TKI in patients with gastrointestinal stromal tumors resistant to or intolerant of imatinib and sunitinib. Ann Oncol. 2012;23(7):1680-7.
37. Blay JY. Phase III trial of nilotinib versus imatinib as first-line targeted therapy of advanced gastrointestinal stromal tumors (GIST). J Clin Oncol. 2013;31(15S):632s (abstract #10501).
38. Montemurro M, Schöffski P, Reichardt P, Gelderblom H, Schütte J, Hartmann JT, et al. Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. Eur J Cancer. 2009;45(13):2293-7.
39. 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.
40. Le Cesne A, Blay JY, Bui BN, Bouché O, Adenis A, Domont J, et al. Phase II study of oral masitinib mesilate in imatinib-naïve patients with locally advanced or metastatic gastro-intestinal stromal tumour (GIST). Eur J Cancer. 2010;46(8):1344-51.
41. Adenis A, Blay JY, Bui-Nguyen B, Bouché O, Bertucci F, Isambert N, et al. Masitinib in advanced gastrointestinal stromal tumor (GIST) after failure of imatinib: a randomized controlled open-label trial. Ann Oncol. 2014;25(9):1762-9.
42. 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.
43. Montemurro M, Gelderblom H, Bitz U, Schütte J, Blay JY, Joensuu H, et al. Sorafenib as third- or fourth-line treatment of advanced gastrointestinal stromal tumour and pretreatment including both imatinib and sunitinib, and nilotinib: A retrospective analysis. Eur J Cancer. 2013;49(5):1027-31.
44. Reichardt P, Montemurro M, Gelderbloom H, Blay J, Rutkowski P, Bui B, et al. Sorafenib fourth-line treatment in imatinib-, sunitinib-, and nilotinib-resistant metastatic GIST: A retrospective analysis. J Clin Oncol. 2009;27:551s (abstract #10564).
45. Kindler HL. Sorafenib in patients with imatinib and sunitinib resistant gastrointestinal stromal tumors (GIST): final results of a University of Chicago phase II consortium trial. J Clin Oncol. 2011;29(15S):607s (abstract #10009).
46. Kang YK, Yoo C, Ryoo BY, Lee JJ, Tan E, Park I, et al. Phase II study of dovitinib in patients with metastatic and/or unresectable gastrointestinal stromal tumours after failure of imatinib and sunitinib. Br J Cancer. 2013;109(9):2309-15.
47. Joensuu H, Blay JY, Comandone A, Broto JM, Fumagalli E, Grignani E, et al. Phase 2 trial to evaluate the efficacy and safety of dovitinib in patients with gastrointestinal stromal tumor refractory and/or intolerant to imatinib. Ann Oncol. 2014;25(Suppl 4). doi: 10.1093/annonc/mdu438.58 (abstract #LBA46).
48. Kumar R, Knick VB, Rudolph SK, Johnson JH, Crosby RM, Crouthamel MC, et al. Pharmacokinetic-pharmacodynamic correlation from mouse to human with pazopanib, a multikinase angiogenesis inhibitor with potent antitumor and antiangiogenic activity. Mol Cancer Ther. 2007;6(7):2012-21.
49. Ganjoo KN, Villalobos VM, Kamaya A, Fisher GA, Butrynski JE, Morgan JA, et al. A multicenter phase II study of pazopanib in patients with advanced gastrointestinal stromal tumors (GIST) following failure of at least imatinib and sunitinib. Ann Oncol. 2014;25(1):236-40.
50. Blay J. Final results of the multicenter randomized phase II PAZOGIST trial evaluating the efficacy of pazopanib plus best supportive care vs BSC alone in resistant unresectable metastatic and/or locally advanced gastrointestinal stromal tumors (GIST). J Clin Oncol. 2015;33(15S):561s (abstract #10506).
51. Cortes JE, Kantarjian H, Shah NP, Bixby D, Mauro MJ, Flinn I, et al. Ponatinib in refractory Philadelphia chromosome-positive leukemias. N Engl J Med. 2012;367(22):2075-88.
52. Heinrich MC, Von Mehren M, Demetri GD, Fletcher JA, Sun J, Hodgson G, et al. A phase 2 study of ponatinib in patients with advanced gastrointestinal stromal tumors (GIST) after failure of tyrosine kinase inhibitor (TKI) therapy: initial report. J Clin Oncol. 2014;32(15S):669s (abstract #10506).
53. Shah NP, Talpaz M, Deininger MW, Mauro MJ, Flinn IW, Bixby D, et al. Ponatinib in patients with refractory acute myeloid leukaemia: findings from a phase 1 study. Br J Haematol. 2013;162(4):548-52.
54. Nokhara H, Yamamoto N, Nakamichi S, Wakus H, Yamada Y, Nguyen L, et al. A phase 1 study of cabozantinib in japanese patients with advanced solid tumors: anti-tumor activity in NSCLC and GIST. Ann Oncol 2013;24(suppl 9):ix48.
55. Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012;13(9):897-905.
56. Zhou A, Zhang W, Chang C, Chen X, Zhong D, Qin Q, et al. Phase I study of the safety, pharmacokinetics and antitumor activity of famitinib. Cancer Chemother Pharmacol. 2013;72(5):1043-53.
57. 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.
58. Lindauer M, Hochhaus A. Dasatinib. Recent Results Cancer Res. 2010;184:83-102.
59. Montemurro M, Cioffi A, Domont J, Rutkowski P, Roth AD, von Moos R, et al. Long-term outcome of dasatinib first-line treatment in gastrointestinal stromal tumors: a multicenter two stage phase II trial SAKK 56/07. Ann Oncol. 2014;25(Suppl. 4):iv496 (abstract #1418PD).
60. Trent JC. A phase II study of dasatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST). J Clin Oncol. 2011;29(15S):606s (abstract #10006).
61. Evans EK, Hodous BL, Gardino A, Zhu J, Shutes A, Davis A, et al. First selective KIT D816V inhibitor for patients with systemic mastocytosis. Blood. 2014;124(21):3217 (#abstract 3217).
62. Heinrich MC, Griffith D, McKinley A, Patterson J, Presnell A, Ramachandran A, et al. Crenolanib inhibits the drug-resistant PDGFRA D842V mutation associated with imatinib-resistant gastrointestinal stromal tumors. Clin Cancer Res. 2012;18(16):4375-84.
63. Matro JM, Yu JQ, Heinrich MC, Ramachandran A, Ku N, von Mehren M. Correlation of PET/CT and CT RECIST response in GIST patient with PDGFRA D842V gene mutations treated with crenolanib. J Clin Oncol. 2014;32(15S):679s (abstract #10546).
64. Collins R, Kantarjian HM, Levis MJ, Perl AE, Ramachandran A, Ravendi F, et al. Clinical activity of crenolanib in patients with D835 mutant FLT3-positive relapsed/refractory acute myeloid leukemia (AML). J Clin Oncol. 2014;32(15S)451s (abstract #7027).
65. Workman P. Altered states: selectively drugging the Hsp90 cancer chaperone. Trends Mol Med. 2004;10(2):47-51.
66. Kamal A, Boehm MF, Burrows FJ. Therapeutic and diagnostic implications of Hsp90 activation. Trends Mol Med. 2004;10(6):283-90.
67. Bauer S, Yu LK, Demetri GD, Fletcher JA. Heat shock protein 90 inhibition in imatinib-resistant gastrointestinal stromal tumor. Cancer Res. 2006;66(18):9153-61.
68. Marino-Enriquez A, Ou WB, Cowley G, Luo B, Jonker AH, Mayeda M, et al. Genome-wide functional screening identifies CDC37 as a crucial HSP90-cofactor for KIT oncogenic expression in gastrointestinal stromal tumors. Oncogene. 2014;33(14):1872-6.
69. Wagner AJ, Chugh R, Rosen LS, Morgan JA, George S, Gordon M, et al. A phase I study of the HSP90 inhibitor retaspimycin hydrochloride (IPI-504) in patients with gastrointestinal stromal tumors or soft-tissue sarcomas. Clin Cancer Res. 2013;19(21):6020-9.
70. Demetri GD, Heinrich MC, Chmielowski, Morgan JA, George S, Bradley R, et al. An open-label phase II study of Hsp90 inhibitor ganetespib (STA-9090) in patients with metastatic and/or unresectable GIST. J Clin Oncol. 2011;29(15S):607s (abstract #10011).
71. Dickson MA, Okuno SH, Keohan ML, Maki RG, D'Adamo DR, Akhurst TJ, et al. Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors. Phase II study of the HSP90-inhibitor BIIB021 in gastrointestinal stromal tumors. Ann Oncol. 2013;24(1):252-7.
72. Smyth T, Van LT, Curry JE, Rodriguez-Lopez AM, Wozniak A, Zhu M, et al. (2012). The HSP90 inhibitor, AT13387, is effective against imatinib-sensitive and -resistant gastrointestinal stromal tumor models. Mol Cancer Ther. 2012;11(8):1799-808.
73. Shapiro GI, Kwak E, Dezube BJ, Yule M, Ayrton J, Lyons J, et al. First-in-human phase I dose escalation study of a second-generation non-ansamycin HSP90 inhibitor, AT13387, in patients with advanced solid tumors. Clin Cancer Res. 2015;21(1):87-97.
74. Marks P, Rifkind RA, Richon VM, Breslow R, Miller T, Kelly WK. Histone deacetylases and cancer: causes and therapies. Nat Rev Cancer. 2001;1(3):194-202.
75. Johnstone RW. Histone-deacetylase inhibitors: novel drugs for the treatment of cancer. Nat Rev Drug Discov. 2001;1(4):287-99.
76. Kovacs JJ, Murphy PJ, Gaillard S, Zhao X, Wu JT, Nicchitta CV, et al. HDAC6 regulates Hsp90 acetylation and chaperone-dependent activation of glucocorticoid receptor. Mol Cell. 2005;18(5):601-7.
77. Muhlenberg T, Zhang Y, Wagner AJ, Grabellus F, Bradner J, Taeger G, et al. Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors. Cancer Res. 2009;69(17):6941-50.
78. Floris G, Debiec-Rychter M, Sciot R, Stefan C, Fieuws S, Machiels K, et al. High efficacy of panobinostat towards human gastrointestinal stromal tumors in a xenograft mouse model. Clin Cancer Res. 2009;15(12):4066-76.
79. Bauer S, Hilger RA, Mühlenberg T, Grabellus F, Nagarajah J, Hoiczyk M, et al. Phase I study of panobinostat and imatinib in patients with treatment-refractory metastatic gastrointestinal stromal tumors. Br J Cancer. 2014;110(5):1155-62.
80. Bai Y, Bandara G, Ching Chan E, Maric I, Simakova O, Bandara SN, et al. Targeting the KIT activating switch control pocket: a novel mechanism to inhibit neoplastic mast cell proliferation and mast cell activation. Leukemia. 2013;27(2):278-85.
81. 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. (2004). J Biol Chem. 2004;279(30):31655-63.
82. Heinrich MC, Wise S, Hood M, Smith B, Kaufman M, Lu W, et al. In vitro activity of novel KIT/PDGFRA switch pocket kinase inhibitors against mutations associated with drug-resistant GI stromal tumors. J Clin Oncol. 2010;28(15S):699s (#abstract 10007).
83. Bauer S, Duensing A, Demetri GD, Fletcher JA. KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene. 2007;26(54):7560-8.
84. Chi P, Chen Y, Zhang L, Guo X, Wongvipat J, Shamu T, et al. ETV1 is a lineage survival factor that cooperates with KIT in gastrointestinal stromal tumours. Nature. 2010;467(7317):849-53.
85. Ran L, Sirota I, Cao Z, Murphy D, Chen Y, Shukla S, et al. Combined inhibition of MAP kinase and KIT signaling synergistically destabilizes ETV1 and suppresses GIST tumor growth. Cancer Discov. 2015;5(3):304-15.
86. Miranda C, Nucifora M, Molinari F, Conca E, Anania MC, Bordoni A, et al. KRAS and BRAF mutations predict primary resistance to imatinib in gastrointestinal stromal tumors. Clin Cancer Res. 2012;18(6):1769-76.
87. Andersson J, Sihto H, Meis-Kindblom JM, Joensuu H, Nupponen N, Kindblom LG. NF1-associated gastrointestinal stromal tumors have unique clinical, phenotypic, and genotypic characteristics. Am J Surg Pathol. 29(9):1170-6.
88. Daniels M, Lurkin I, Pauli R, Erbstosser E, Hildebrandt U, Hellwig K, et al. Spectrum of KIT/PDGFRA/BRAF mutations and phosphatidylinositol-3-kinase pathway gene alterations in gastrointestinal stromal tumors (GIST). Cancer Lett. 2011;312(1):43-54.
89. Schoffski P, Reichardt P, Blay JY, Dumez H, Morgan JA, Ray-Coquard I, et al. A phase I-II study of everolimus (RAD001) in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors. Ann Oncol. 2010;21(10):1990-8.
90. Chi P. A phase Ib/II study of MEK162 (binimetinib) in combination with imatinib in patients with advanced gastrointestinal stromal tumor (GIST). J Clin Oncol. 2015;33(15S):561s (abstract #10507).
91. Shoushtari AN, D'Angelo SP, Keohan ML, Dickson MA, Gounder MM, Abdullah AK, et al. Combined KIT and CTLA-4 blocade in patients with refractory GIST and other advanced sarcomas. J Clin Oncol. 2014;32(15S):673s (abstract#10521).
92. Borg C, Terme M, Taieb J, Menard C, Flament C, Robert C, et al. Novel mode of action of c-kit tyrosine kinase inhibitors leading to NK cell-dependent antitumor effects. J Clin Invest. 2014;114(3):379-88.
93. Rusakiewicz S, Semeraro M, Sarabi M, Desbois M, Locher C, Mendez R, et al. Immune infiltrates are prognostic factors in localized gastrointestinal stromal tumors. Cancer Res. 2014;73(12):3499-510.
94. Schneider-Stock R, Boltze C, Lasota J, Miettinen M, Peters B, Pross M, et al. High prognostic value of p16INK4 alterations in gastrointestinal stromal tumors. J Clin Oncol. 2003;21(9):1688-97.
95. Konecny GE, Winterhoff B, Kolarova T, Qi J, Manivong K, Dering J, et al. Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer. Clin Cancer Res. 2011;17(6):1591-602.
96. Javidi-Sharifi N, Traer E, Martinez J, Gupta A, Taguchi T, Dunlap J, et al. Crosstalk between KIT and FGFR3 promotes gastrointestinal stromal tumor cell growth and drug resistance. Cancer Res. 2015;75(5):880-91.
97. Li F, Huynh H, Li X, Ruddy DA, Wang Y, Ong R, et al. FGFR-mediated reactivation of MAPK signaling attenuates antitumor effects of imatinib in gastrointestinal stromal tumors. Cancer Discov. 2015.pii:CD-14-0763 (Epub ahead of print).
98. Henze J, Muhlenberg T, Simon S, Grabellus F, Rubin B, Taeger G, et al. p53 modulation as a therapeutic strategy in gastrointestinal stromal tumors. PLoS One. 2012;7(5):e37776.
99. 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.
100. Bauer S, Rutkowski P, Hohenberger P, Miceli R, Fumagalli E, Siedlecki JA, et al. Long-term follow-up of patients with GIST undergoing metastasectomy in the era of imatinib - analysis of prognostic factors (EORTC-STBSG collaborative study). Eur J Surg Oncol. 2014;40(4):412-9.