ライフサイエンスコーパス: crizotinib

1 ib vs five [22%] of 23 patients treated with crizotinib).

2 raterone acetate, ruxolitinib phosphate, and crizotinib).

3 metastases and those previously treated with crizotinib.

4 1156Y and resensitizing resistant cancers to crizotinib.

5 ALK-positive NSCLC who had progressed after crizotinib.

6 inhibitors, including the FDA-approved drug crizotinib.

7 arrangement who experience progression after crizotinib.

8 ivity in patients resistant or intolerant to crizotinib.

9 and an EGFR-mutant/MET-amplified organoid to crizotinib.

10 sponse to tyrosine kinase inhibitors such as crizotinib.

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

12 hs while on treatment with the ALK inhibitor crizotinib.

13 SCLC who progressed on or were intolerant to crizotinib.

14 were detected in patients being treated with crizotinib.

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

16 were monitored in five patients treated with crizotinib.

17 inomas have shown responses to alectinib and crizotinib.

18 ned to treatment: 125 to alectinib and 62 to crizotinib.

19 the recent FDA approval of the ALK inhibitor crizotinib.

20 arrangement to the tyrosine kinase inhibitor crizotinib.

21 CD74-ROS1 showed evidence of sensitivity to crizotinib.

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

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

24 ilable, clinicians should offer ceritinib or crizotinib.

25 reen, we identified two drugs, ceritinib and crizotinib.

26 vascular growth of ALCL in mice treated with crizotinib.

27 otected ALCL cells from apoptosis induced by crizotinib.

28 sed controlled trial comparing lorlatinib to crizotinib.

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

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

31 that can be overcome with the MET inhibitor crizotinib.

32 ALK-positive disease who have progressed on crizotinib.

33 received crizotinib, or as an alternative to crizotinib.

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

35 LK-positive NSCLC who progressed on previous crizotinib.

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

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

38 42.3 months, 95% CI 31.3-51.3 months) versus crizotinib [11.1 months, 95% CI 7.9-13.0 months (HR 0.41

39 onger treatment duration with alectinib than crizotinib (14.7 months vs 12.6 months, respectively), f

40 ily (reductions to 40 mg and 20 mg allowed); crizotinib 250 mg twice daily (reductions to 200 mg twic

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

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

43 1) to twice-daily oral alectinib (600 mg) or crizotinib (250 mg).

44 ignment to the savolitinib (29 patients) and crizotinib (28 patients) groups was halted after a presp

45 response rate was significantly better with crizotinib (a tyrosine kinase inhibitor) than with the c

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

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

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

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

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

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

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

53 Crizotinib also slowed the growth of glioma cells implan

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

55 Crizotinib, an ALK/ROS1/MET inhibitor, is highly effecti

56 Crizotinib, an inhibitor of anaplastic lymphoma kinase (

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

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

59 Both crizotinib and BKM120 strongly inhibited the activity of

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

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

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

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

64 xenograft models, combination treatments of crizotinib and etomoxir, and crizotinib and gamitrinib w

65 n treatments of crizotinib and etomoxir, and crizotinib and gamitrinib were significantly more effica

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

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

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

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

70 the ROS1 kinase domain confer resistance to crizotinib and lorlatinib in more than one-third of acqu

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

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

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

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

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

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

77 ording to their ability to access lysosomes (crizotinib and tepotinib) or not (capmatinib and savolit

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

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

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

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

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

83 ving cabozantinib, ten (37%) of 27 receiving crizotinib, and 11 (39%) of 28 receiving savolitinib; on

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

85 older with advanced NSCLC, prior exposure to crizotinib, and Eastern Cooperative Oncology Group Perfo

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

87 with the MET kinase inhibitors cabozantinib, crizotinib, and savolitinib for treatment of patients wi

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

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

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

91 nly Asian patients to compare alectinib with crizotinib as a first-line treatment for ALK-positive no

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

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

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

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

96 nbiased screen identifying high-dose (10 uM) crizotinib as an ICD-inducing tyrosine kinase inhibitor

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

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

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

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

101 1-52) of 40 patients previously treated with crizotinib as their only TKI had an objective response.

102 TKI-naive, 40 (58%) had previously received crizotinib as their only TKI, and eight (12%) had previo

103 G2032R mutation which is highly resistant to crizotinib as well as lorlatinib and entrectinib, next g

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

105 82 patients (77%) were continuing to receive crizotinib at the time of data cutoff, and the estimated

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

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

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

109 tion of PTPN1 or PTPN2 induces resistance to crizotinib by hyperactivating SHP2, the MAPK, and JAK/ST

110 multikinase inhibitors: imatinib, dasatinib, crizotinib, cabozantinib, and axitinib.

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

112 erivatives bearing phenylbutyrate and either crizotinib (complex 3) or ceritinib (complex 7) exhibite

113 Mechanistic investigations revealed that crizotinib-containing complexes induced G2/M arrest, whe

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

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

116 Although crizotinib demonstrates robust efficacy in anaplastic ly

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

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

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

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

121 Savolitinib and crizotinib did not improve PFS compared with sunitinib.

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

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

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

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

126 However, crizotinib fails to effectively inhibit the activity of

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

128 g in conventional chemotherapy together with crizotinib, followed by immune checkpoint blockade may b

129 Neoadjuvant darovasertib and crizotinib, followed by plaque brachytherapy.

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

131 39 patients continued to receive crizotinib for more than 2 weeks after progression becau

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

133 ger in the alectinib group compared with the crizotinib group (HR 0.37, 0.22-0.61; p<0.0001).

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

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

136 ib group, and 15.0 months (12.5-17.3) in the crizotinib group.

137 Whereas crizotinib has demonstrated promising early results in p

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

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

140 ignificantly prolonged with alectinib versus crizotinib (hazard ratio [HR] 0.22, 95% CI 0.13-0.38; p<

141 nger duration of response for alectinib than crizotinib (HR 0.22, 95% CI 0.12-0.40; p<0.0001).

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

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

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

145 ro and in vivo efficacy than cabozantinib or crizotinib in both models.

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

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

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

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

150 , phase III trial evaluated alectinib versus crizotinib in patients with advanced ALK-positive non-sm

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

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

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

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

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

156 trial of the first generation ALK inhibitor, crizotinib, in neuroblastoma patients showed modest resu

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

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

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

160 The combination of cisplatin and high-dose crizotinib induces ICD in non-small cell lung carcinoma

161 Although crizotinib induces remissions and extends the lives of p

162 c (shRNA and CRISPR/Cas9) and pharmacologic (crizotinib) inhibition of c-MET.

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

164 Crizotinib inhibits proliferation of ETV6-NTRK3-dependen

165 In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of

166 Crizotinib is a multikinase inhibitor with potent activi

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

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

169 roup of NSCLCs for which MET inhibition with crizotinib is active.

170 Crizotinib is superior to standard chemotherapy in patie

171 Whether crizotinib is superior to standard chemotherapy with res

172 Crizotinib is well tolerated with rapid, durable respons

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

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

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

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

177 biopsy samples from patients progressing on crizotinib monotherapy.

178 dian follow-up of 53.5 (alectinib) and 23.3 (crizotinib) months, median OS was 81.1 [95% confidence i

179 A total of 303 patients (alectinib, n = 152; crizotinib, n = 151) were enrolled.

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

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

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

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

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

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

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

187 2% [38-65]; p=0.786), whereas survival in 36 crizotinib-naive, ALK-positive controls was similar to t

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

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

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

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

192 patients and 12 (50%; 29-71) of 24 previous crizotinib-only patients.

193 plexes conjugated with the kinase inhibitors crizotinib or ceritinib were synthesized and assessed fo

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

195 king ALK with clinically available compounds crizotinib or lorlatinib reversed thermal hyperalgesia a

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

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

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

199 assigned to receive sunitinib, cabozantinib, crizotinib, or savolitinib, with stratification by recei

200 s) were assigned to sunitinib, cabozantinib, crizotinib, or savolitinib.

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

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

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

204 363089) is a more potent ROS1 inhibitor than crizotinib (PF-02341066), an ALK/ROS inhibitor currently

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

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

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

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

209 Crizotinib plus cisplatin leads to an increase in the ex

210 notecan selectively inhibited hOCT1, whereas crizotinib potently inhibited hOCT3-mediated mIBG uptake

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

212 Because crizotinib-refractory patients have few treatment option

213 (e.g., ROS1-G2032R) have been identified in crizotinib-refractory patients.

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

215 ivity and is well tolerated in patients with crizotinib-refractory, ALK-positive NSCLC, including tho

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

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

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

219 However, crizotinib resistance is an emerging issue, and several

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

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

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

223 high activity against a broad range of known crizotinib-resistant ALK mutations and CNS metastases.

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

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

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

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

228 The crizotinib-resistant DFCI076 cell line harbored a unique

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

230 associations between ensartinib efficacy and crizotinib-resistant mutations were also explored.

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

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

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

234 nged cancer in preclinical models, including crizotinib-resistant ROS1 positive cancer with secondary

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

236 s 30.9 (n = 53) months with alectinib versus crizotinib, respectively (HR 0.68; 95% CI 0.40-1.15); wi

237 ective inhibition of RET (selpercatinib) and crizotinib, respectively, in patients with histiocytosis

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

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

240 eight (12%) had previously received one non-crizotinib ROS1 TKI or two or more ROS1 TKIs.

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

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

243 d variants also showed differential in vitro crizotinib sensitivities.

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

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

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

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

248 Crizotinib shows in vitro activity and early evidence of

249 harmacological inhibition of NUDT1 using (S)-Crizotinib significantly decreased pulmonary vascular re

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

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

252 kinase inhibitors (Ibrutinib, Dasatinib and Crizotinib) that substantially impaired intracellular ba

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

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

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

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

257 non-small-cell lung cancer (NSCLC), in whom crizotinib therapy was unsuccessful.

258 NSCLC that had progressed while they were on crizotinib therapy, an Eastern Cooperative Oncology Grou

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

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

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

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

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

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

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

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

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

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

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

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

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

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

273 Given the response following crizotinib treatment observed in this case, the kinase f

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

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

276 ng both diagnostic testing and monitoring of crizotinib treatment.

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

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

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

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

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

282 Crizotinib was given twice daily without interruption.

283 Crizotinib was highly active at treating lung cancer in

284 Although crizotinib was ineffectual against EML4-ALK harboring th

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

286 Crizotinib was well tolerated with a recommended phase 2

287 The antitumor activity and safety of crizotinib were assessed in 69 patients with advanced NS

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

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

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

291 Combination of crizotinib with a SHP2 inhibitor synergistically inhibit

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

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

294 125 with alectinib, and 48 (77%) of 62 with crizotinib, with a longer duration of response for alect

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

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

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

298 6-NTRK3 as a target of the FDA-approved drug crizotinib (Xalkori).

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

300 rbor ALK aberrations clinically resistant to crizotinib yet sensitive pre-clinically to the third-gen