ライフサイエンスコーパス: crizotinib

1 raterone acetate, ruxolitinib phosphate, and crizotinib).

2 sponse to tyrosine kinase inhibitors such as crizotinib.

3 , and the ETV6-NTRK3 fusion was sensitive to crizotinib.

4 hs while on treatment with the ALK inhibitor crizotinib.

5 SCLC who progressed on or were intolerant to crizotinib.

6 were detected in patients being treated with crizotinib.

7 mall-molecule ALK kinase inhibitors, such as crizotinib.

8 were monitored in five patients treated with crizotinib.

9 the recent FDA approval of the ALK inhibitor crizotinib.

10 arrangement to the tyrosine kinase inhibitor crizotinib.

11 CD74-ROS1 showed evidence of sensitivity to crizotinib.

12 the resistance of ALK(F1174L)/MYCN tumors to crizotinib.

13 se domain, rendering EML4-ALK insensitive to crizotinib.

14 ine and at an early time-point (2 months) on crizotinib.

15 ith ALK-positive NSCLC who had progressed on crizotinib.

16 that can be overcome with the MET inhibitor crizotinib.

17 ALK-positive disease who have progressed on crizotinib.

18 received crizotinib, or as an alternative to crizotinib.

19 ajor partial response to the c-Met inhibitor crizotinib.

20 LK-positive NSCLC who progressed on previous crizotinib.

21 1156Y and resensitizing resistant cancers to crizotinib.

22 ALK-positive NSCLC who had progressed after crizotinib.

23 inhibitors, including the FDA-approved drug crizotinib.

24 arrangement who experience progression after crizotinib.

25 sed controlled trial comparing lorlatinib to crizotinib.

26 ivity in patients resistant or intolerant to crizotinib.

27 (hazard ratio for progression or death with crizotinib, 0.49; 95% confidence interval [CI], 0.37 to

28 Crizotinib (1), an anaplastic lymphoma kinase (ALK) rece

29 positive stage III or IV NSCLC received oral crizotinib 250 mg twice daily in 28-day cycles.

30 omly assigned to receive oral treatment with crizotinib (250 mg) twice daily or intravenous chemother

31 Crizotinib, a first-line therapy in the treatment of adv

32 Crizotinib, a selective tyrosine kinase inhibitor (TKI),

33 ly tractable to translation included ABT-263/crizotinib, ABT-263/paclitaxel, paclitaxel/JQ1, ABT-263/

34 To assess whether crizotinib affects overall survival in these patients, w

35 ion of the plasma pharmacokinetic profile of crizotinib after oral administration.

36 The patient received crizotinib again, and her cancer-related symptoms and li

37 patients from trial sites who were not given crizotinib (ALK-positive controls), 67 patients without

38 ll lung cancer (NSCLC) patients treated with crizotinib, although all patients invariably develop res

39 Crizotinib, an inhibitor of anaplastic lymphoma kinase (

40 associated with marked clinical responses to crizotinib, an oral tyrosine kinase inhibitor targeting

41 n the decrease in CTC number with ALK-CNG on crizotinib and a longer PFS (likelihood ratio test, P =

42 Both crizotinib and BKM120 strongly inhibited the activity of

43 The ALK kinase inhibitors crizotinib and ceritinib are approved for relapsed ALK(+

44 ed with intrinsic and acquired resistance to crizotinib and cosegregates with MYCN in neuroblastoma.

45 ROS1 inhibition with crizotinib and deglutathiolation of SHP-2 abolished GPX1

46 ROS1 kinase domain that confer resistance to crizotinib and demonstrate that these mutants also remai

47 e therapeutic target in PDAC and highlighted crizotinib and gemcitabine as a synergistic combination

48 The multitargeted tyrosine kinase inhibitors Crizotinib and GSK1363089 greatly enhanced the anticance

49 two lines, including a platinum doublet) and crizotinib and had subsequent disease progression, from

50 Moreover, combining crizotinib and imatinib was more effective than imatinib

51 al activity against ALK mutants resistant to crizotinib and other ALK inhibitors.

52 LK(+) patients harboring tumors resistant to crizotinib and other anti-ALK tyrosine kinase inhibitors

53 Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or plan

54 As expected, other c-MET inhibitors, crizotinib and PHA-665752, suppressed the growth of c-ME

55 ncer who had previously progressed following crizotinib and platinum-based doublet chemotherapy.

56 growth can be blocked by the ALK inhibitors crizotinib and TAE684.

57 d more sensitive to the FER kinase inhibitor crizotinib and the epidermal growth factor receptor kina

58 Compared with crizotinib and the second-generation ALK/ROS1 inhibitors

59 de was more efficient than the MET inhibitor crizotinib and/or the VEGFR-2 inhibitor pazopanib in red

60 ion with platinum and either before or after crizotinib) and had a response rate of 57.7% and a media

61 kinase inhibitors (JNJ-38877605, PHA-665752, crizotinib) and one antagonistic anti-MET antibody (DN30

62 ems and overcame resistance to JNJ-38877605, crizotinib, and DN30 Fab in human HGF knock-in mice.

63 a more potent ALK inhibitor after failure of crizotinib, and establish ceritinib as a more efficaciou

64 lerated dose, to define the toxic effects of crizotinib, and to characterise the pharmacokinetics of

65 DK378), which are structurally distinct from crizotinib, are active against NB cells expressing ALK(F

66 tyrosine kinase inhibitors (TKI), including crizotinib, are effective treatments in preclinical mode

67 hibitors, we identified the kinase inhibitor crizotinib as a nanomolar suppressor of MTH1 activity.

68 In addition, the role of crizotinib as a potential binding inhibitor is demonstra

69 Administration (FDA)-approved ALK inhibitor crizotinib as a ROS1 inhibitor.

70 Our results propose (S)-crizotinib as an attractive chemical entity for further

71 vival showed no significant improvement with crizotinib as compared with chemotherapy (hazard ratio f

72 e ALK-rearranged NSCLC patients treated with crizotinib as first ALK inhibitor were recruited prospec

73 progression were permitted to cross over to crizotinib as part of a separate study.

74 ified tumors to the small molecule inhibitor crizotinib as part of an expanded phase I cohort study.

75 ponse rates were 65% (95% CI, 58 to 72) with crizotinib, as compared with 20% (95% CI, 14 to 26) with

76 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated

77 owed that MPM cells were highly sensitive to crizotinib, BKM120 and GDC-0980 when used individually a

78 e kinase inhibitors (ALK inhibitors) such as crizotinib, but resistance invariably develops, often wi

79 stablished a model of acquired resistance to crizotinib by exposing a highly sensitive EML4-ALK-posit

80 Mechanistic investigations of the ABT-263/crizotinib combination offering a potentially rapid path

81 ALK-copy number gain (ALK-CNG)] monitored on crizotinib could predict progression-free survival (PFS)

82 In particular, we found that crizotinib decreased tumor dimension, prolonged survival

83 Although crizotinib demonstrates robust efficacy in anaplastic ly

84 hat cells resistant to intermediate doses of crizotinib developed amplification of the EML4-ALK gene.

85 (ALK)-rearranged lung cancer, resistance to crizotinib developed because of a mutation in the ALK ki

86 Resistance to crizotinib developed in a patient with metastatic lung a

87 eated with the specific MET kinase inhibitor crizotinib developed resistance resulting from compensat

88 , which on one hand, impaired the binding of crizotinib directly, and on the other hand, shortened th

89 ose escalation had established a recommended crizotinib dose of 250 mg twice daily in 28-day cycles.

90 th ALK-CNG may be a predictive biomarker for crizotinib efficacy in ALK-rearranged NSCLC patients.

91 ients with MET-amplified tumors treated with crizotinib experienced tumor shrinkage (-30% and -16%) a

92 However, crizotinib fails to effectively inhibit the activity of

93 ho enrolled in the phase 1 clinical trial of crizotinib, focusing on the cohort of 82 patients who ha

94 for chondrosarcoma, small molecule inhibitor crizotinib for anaplastic lymphoma kinase (ALK)-rearrang

95 39 patients continued to receive crizotinib for more than 2 weeks after progression becau

96 b for those with sensitizing EGFR mutations; crizotinib for those with ALK or ROS1 gene rearrangement

97 gression-free survival was 7.7 months in the crizotinib group and 3.0 months in the chemotherapy grou

98 chemotherapy (hazard ratio for death in the crizotinib group, 1.02; 95% CI, 0.68 to 1.54; P=0.54).

99 Whereas crizotinib has demonstrated promising early results in p

100 The recently approved ALK kinase inhibitor crizotinib has demonstrated successful treatment of meta

101 , median overall survival from initiation of crizotinib has not been reached (95% CI 17 months to not

102 addition, we observed a clinical response to crizotinib in a patient with METDelta14-driven NSCLC, on

103 n the ALK kinase domain confer resistance to crizotinib in about one-third of these patients.

104 Phase I and II studies of crizotinib in ALK-positive lung cancer demonstrated impr

105 and to characterise the pharmacokinetics of crizotinib in children with refractory cancer.

106 ded phase 2 dose, and antitumour activity of crizotinib in children with refractory solid tumours and

107 ny clinical trials, but the effectiveness of crizotinib in CNS disease is limited by poor blood-brain

108 e assessed the activity of the ALK inhibitor crizotinib in patients who had no known curative treatme

109 We assessed the tolerability and activity of crizotinib in patients with NSCLC who were prospectively

110 l in 30 ALK-positive patients who were given crizotinib in the second-line or third-line setting was

111 ase III trial confirmed the high activity of crizotinib in this subset of lung tumors.

112 of the mechanisms of acquired resistance to crizotinib in tumor biopsies.

113 eritinib is a more potent ALK inhibitor than crizotinib in vitro, crosses the blood-brain barrier in

114 ients with ALK-rearranged NSCLC resistant to crizotinib, including those with CNS metastases.

115 pool homeostasis via MTH1 inhibition by (S)-crizotinib induced an increase in DNA single-strand brea

116 ent with BKM120 alone or in combination with crizotinib induced G2-M arrest and apoptosis.

117 Although crizotinib induces remissions and extends the lives of p

118 ily inhibitors with NVP-AEW541, dasatinib or crizotinib (inhibitors of IGF-1R, Src and c-Met/ALK, res

119 Crizotinib inhibits proliferation of ETV6-NTRK3-dependen

120 Crizotinib is a potent inhibitor of both ROS1 and ALK ki

121 Crizotinib is a tyrosine kinase inhibitor of MET, ALK an

122 Crizotinib is superior to standard chemotherapy in patie

123 Whether crizotinib is superior to standard chemotherapy with res

124 Crizotinib is well tolerated with rapid, durable respons

125 -driven malignancies and one such inhibitor, crizotinib, is now approved for the treatment of EML4-AL

126 s with ROS1 gene rearrangement without prior crizotinib may be offered crizotinib, or if they previou

127 mong 82 ALK-positive patients who were given crizotinib, median overall survival from initiation of c

128 Furthermore, the F1174L mutation inhibits crizotinib-mediated downregulation of ALK signaling and

129 biopsy samples from patients progressing on crizotinib monotherapy.

130 file in patients with crizotinib-treated and crizotinib-naive ALK-rearranged NSCLC.

131 has shown clinical activity in patients with crizotinib-naive ALK-rearranged NSCLC.

132 ibitor-showed promising clinical activity in crizotinib-naive and crizotinib-resistant patients with

133 crizotinib-treated patients in the trial and crizotinib-naive controls screened during the same time

134 with improved survival compared with that of crizotinib-naive controls.

135 lities in brigatinib targets (cohort 4), and crizotinib-naive or crizotinib-treated ALK-rearranged NS

136 All eight crizotinib-naive patients with ALK-rearranged NSCLC had

137 2% [38-65]; p=0.786), whereas survival in 36 crizotinib-naive, ALK-positive controls was similar to t

138 er, L1198F paradoxically enhances binding to crizotinib, negating the effect of C1156Y and resensitiz

139 Despite the antitumor activity of crizotinib observed in both ROS1- and ALK-rearranged NSC

140 Emergence of resistance to crizotinib occurs approximately 5-8 months after initiat

141 ALK-targeted therapy with crizotinib offers significant improvement in clinical ou

142 Notably, in the absence of crizotinib or ceritinib, we found that increased ALK sig

143 MET inhibition by crizotinib or RNA interference was cytotoxic to an imati

144 with ALK-rearranged NSCLC who have received crizotinib, or as an alternative to crizotinib.

145 ment without prior crizotinib may be offered crizotinib, or if they previously received crizotinib, t

146 atic or inoperable ALK-positive IMT received crizotinib orally twice daily.

147 ial, the ALK tyrosine kinase inhibitor (TKI) crizotinib (PF-02341066) demonstrated impressive antitum

148 The ALK kinase inhibitor crizotinib (PF-02341066) is clinically effective in pati

149 363089) is a more potent ROS1 inhibitor than crizotinib (PF-02341066), an ALK/ROS inhibitor currently

150 h tumors in an early-phase clinical trial of crizotinib (PF-02341066), an orally available small-mole

151 lead series generated the clinical candidate crizotinib (PF-02341066), which demonstrated potent in v

152 nt sensitivity to the targeted MET inhibitor crizotinib (PF-02341066).

153 tained partial response to the ALK inhibitor crizotinib (PF-02341066, Pfizer) in a patient with ALK-t

154 In ROS1-positive patients, including seven crizotinib-pretreated patients, an objective response wa

155 nst oncogenic ROS1 fusions and inhibited the crizotinib-refractory ROS1(G2032R) mutation and the ROS1

156 rating properties, as well as for overcoming crizotinib resistance driven by ROS1 mutation.

157 evidence suggests that patients may develop crizotinib resistance due to acquired point mutations in

158 ary mutation in ALK, F1174L, as one cause of crizotinib resistance in a patient with an inflammatory

159 ALK inhibitors, which can overcome emergent crizotinib resistance mutations, as well as development

160 rteen relapsed patients revealed three known crizotinib resistance mutations, C1156Y, L1196M and G126

161 tated ROS1 was primarily responsible for the crizotinib resistance, which on one hand, impaired the b

162 The crizotinib-resistant ALK(F1174L) mutation arises de novo

163 istance drivers (including P2Y receptors) in crizotinib-resistant ALK-rearranged lung tumors compared

164 A randomised phase 2 trial in patients with crizotinib-resistant ALK-rearranged NSCLC is prospective

165 tics and robust tumor growth inhibition in a crizotinib-resistant cell line (H3122-L1196M).

166 The crizotinib-resistant DFCI076 cell line harbored a unique

167 nd shows clinical responses in patients with crizotinib-resistant disease.

168 Treatment of crizotinib-resistant NPM-ALK(+) KARPAS-299-CR06 cells wi

169 he drug target, ROS1 tyrosine kinase, from a crizotinib-resistant patient, who responded poorly to cr

170 ng clinical activity in crizotinib-naive and crizotinib-resistant patients with ALK-rearranged (ALK-p

171 r Hsp90 inhibitors are effective in treating crizotinib-resistant tumors harboring secondary gatekeep

172 the dual MET/RON tyrosine kinase inhibitor, crizotinib, restored cetuximab sensitivity in SC.

173 recently reported in clinical resistance to crizotinib, retains foretinib sensitivity at concentrati

174 g loop (P-loop) conformational change of the crizotinib-ROS1 complex through advanced molecular dynam

175 In contrast to crizotinib's dual ROS1/ALK activity, cabozantinib (XL-18

176 d variants also showed differential in vitro crizotinib sensitivities.

177 astoma cells with the dual Met/ALK inhibitor crizotinib sensitized cells to antibody-induced growth i

178 ion trial of the selective MET/ALK inhibitor crizotinib showed a long-term partial response in a pati

179 ial, the ALK tyrosine-kinase inhibitor (TKI) crizotinib showed marked antitumour activity in patients

180 The patient treated with crizotinib showed tumor shrinkage, with a near complete

181 Crizotinib shows in vitro activity and early evidence of

182 n ALK fusion within the first-in-man phase 1 crizotinib study.

183 r improvement in global quality of life with crizotinib than with chemotherapy.

184 e robust and sustained clinical responses to crizotinib therapy in patients with relapsed ALCL and me

185 patients with advanced, ALK-positive NSCLC, crizotinib therapy is associated with improved survival

186 EML4-ALK-positive advanced NSCLC, first-line crizotinib therapy provided 0.379 additional QALYs, cost

187 cent in situ hybridization, and had received crizotinib therapy through an individual off-label use.

188 P2-ALK translocation who progressed while on crizotinib therapy.

189 d crizotinib, or if they previously received crizotinib, they may be offered chemotherapy.

190 bitor-naive ALK-rearranged NSCLC (cohort 1), crizotinib-treated ALK-rearranged NSCLC (cohort 2), EGFR

191 targets (cohort 4), and crizotinib-naive or crizotinib-treated ALK-rearranged NSCLC with active, mea

192 n acceptable safety profile in patients with crizotinib-treated and crizotinib-naive ALK-rearranged N

193 isms of ALK TKI resistance identified from a crizotinib-treated non-small cell lung cancer (NSCLC) pa

194 pective study comparing survival outcomes in crizotinib-treated patients in the trial and crizotinib-

195 Survival in 56 crizotinib-treated, ALK-positive patients was similar to

196 n testing in stage IV nonsquamous NSCLC with crizotinib treatment for ALK-positive patients is not co

197 ents with ALK-rearranged NSCLC with previous crizotinib treatment had an objective response (44 [62%

198 ting in combination with targeted first-line crizotinib treatment in Ontario.

199 Molecular testing with first-line targeted crizotinib treatment in the population with advanced non

200 nt in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies

201 vincristine treatment, whereas PHA-665752 or crizotinib treatment markedly induced G(0)-G(1) cell-cyc

202 Under pressure of crizotinib treatment, point mutations arise in the kinas

203 of FGFR and integrin beta3 are resistant to crizotinib treatment, suggesting that FGFR and integrin

204 ng both diagnostic testing and monitoring of crizotinib treatment.

205 itive NSCLC cell line to increasing doses of crizotinib until resistance emerged.

206 MET activation loop, critical for binding to crizotinib, upon clinical progression.

207 es, cancers eventually develop resistance to crizotinib, usually within 1 y, thereby limiting the pot

208 The mean steady state peak concentration of crizotinib was 630 ng/mL and the time to reach this peak

209 The kinase inhibitor crizotinib was directly conjugated to Dha through its pi

210 Crizotinib was given twice daily without interruption.

211 Crizotinib was highly active at treating lung cancer in

212 Although crizotinib was ineffectual against EML4-ALK harboring th

213 of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase

214 Crizotinib was well tolerated with a recommended phase 2

215 l patients who received at least one dose of crizotinib were evaluable for response; patients complet

216 Common adverse events associated with crizotinib were visual disorder, gastrointestinal side e

217 ficacious than the MET/ALK/RON/ROS inhibitor crizotinib with a distinct pattern of downstream signali

218 mouse model, we showed that a combination of crizotinib with BKM120 was highly synergetic in inhibiti

219 ducted a phase 3, open-label trial comparing crizotinib with chemotherapy in 347 patients with locall

220 herapeutic efficacy of the MET/ALK inhibitor crizotinib, with either a pan-class I PI3K inhibitor, BK

221 b-resistant patient, who responded poorly to crizotinib within a very short therapeutic term.

222 Despite the remarkable clinical activity of crizotinib (Xalkori), the first ALK inhibitor approved i

223 6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori).

224 The MET/ALK/ROS1 inhibitor crizotinib (Xalkori, PF-02341066) has demonstrated promi