ライフサイエンスコーパス: TKI

1 TKIs benefit the majority of patients with advanced GIST

2 TKIs inhibited [(3)H]uridine uptake in a competitive man

3 observational study designed to evaluate 2G-TKI discontinuation in chronic myeloid leukemia (CML).

4 ts the highest chance to remain free from 2G-TKI therapy.

5 scontinuation of first-line or subsequent 2G-TKI yields promising TFR rates without safety concerns.

6 tion (baseline) on treatment response in 363 TKI-resistant patients enrolled in the PONATINIB for Chr

7 Among 31 patients treated with a TKI who had myocardial infarction, 26 (84%) had at least

8 was seen in patients with CML treated with a TKI.

9 dipyridamole binding, suggested that BCR-ABL TKIs interacted with Met(33) (TM1) and Leu(442) (TM11) r

10 In conclusion, BCR-ABL TKIs variously inhibit five different hNTs, cause a decr

11 Imatinib, the first BCR-ABL1 TKI granted regulatory approval, has been surpassed in t

12 erm therapy, where they may promote acquired TKI resistance, drive relapse or disease progression, an

13 0% of days covered during the 6 months after TKI initiation.

14 ations detectable by mass spectrometry after TKI resistance is associated with response to ponatinib

15 ations detectable by mass spectrometry after TKI resistance.

16 s) have demonstrated potent activity against TKI resistance mediated by EGFR T790M.

17 e of first line ALK TKI therapy, another ALK TKI is administered, though collateral sensitivity is no

18 Currently, after failure of first line ALK TKI therapy, another ALK TKI is administered, though col

19 A 'drug holiday' where the ALK TKI treatment is suspended could represent a therapeutic

20 lung cancer line (H3122) to a panel of 4 ALK TKIs, and performed a collateral sensitivity analysis.

21 ilable TKIs, including second-generation ALK TKIs, and is being investigated in a phase 3 randomised

22 Among TKI initiators, 61% were adherent; adherence was lower f

23 T3/ITD(+) cells upon treatment with ATRA and TKI.

24 s a significant clinical problem in CML, and TKI therapy is much less effective against Ph(+)B-cell a

25 ine treatment initiation within 180 days and TKI adherence among initiators.

26 n and intensive regimens of chemotherapy and TKIs, may be more advantageous in children as a way to a

27 ated with radiotherapy (SRS and/or WBRT) and TKIs have prolonged survival, suggesting that interventi

28 establish criteria for safe and appropriate TKI cessation.

29 Tumor cells are TKI-sensitive or TKI-refractory, exhibit intrinsic or ac

30 have become resistant to currently available TKIs, including second-generation ALK TKIs, and is being

31 autocrine loop promote CML-primitive cells' TKI resistance.

32 verall, our findings show how VGF can confer TKI resistance and trigger EMT, suggesting its potential

33 Growth-factor signaling also conferred TKI resistance and induced FOS and DUSP1 expression in t

34 Because CML patients may need to continue TKI therapy indefinitely, the long-term safety of each t

35 e in the patient's best interest to continue TKI, as well as criteria for a safe TFR attempt.

36 ion, and most CML patients require continued TKI treatment to maintain remission.

37 ture health care costs as long as continuous TKI treatment is required.

38 Newly developed TKI can target Ph(+) ALL cells with BCR-ABL1-dependent r

39 resent in chronic phase (CP) can discontinue TKI treatment and maintain a therapy-free remission.

40 to enhance the possibility of discontinuing TKI treatment.

41 896 patients, 94.4% with documented TKI treatment, were followed for a median of 4.2 years.

42 om regained MMR within 4 months of full-dose TKI resumption (median time to recovery 77 days).

43 We analysed each TKI modality for response assessment and analysed surviv

44 nerally well-tolerated, and highly effective TKIs.

45 EGFR TKI efficiently targeted DeltaN566/DeltaN599-mutant-medi

46 e and evidence on therapy options after EGFR TKI treatment for patients with NSCLC, aiming to provide

47 hibit the spectrum of mutations driving EGFR TKI resistance in NSCLC.

48 ired resistance to the third-generation EGFR TKI AZD9291.

49 ed with osimertinib, a third-generation EGFR TKI, after previous treatment failure with one or more o

50 istance to first- and second-generation EGFR TKI, and recent clinical trials have documented their ef

51 of JNJ-61186372 and a third-generation EGFR TKI.

52 we found that EPHA2 is overexpressed in EGFR TKI-resistant tumor cells.

53 rmore, heregulin overexpression induced EGFR TKI resistance in NSCLC cells harbouring an activating E

54 tor receptor tyrosine kinase inhibitor (EGFR TKI) resistance induced by heregulin.

55 with acquired resistance to first-line EGFR TKI agents.

56 enhanced antiproliferative activity on EGFR TKI-resistant NSCLC.

57 udy, had shown resistance to a previous EGFR TKI, and had EGFR-activating mutations and acquired Thr7

58 rationale for a new strategy to target EGFR TKI-resistant GBM.

59 EGFR TKIs decrease both the mitogen-activated protein kinase

60 is resistant to all currently available EGFR TKIs.

61 All current EGFR TKIs target the ATP-site of the kinase, highlighting the

62 CLC might benefit from a combination of EGFR TKIs and CK1alpha inhibition to prevent acquired drug re

63 reatment failure with one or more other EGFR TKIs.

64 model systems of acquired resistance to EGFR TKIs, elevated expression of urokinase plasminogen activ

65 in vivo models restores sensitivity to EGFR TKIs.

66 that it can be used in combination with EGFR TKIs to treat a subset of heregulin-overexpressing NSCLC

67 th advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to identify somatic SNVs, small i

68 Patients who were included had acquired EGFR-TKI resistance and evidence of a common EGFR-sensitizing

69 plasma of NSCLC patients with acquired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in th

70 e a total of 119 patients with advanced EGFR-TKI-naive NSCLC and 15 EGFR-TKI-resistant patients to id

71 the SRS (n = 100), WBRT (n = 120), and EGFR-TKI (n = 131) cohorts was 46, 30, and 25 months, respect

72 Although the SRS and EGFR-TKI cohorts shared similar prognostic features, the WBRT

73 SRS followed by EGFR-TKI resulted in the longest OS and allowed patients to a

74 nal randomized trial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial prog

75 followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial

76 ients were treated with SRS followed by EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by

77 target IKBKE as a strategy to eradicate EGFR-TKI-resistant NSCLC cells.

78 tion of outcome from a third-generation EGFR-TKI, osimertinib.

79 might be an optional method to monitor EGFR-TKI resistance and to discover mechanisms of drug resist

80 EGFR-TKI, WBRT followed by EGFR-TKI, or EGFR-TKI followed by SRS or WBRT at intracranial progression.

81 Exclusion criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receiv

82 resistance mutation, failure to receive EGFR-TKI after WBRT/SRS, or insufficient follow-up.

83 brain metastases and have not received EGFR-TKI.

84 uired EGFR-TKI resistance than prior to EGFR-TKI therapy, and in the generated erlotinib-resistant HC

85 is demonstrated that the use of upfront EGFR-TKI, and deferral of radiotherapy, is associated with in

86 n criteria included prior EGFR-TKI use, EGFR-TKI resistance mutation, failure to receive EGFR-TKI aft

87 rial of SRS followed by EGFR-TKI versus EGFR-TKI followed by SRS at intracranial progression is urgen

88 lysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR exon 19 mutation, and

89 On multivariable analysis, SRS versus EGFR-TKI, WBRT versus EGFR-TKI, age, performance status, EGFR

90 nd in 46.7% (7/15) of the patients with EGFR-TKI-resistant NSCLC, suggesting that the NGS-based ctDNA

91 nisms mediating intrinsic resistance to EGFR-TKIs in CRC have not been fully characterized.

92 However, acquired resistance to EGFR-TKIs is widely detected across the world, and the exact

93 served in MMR and MR(4.5) is not an entirely TKI-mediated effect.

94 he transcription factor TWIST1 to facilitate TKI resistance, EMT, and cancer dissemination in a subse

95 Here, we have reported that the pan-FGFR TKI, NVP-BGJ398, reduces FGFR3 phosphorylation and corre

96 ]fludarabine was reduced by each of the five TKIs, and also caused a reduction in cell surface expres

97 ast in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein Bcl6

98 educed in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular d

99 evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT

100 ored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD)

101 tributes to maintenance of CML LSC following TKI treatment and that IL-1 blockade with IL-1RA enhance

102 ributes to preservation of CML LSC following TKI treatment.

103 e of the disease and effective therapies for TKI-refractory CML, or after progression to blast crisis

104 xpression and in BMP4 expression in LSC from TKI-resistant patients in comparison with diagnosis, whi

105 New-generation TKIs improve MMR but not the overall survival at 1 year

106 New-generation TKIs increased the rate of MMR at 1 year compared with i

107 molecular responses by the second-generation TKIs nilotinib, dasatinib, and bosutinib.

108 Data on second- and third-generation TKIs were limited.

109 However, TKI are not yet curative, because most patients retain l

110 However, TKIs are only efficacious in the chronic phase of the di

111 However, TKIs primarily target differentiated cells and do not el

112 Deeper mechanistic understanding may improve TKI combination therapies to better control the residual

113 we show that these elements are involved in TKI resistance.

114 port that BMP pathway alterations persist in TKI-resistant patients.

115 may serve as a useful therapeutic target in TKI-resistant tumors.

116 ere, recent data and concepts around VAEs in TKI-treated patients with CML are discussed, with specia

117 after failure of tyrosine kinase inhibitor (TKI) -based therapy.

118 d generation (2G)-tyrosine kinase inhibitor (TKI) is a multicenter observational study designed to ev

119 third-generation tyrosine kinase inhibitor (TKI) ponatinib shows activity against all common BCR-ABL

120 new mechanism of tyrosine kinase inhibitor (TKI) resistance, which is mediated through TKI-mediated

121 eased response to tyrosine kinase inhibitor (TKI) therapy and adverse survival.

122 (CML) patients on tyrosine kinase inhibitor (TKI) therapy and may promote treatment-free remission (T

123 Tyrosine-kinase inhibitor (TKI) therapy for human cancers is not curative, and rela

124 h CML may receive tyrosine kinase inhibitor (TKI) therapy for many decades, and are exposed to TKIs d

125 Although tyrosine kinase inhibitor (TKI) therapy has improved clinical outcome, most ALL pat

126 Tyrosine kinase inhibitor (TKI) therapy has led to substantial improvements in surv

127 iscontinuation of tyrosine kinase inhibitor (TKI) therapy is feasible for some patients with chronic

128 are sensitive to tyrosine kinase inhibitor (TKI) therapy, but resistance invariably develops, common

129 n the response to tyrosine kinase inhibitor (TKI) therapy, we analyzed if IFNgamma modulates BCL6 exp

130 86 of 90 received tyrosine kinase inhibitor (TKI) therapy.

131 years, the use of tyrosine kinase inhibitor (TKI) to counteract FGFR3 hyperactivity has yet to be eva

132 Tyrosine kinase inhibitor (TKI) treatment of chronic myeloid leukemia (CML) has lim

133 wing conventional tyrosine kinase inhibitor (TKI) treatment.

134 , another BCR-ABL tyrosine kinase inhibitor (TKI) used in patients with CML.

135 d with gefitinib (tyrosine kinase inhibitor (TKI)) and surface functionalized with cetuximab-siRNA co

136 sylate, the first tyrosine kinase inhibitor (TKI).

137 l sensitivity to tyrosine kinase inhibitors (TKI) - a common drug used for restoring the function of

138 BCR-ABL specific tyrosine kinase inhibitors (TKI) changed the outcome of chronic myeloid leukemia (CM

139 ML) with BCR-ABL tyrosine kinase inhibitors (TKI) fails to eliminate leukemia stem cells (LSC).

140 kinase-3 (FLT3) tyrosine kinase inhibitors (TKI) have been tested extensively to limited benefit in

141 ll-molecule EGFR tyrosine kinase inhibitors (TKI) have failed to yield durable clinical benefit.

142 ed with BCR-ABL1 tyrosine kinase inhibitors (TKI) in combination with chemotherapy.

143 Antiangiogenic tyrosine kinase inhibitors (TKI) that target VEGF receptor-2 (VEGFR2) have not been

144 tients with EGFR tyrosine kinase inhibitors (TKI), all patients eventually acquire resistance to thes

145 ome resistant to tyrosine kinase inhibitors (TKI), often through second-site mutations in EGFR (T790M

146 t-selective EGFR tyrosine kinase inhibitors (TKI), such as osimertinib, are active agents for the tre

147 effects of EGFR tyrosine kinase inhibitors (TKI).

148 atment with EGFR tyrosine kinase inhibitors (TKI).

149 and adherence to tyrosine kinase inhibitors (TKIs) among Medicare beneficiaries with chronic myeloid

150 ed resistance to tyrosine kinase inhibitors (TKIs) and cytotoxic drugs in AML.

151 Tyrosine kinase inhibitors (TKIs) are anticancer drugs that may be co-administered w

152 EGFR tyrosine-kinase inhibitors (TKIs) are given as a primary therapy for advanced patien

153 receptor (EGFR) tyrosine kinase inhibitors (TKIs) are standard treatments for advanced non-small-cel

154 receptor (EGFR)-tyrosine kinase inhibitors (TKIs) are treatment options for brain metastases in pati

155 Tyrosine kinase inhibitors (TKIs) are used in the clinical management of hematologic

156 small molecular tyrosine kinase inhibitors (TKIs) by concurrently stimulating EGFR gene transcriptio

157 Tyrosine kinase inhibitors (TKIs) directed against BCR-ABL1, the product of the Phil

158 (EGFR)-directed tyrosine kinase inhibitors (TKIs) gefitinib, erlotinib and afatinib are approved tre

159 matic success of tyrosine kinase inhibitors (TKIs) has led to the widespread perception that chronic

160 n c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival.

161 receptor (EGFR) tyrosine kinase inhibitors (TKIs) have demonstrated potent activity against TKI resi

162 Tyrosine kinase inhibitors (TKIs) have increased survival dramatically for patients

163 yeloid leukemia, tyrosine kinase inhibitors (TKIs) have turned a fatal disease into a manageable chro

164 BCR-ABL tyrosine kinase inhibitors (TKIs) imatinib and dasatinib inhibit fludarabine and cyt

165 therapy based on tyrosine kinase inhibitors (TKIs) is highly effective in inducing remission but not

166 Tyrosine kinase inhibitors (TKIs) of the EGF receptor (EGFR) have provided a signifi

167 sessment between tyrosine kinase inhibitors (TKIs) sensitive and resistant patient populations.

168 Although tyrosine kinase inhibitors (TKIs) that target the kinase activity of BCR-ABL1 have t

169 h may compliment tyrosine kinase inhibitors (TKIs) to eradicate LSC in chronic phase (CP) chronic mye

170 resistant to ALK tyrosine kinase inhibitors (TKIs) underwent apoptosis upon drug withdrawal as a cons

171 FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical

172 transporters and tyrosine kinase inhibitors (TKIs), which has uncovered widespread phosphotyrosine-me

173 sitivity to EGFR tyrosine kinase inhibitors (TKIs).

174 t promising EGFR tyrosine kinase inhibitors (TKIs).

175 receptor (EGFR) tyrosine-kinase inhibitors (TKIs).

176 rapies including tyrosine kinase inhibitors (TKIs).

177 th a low dose of tyrosine kinase inhibitors (TKIs).

178 d other anti-ALK tyrosine kinase inhibitors (TKIs).

179 are treated with tyrosine kinase inhibitors (TKIs).

180 (BCL2), and many tyrosine kinase inhibitors (TKIs).

181 ing therapy with tyrosine kinase inhibitors (TKIs).

182 s were significantly more likely to initiate TKIs.

183 ed with CML from 2007 to 2011, 68% initiated TKI treatment within 180 days after diagnosis.

184 of Medicare beneficiaries with CML initiated TKI therapy within 6 months of diagnosis.

185 Interestingly, TKIs modulated the chemokine receptor repertoire of immu

186 INTERPRETATION: TKI de-escalation is safe for most patients with excelle

187 y to at least one second-generation or later TKI or were intolerant to second-generation or later TKI

188 ere intolerant to second-generation or later TKIs and intolerant or refractory to imatinib.

189 Depending on choice of first line TKI, approximately 30% of CML CP cases show suboptimal r

190 These findings show that lower TKI doses might maintain responses in these patients, im

191 The identification of the known MET TKIs, glesatinib and foretinib, as negative modulators o

192 etastases and had previously had two or more TKI treatments fail.

193 28 (52%) patients had received two or more TKIs, and 39 (72%) patients had CNS metastases.

194 -63); for those who had received two or more TKIs, the proportion of patients with an objective respo

195 Moreover, TKIs reduced the expression of CXCR3 (in NK cells) and C

196 The most TKI-insensitive cells of the LSC compartment can be capt

197 Imatinib mesylate and new TKIs along with allogeneic stem cell transplantation and

198 tem cell assays, we showed that ACF, but not TKIs, targets the stem cell potential of CML cells, incl

199 d drug resistance, with approximately 50% of TKI-resistance caused by kinase domain mutations and the

200 In the absence of TKI, knocking down the oncogene dephosphorylated ERK, an

201 In the absence of TKI, the nanoparticle showed minimal toxicity suggesting

202 BCR-ABL1 undetectable following cessation of TKI therapy, n = 13).

203 reatment, responded well to a combination of TKI with anti-KIT antibodies or to anti-KIT toxin conjug

204 ide a framework for follow-on development of TKI binding modulators.

205 blockade with IL-1RA enhances elimination of TKI-treated CML LSC.

206 The loss of TKI sensitivity was most pronounced in patient samples h

207 bit higher BMP4 levels in the bone marrow of TKI-resistant patients.

208 Traditionally, mechanisms of TKI resistance have been viewed under a dichotomous lens

209 faceted, genetically heterogeneous nature of TKI resistance, which evolves dynamically with changes i

210 In the presence of TKI, GAB1-SHP2 dissociation occurs, leading to cell deat

211 EPHA2 in the maintenance of cell survival of TKI-resistant, EGFR-mutant lung cancer and indicate that

212 expression levels determine the threshold of TKI efficacy, such that growth-factor-induced expression

213 nderstanding the biological underpinnings of TKI resistance is key to the successful development of f

214 ho stopped therapy after at least 3 years of TKI treatment and in molecular response 4.5 (MR4.5) with

215 Our results suggest that combination of TKIs with BCL6 and MCL1 inhibitors may potentially lead

216 hat CML LSCs are resistant to the effects of TKIs and persist in all patients on long-term therapy, w

217 are to investigate the inhibitory effects of TKIs on UDP-glucuronosyltransferase (UGT) activities, an

218 tter interpreting the off-target efficacy of TKIs in tumors and to envisaging strategies aimed at fac

219 cohort of CML patients treated in the era of TKIs.

220 ients with CML treated by new generations of TKIs and provide an overall assessment of the clinical b

221 performance score >/= 90, and no history of TKIs before development of brain metastases were associa

222 Importantly, also in the presence of TKIs, the M2 immunosuppressive polarization was reverted

223 ng rationale for investigation of the use of TKIs in combination with tigecycline to treat patients w

224 omplications associated with lifelong use of TKIs.

225 es in CML patients at diagnosis (n = 21), on TKI (imatinib, nilotinib, dasatinib) before achieving ma

226 ost MMR on de-escalation and regained MMR on TKI resumption.

227 T cells persisted in pre-MMR CML patients on TKI.

228 riate analysis, prior suboptimal response or TKI resistance was the only baseline factor associated w

229 Tumor cells are TKI-sensitive or TKI-refractory, exhibit intrinsic or acquired resistance

230 .0007), but was unrelated to previous TKI or TKI therapy duration.

231 who develop resistance to imatinib and other TKIs used to treat this disease.

232 t combining HER-family inhibitors with other TKIs such as dasatinib may have therapeutic advantages i

233 37; p=0.0007), but was unrelated to previous TKI or TKI therapy duration.

234 emia in first chronic phase who had received TKI for 3 years or more and were either in stable MR4 (B

235 patients in complete cytogenetic remission, TKI-resistant LSC and progenitors display high levels of

236 selective, and brain-penetrant ALK and ROS1 TKI with preclinical activity against most known resista

237 We selected TKIs given their effectiveness and strong indication for

238 ther that third-generation DM EGFR-selective TKIs alter JM structure via allostery to restore the con

239 combining MTOR inhibitors and FGFR-specific TKIs.

240 Participants received half their standard TKI dose (imatinib 200 mg daily, dasatinib 50 mg daily,

241 d that loss of MR4.5 3 months after stopping TKI was predictive of failure to maintain MMR later on.

242 strate differences in response to subsequent TKI treatment between distinct subpopulations.

243 ts pathological hallmarks of ACH and support TKIs as a potential therapeutic approach for ACH.

244 -body) can be combined with VEGFR2-targeting TKIs (sunitinib or regorafenib) to successfully treat po

245 stable deep molecular response on long-term TKI therapy.

246 the basis of these findings we propose that TKIs, an important and rapidly expanding class of therap

247 In the absence of EGF the TKI-resistant EGFR mutant (L858R/T790M) had a higher deg

248 ll survival were similar irrespective of the TKI used.

249 rylation at Y1068, Y1086, and Y1173 than the TKI-sensitive EGFR.

250 rsely, NK cells were highly resistant to the TKI cytotoxic effect, were properly activated by immunos

251 ating EGFR mutation but was resistant to the TKI gefitinib.

252 ymal transition (EMT) has been linked to the TKI resistance in lung adenocarcinoma.

253 L CD34(+) cells, and in combination with the TKI nilotinib (NIL) significantly enhanced inhibition of

254 e-establish remission after restarting their TKI therapy.

255 Mechanistic studies showed that these TKIs inhibit the Src family kinase Yes1, which was found

256 The following three TKIs have been approved for the management of advanced d

257 (TKI) resistance, which is mediated through TKI-mediated priming of mesenchymal stem cells (MSCs) in

258 n and a TIE2 tyrosine kinase inhibitor (TIE2-TKI) for their effects on murine VM expansion and for th

259 Rapamycin prevented VM growth, while TIE2-TKI had no effect.

260 hanisms of intrinsic signaling adaptation to TKI treatment that are associated with an incomplete res

261 ng cancer cells would sensitize the cells to TKI drugs and offers an efficient therapy for treating c

262 ed EGFR-mutated lung adenocarcinoma cells to TKI.

263 regression to assess time from diagnosis to TKI initiation.

264 h numbers of monocytes died upon exposure to TKI concentrations similar to those achieved in patients

265 e knockdown; subsequently, sensitizing it to TKI.

266 OS and DUSP1 confers intrinsic resistance to TKI therapy in a wide-ranging set of leukemias, and migh

267 However, most patients develop resistance to TKI through BCR-ABL1-dependent and -independent mechanis

268 ly reduced at a higher extent in response to TKI therapy compared with subfractions displaying primit

269 Response to TKI therapy was similar for patients with CCA/Ph(-) and

270 abnormalities showed a marginal response to TKI treatment, and no patients achieved a long-term sust

271 ributed across subpopulations in response to TKI treatment.

272 or most patients with excellent responses to TKI therapy, and is associated with improvement in sympt

273 d that prolonged exposure of cancer cells to TKIs give rise to small populations of "drug tolerant pe

274 therapy for many decades, and are exposed to TKIs during a period of active growth, morbidities in ch

275 ldren as a way to avoid lifelong exposure to TKIs and their associated adverse effects.

276 ) ALL who had relapsed or were refractory to TKIs.

277 F in sensitive cells conferred resistance to TKIs and induced EMT, increasing migratory and invasive

278 However, acquired resistance to TKIs is a significant clinical problem in CML, and TKI t

279 s known, some patients develop resistance to TKIs, and the mechanisms mediating intrinsic resistance

280 nd patients eventually develop resistance to TKIs.

281 and M2 macrophages were highly resistant to TKIs and maintained their phenotypic and functional char

282 signaling network increased sensitivities to TKIs in K-Ras mutant cells in which EGFR knockdown inhib

283 lls was sufficient to improve sensitivity to TKIs and cytotoxic drugs.

284 novel strategy to restore the sensitivity to TKIs.

285 osphoproteome' with unique susceptibility to TKIs.

286 ies, in particular effective agents to treat TKI-refractory disease.

287 n, were inhibited by several clinically used TKIs.

288 tients with chronic-phase CML across various TKIs.

289 -CML treated on clinical trials with various TKIs.

290 ination with VEGF-A blockers (but not VEGFR2 TKIs) in resected breast cancer; in combination with VEG

291 cancer; and as single agents or with VEGFR2 TKIs in resected colorectal cancer.

292 ed breast cancer; in combination with VEGFR2 TKIs in resected kidney cancer; and as single agents or

293 Importantly, the combination of IL-1RA with TKI resulted in significantly greater inhibition of CML

294 ent of immature chronic phase CML cells with TKI alone, or in combination with interferon-alpha, resu

295 low dose radiation (LDR) in combination with TKI therapy overcome chemo-resistance.

296 greater inhibition of CML LSC compared with TKI alone.

297 LL patients relapse following treatment with TKI due to the development of resistance.

298 platform of "operational cure" for CML with TKIs and immunotherapies.

299 or an IGF-1R inhibitor, in combination with TKIs (Figure 5A-B).

300 prevent CML relapse and, in combination with TKIs, enhance induction of remission.