ライフサイエンスコーパス: MEK

1 MEK, a central component of the Ras/MAPK cascade, is mut

2 MEK/ERK and NFkappaB inhibitors were used to assess the

3 MEK/ERK inhibition also drove oligodendrocyte formation

4 dabrafenib, a BRAF inhibitor; trametinib, a MEK inhibitor or SCH772984, an ERK inhibitor.

5 Treatment of the clusters with trametinib, a MEK inhibitor, had only a modest effect on these culture

6 The approach of using a MEK inhibitor before radioiodine treatment could readily

7 th rescue of the anomalous phenotype using a MEK inhibitor.

8 tion of iodine uptake after treatment with a MEK inhibitor alone and in combination with a PI3'K inhi

9 ther therapeutic options, was treated with a MEK inhibitor and underwent a transient clinical respons

10 f tumor burden when mice were treated with a MEK inhibitor before radioiodine administration.

11 00E) PIK3CA(H1047R) mice were treated with a MEK inhibitor followed by radioiodine treatment, and tum

12 combination treatment of palbociclib with a MEK inhibitor in pancreatic cancer PDX models upregulate

13 ubsequent therapy of the lead proband with a MEK inhibitor led to dramatic clinical improvement, with

14 mors when administered in combination with a MEK inhibitor, providing a new mechanism through which s

15 symporter transcription when treated with a MEK or BRAF(V600E) inhibitor alone and in combination wi

16 -induced organ wasting, we observed aberrant MEK activation in both tumors and host tissues of flies

17 Galphai2-coupled receptor subunit activated MEK/ERK and PI3K, resulting in aggressive, immune-suppre

18 the major vault protein (MVP) and activates MEK through MVP-enhancing B-RAF and MEK interaction.

19 ing a serine-threonine kinase that activates MEK(3,4).

20 The rosette then activates MEK signals that induce lumenogenesis and drive progress

21 lation of ELK1 at Ser 383 through activating MEK/ERK signaling.

22 eam effector PI3K but instead require active MEK (mitogen-activated protein kinase kinase 1) signalin

23 However, the organoids surviving after MEK inhibition maintain cellular heterogeneity.

24 chanistically, we observed that single-agent MEK inhibition led to compensatory activation of resista

25 Cells that acquire resistance to an MEK-PI3K inhibitor combination treatment still respond t

26 nhibition of heat shock protein (Hsp)-90 and MEK was found to produce robust suppression of tumor gro

27 results in activation of STAT, PI3K/AKT, and MEK/ERK signaling.

28 Calcium channel blockade and MEK inhibition could prevent some of the disease charact

29 gful therapeutic targets outside of BRAF and MEK are undefined.

30 K pathway by combined inhibition of BRAF and MEK has increased overall survival in advanced BRAF-muta

31 Small molecule inhibitors of BRAF and MEK have proven effective at inhibiting tumor growth in

32 enesis and potentiate inhibitors of BRAF and MEK in cells with BRAF V600 mutations.

33 a cell lines chronically exposed to BRAF and MEK inhibition, with consequent increased resistance to

34 BRAF and MEK inhibitor combinations have been approved for use in

35 treatment of melanoma patients with BRAF and MEK inhibitors (MEKi) activated tumor NF-kappaB activity

36 BRAF-mutant melanomas treated with BRAF and MEK inhibitors almost invariably develop resistance that

37 eatment of metastatic melanoma with BRAF and MEK inhibitors has improved survival, but the emergence

38 BRAF and MEK inhibitors reduce metastatic burden for patients wit

39 ma cells that tolerates exposure to BRAF and MEK inhibitors undergoes a reversible remodelling of mRN

40 from highly effective therapy with BRAF and MEK inhibitors.

41 trials of combination therapy with BRAF and MEK inhibitors.

42 duced by the combined inhibition of BRAF and MEK(1).

43 ance, combination therapy targeting BRAF and MEK, a downstream signaling target of BRAF in the MAPK p

44 o interfered with the host cellular cAMP and MEK/ERK cascade pathways.

45 al vulnerability to coinhibition of COX2 and MEK.

46 ation with the BRAF inhibitor dabrafenib and MEK inhibitor trametinib.

47 antineoplastic agents that inhibit EGFR and MEK is frequently limited by cutaneous adverse reactions

48 cells to survive dual inhibition of EGFR and MEK.

49 down-regulated during response to B-Raf and MEK inhibition and was again up-regulated on drug resist

50 and is associated with response to B-Raf and MEK inhibition.

51 ctivates MEK through MVP-enhancing B-RAF and MEK interaction.

52 mor aggression, chemotherapy resistance, and MEK inhibitor resistance in vivo.

53 es, tumor growth, chemotherapy response, and MEK inhibitor response.

54 ests that upfront dual inhibition of TRK and MEK may delay time to progression in cancer types prone

55 ve to targeted inhibitors of BRAF(V600E) and MEK, responding in a manner consistent with human BRAF(V

56 Consequently, combined WNT and MEK inhibition supports rosette-like stem cells, a self-

57 ombination therapies targeting both YAP1 and MEK.

58 splantation, cladribine and cytarabine, anti-MEK agent, vinblastine, etc) used for maintenance could

59 Here, we use the clinically approved MEK inhibitor Trametinib to investigate its potential us

60 esistance against cancer medications such as MEK and BRAF inhibitors.

61 s with clonal inflammatory disorders bearing MEK and RUNX1 mutations such as histiocytoses and myeloi

62 co platform to attempt to distinguish benign MEK mutations from those that are functional and, theref

63 Accordingly, BET/MEK inhibitors suppress pre-RC proteins in cycling cells

64 2, which confers sensitivity to combined BET/MEK inhibitors in xenograft and PDX models.

65 leagues reveal an unexpected synergy between MEK inhibitors and immune checkpoint blockade in non-sma

66 de, there is no apparent benefit of blocking MEK compared to targeting PI3K.

67 or Slug, a process that is dependent on both MEK/ERK signaling and ATF4.

68 fferentiation antigens, as well as to BRAF + MEK inhibitors.

69 tream signaling partners such as KRAS, BRAF, MEK, and AKT.

70 ma cells to multiple stresses including BRAF-MEK inhibition.

71 teins could predict drug sensitivity to BRAF-MEK concurrent inhibition in cells carrying BRAF mutatio

72 BRAF/MEK inhibition is a standard of care for patients with B

73 BRAF/MEK-targeted therapies have effects on the tumor microen

74 g resistance, and ABL1/2 drive BRAF and BRAF/MEK inhibitor resistance by inducing reactivation of MEK

75 ile those three regimens or combination BRAF/MEK inhibitor therapy with dabrafenib/trametinib, encora

76 of p53 inhibitor at the commencement of BRAF/MEK inhibitor therapy.

77 ect responses to targeted inhibitors of BRAF/MEK or DNA damaging agents.

78 elevated DNFA gene expression after the BRAF/MEK signaling pathway is blocked (e.g. by BRAF inhibitor

79 ent is currently based on targeting the BRAF/MEK/ERK signaling pathway and immune checkpoints.

80 treatment with either targeted therapy (BRAF/MEK inhibitors) or immunotherapy, during recovery time o

81 notype and sensitizes melanoma cells to BRAF/MEK inhibition.

82 on, and resensitizes resistant cells to BRAF/MEK inhibitors, whereas expression of constitutively act

83 reated with either a BRAF inhibitor (BRAFi), MEK inhibitor (MEKi), or the combination were included.

84 Finally, a bortezomib (BTZ)/MEK inhibitor combination showed enhanced activity in vi

85 ty, and class II MHC mismatch and blocked by MEK/ERK and NFkappaB inhibition.

86 el to dissect dual phosphorylation of ERK by MEK, a kinase that is mutated in a large number of human

87 In cells resistant to trametinib, a clinical MEK inhibitor (MEKi), a similar coclustering of NRas and

88 ular matrix contact, and found that combined MEK and integrin beta1 inhibition bypassed trametinib re

89 s predictive markers of response to combined MEK and p110beta/PI3K inhibition.

90 s sufficient to cause resistance to combined MEK/CDK inhibition and to replace genetic depletion of o

91 lnerabilities in HNSCC and support combining MEK and EGFR inhibitors to enhance clinical efficacy in

92 ticity crosstalk mediated by NMDAR-dependent MEK/ERK signaling.

93 les and molecular mechanisms of differential MEK activation in tumor-induced host wasting.

94 . exposure to radiation or TMZ, neither does MEK inhibition block their effectiveness.

95 -Ras expression, and that K-Ras(G12V)-driven MEK/ERK activity is necessary for this lethality.

96 uppressor in neuroblastoma and suggests dual MEK and YAP inhibition as a potential therapeutic strate

97 Inhibiting the KRAS effector MEK and its upstream activators EGFR and MET demonstrate

98 vein (vn) ligand to trigger autonomous Egfr/MEK-induced tumor growth and produce the PDGF- and VEGF-

99 ollowing EGFR TKI treatment by combined EGFR/MEK inhibition uncovers cells that survive by entering a

100 all deplete dormant cells by enhancing EGFR/MEK inhibition-induced apoptosis.

101 ation of EGFR ligands and activation of EGFR/MEK/ERK pathway.

102 ng SOX2 promoted cell migration via the EGFR/MEK/ERK pathway.

103 ism for acneiform skin toxicity wherein EGFR/MEK inhibitors cooperate with the skin commensal Cutibac

104 In addition to elucidating why EGFR/MEK inhibitor-induced rashes are often pustular and foll

105 extracellular-signal-regulated kinase (ERK) (MEK) 1/2, which has been approved for treatment of metas

106 )/extracellular signal-related kinase (ERK) (MEK) biology and our observation that 6-OH-BDE-47 is str

107 evated FAM83A expression maintains essential MEK/ERK survival signalling, preventing cell death in pa

108 s can be recapitulated without affecting FGF-MEK signalling or global DNA methylation.

109 ar differentiation stimuli, particularly FGF-MEK signalling.

110 RG, a transcriptional factor downstream from MEK/ERK, binds to the promoter region of VE-cadherin (ch

111 n of exogenous cAMP and dominant active FST7 MEK kinase.

112 electrical activity, pre-synaptic functions, MEK-ERK signaling, and axonal guidance.

113 t the ground state ESCs cultured with GSK3-, MEK-inhibitors and LIF (2iL) display higher ribosome den

114 rgeted therapies against the oncogenic BRAF->MEK->ERK pathway and immune checkpoint inhibitors for th

115 tumor suppressor that inhibits the RAS->RAF->MEK->ERK pathway and is one of the most frequently inact

116 Here we show that inhibition of KRAS->RAF->MEK->ERK signaling elicits autophagy, a process of cellu

117 Downstream of KRAS, the RAF->MEK->ERK signaling pathway plays a central role in pancr

118 Strikingly, host MEK suppression alone is sufficient to abolish the wasti

119 urage the clinical development of HSP90(i) + MEK(i) combination therapy and highlight the power of cl

120 The combination of HSP90(i) + MEK(i) was also active in vitro in established human PDA

121 etion, specifically TAK1, IKKbeta, IkBalpha, MEK 1/2, ERK 1/2, and p38.

122 cal resistance phenomenon, well-described in MEK-ERK-driven solid tumors, in which drug-target overex

123 75) is often upregulated and mislocalized in MEK/ERK-deregulated tumors.

124 gain-of-function, destabilizing mutations in MEK.

125 tion increased mitochondrial permeability in MEK-ERK-deregulated cells to an extent that triggered ce

126 er, studies of novel single agents including MEK inhibitors (MEKi) have demonstrated limited efficacy

127 Mechanistically, increased MEK-ERK signaling activity and mortalin function converg

128 , including SRC, FES, YES1, and BLK, induced MEK-independent ERK activation in melanoma A375 cells.

129 Combined JAK/MEK inhibition suppressed MEK/ERK activation in Jak2V617

130 the efficacy of JAK2 inhibition and dual JAK/MEK inhibition provides an opportunity for improved ther

131 The MAPK/ERK kinase MEK is a shared effector of the frequent cancer drivers

132 ibition of BRAF or the downstream MAP kinase MEK is highly effective in treating BRAF-mutant melanoma

133 irectly phosphorylates both MAPK/ERK kinase (MEK) and MAPK kinase 7 (MKK7).

134 phorylated ERK (dpERK) from MAPK/ERK kinase (MEK), a kinase that phosphorylates ERK, and other cytopl

135 N12 at cell membranes in an MAPK/ERK kinase (MEK)/ERK-dependent manner.

136 osphorylation of downstream MAPK/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK).

137 or mitogen-activated protein kinase kinase (MEK) (trametinib) and with STAT3 knockdown.

138 the mitogen-activated protein kinase kinase (MEK) 1/2 inhibitor trametinib independent of their BRAF

139 and mitogen-activated protein kinase kinase (MEK) inhibition were explored.

140 the mitogen-activated protein kinase kinase (MEK) inhibitor trametinib, the mTOR complex 1 (mTORC1) i

141 and mitogen-activated protein kinase kinase (MEK) inhibitors induces a high initial response rate in

142 nct mitogen-activated protein kinase kinase (MEK) inhibitors yielded synergistic growth inhibition wh

143 MAPK)-extracellular regulated kinase kinase (MEK), and MAPK-activated protein kinase-2 (MK2).

144 ations leading to activation of MAPK kinase (MEK) and extracellular signal-regulated kinase 1/2 signa

145 Pharmacologic RAF or MAPK kinase (MEK) inhibitors decreased proteasome activity, and sensi

146 downstream mitogen-activated protein kinase (MEK-ERK) signaling to alter cell mechanics and enhance m

147 mors with abnormal activation of the kinases MEK and ERK.

148 ve mitogen-activated protein kinase kinases (MEKs/MKKs) and some variants of the NLRP1 inflammasome s

149 Moreover, trametinib binds KSR-MEK but disrupts the related RAF-MEK complex through a m

150 ma cells carrying NRas mutations but lacking MEK mutations.

151 tine import with an xCT transporter-lowering MEK inhibitor, in combination with statins, caused profo

152 However, many MEK inhibitors are limited owing to on-target toxicities

153 In iPSC-derived microglia, MEK inhibition increased cell surface TREM2 only modestl

154 uced stem cell propagation by regulating MVP/MEK signaling axis independent of the classic Ras pathwa

155 he same effect, suggesting that noncanonical MEK signaling regulates TREM2 trafficking.

156 66, and previously named RO5126766), a novel MEK-pan-RAF inhibitor, has shown antitumour activity acr

157 , providing a quantitative method to observe MEK inhibition in vivo.

158 nclusion: This study confirms the ability of MEK inhibition to induce iodine uptake in in vitro and i

159 Depletion of MVP blocks the activation of MEK induced by B7-H3 and dramatically inhibits B7-H3 ind

160 1 signaling as well as via the activation of MEK/ERK.

161 del to show that the local administration of MEK and Akt inhibitors limits the lgCMN proliferative po

162 We show that a combination of MEK and CDK4/6 inhibitors that target KRAS-directed onco

163 Finally, a combination of MEK and MET inhibition demonstrated activity in models o

164 ctal cancer cell lines with a combination of MEK- and PI3K-inhibitors, we observe a synergistic inhib

165 derstanding of the structure and function of MEK within physiological complexes could provide a templ

166 herapy and to widen the therapeutic index of MEK inhibitors.

167 Furthermore, inhibition of MEK activity by trametinib showed similar effects.

168 Combined inhibition of MEK and p110beta/PI3K reduced mouse tumor cell growth in

169 Therapeutic inhibition of MEK and p110beta/PI3K using selumetinib (AZD6244, ARRY-1

170 Combined inhibition of MEK and SHP2 is effective in models of NF1-MPNST, both t

171 Small-molecule inhibition of MEK led to increased cell surface expression of TNF rece

172 The latter was ablated by inhibition of MEK, but not p38, confirming a role for ERK1/2 in regula

173 2019;25:628-640) reported that inhibition of MEK-ERK signaling in KRAS-mutated cancers induced autoph

174 itigated in part by concurrent inhibition of MEK.

175 emical screening revealed that inhibition of MEK/ERK signaling overcame the HIF1a-mediated block in o

176 PDAC cells were incubated with inhibitors of MEK (trametinib) or extracellular signal-regulated kinas

177 this was a general activity of inhibitors of MEK and ERK kinases.

178 Inhibition or knockdown of MEK, ERK or RSK1 caused impaired vRNP export and reduced

179 The complex clinical landscape of MEK mutations illustrates the need for improved methods

180 king substitutions in the activation loop of MEK, its catalytic activity is predicted to be substanti

181 interrogated the well-described mechanism of MEK/ERK pathway inhibitor addiction in solid tumors and

182 -1 induction, known resistance mechanisms of MEK inhibition.

183 Here, we set out to identify mechanisms of MEK inhibitor resistance in pancreatic cancer.

184 Downstream signaling pathways of MEK (p38(MAPK) and ERK1/2(MAPK)) were then examined, and

185 way by downregulating the phosphorylation of MEK and extracellular signal-regulated kinase (ERK).

186 bolite similarly impaired phosphorylation of MEK/ERK1/2 and activity-induced transcription of a neuro

187 S signaling escape the selective pressure of MEK inhibition via YAP1-mediated transcriptional reprogr

188 bitor resistance by inducing reactivation of MEK/ERK/MYC signaling.

189 We investigated the role of MEK/ERK signaling in MPN cell survival in the setting of

190 Here we report X-ray crystal structures of MEK bound to the scaffold KSR (kinase suppressor of RAS)

191 in pediatric diseases, including the use of MEK inhibitors in plexiform neurofibromas associated wit

192 s stimulus reliant and retains dependence on MEK activity.

193 as small molecule inhibitors of BRAF and/or MEK for the subgroup of patients with BRAF(V600) mutatio

194 st potential susceptibility to CDK4/6 and/or MEK inhibitors.

195 psed and refractory LCH treated with BRAF or MEK inhibitors, although potential for this strategy to

196 ated through enhanced DNA repair, as EGFR or MEK/ERK inhibitors delayed DNA damage resolution.

197 The combination of EGFR TKI and FGFR1 or MEK inhibitors may offer an attractive therapeutic strat

198 ination of EGFR TKI with FGFR1 inhibitors or MEK inhibitors reverses this resistance.

199 tive therapeutic strategy in B-Raf-mutant or MEK-ERK-driven tumors.

200 hile, the expression levels of P65, p-P65, p-MEK and p-IkappaB-alpha were inhibited dose-dependently.

201 resistance has emerged through "paradoxical MEK/ERK signaling" where transactivation of one protomer

202 Consequently, PDO325901 (MEK inhibitor), CHIR99021 (GSK-3beta inhibitor) and Dasa

203 or targeting such patients with PI/RAF or PI/MEK inhibitor combinations.

204 view the clinical data for various BRAF plus MEK combination regimens in three cancer types with unde

205 st-line combination treatment with BRAF plus MEK inhibitors and immune checkpoint therapy in BRAF(V60

206 eceiving treatment with BRAF inhibitors plus MEK inhibitors.

207 Addition of a potent MEK inhibitor that blocks MAPK signaling brings each onc

208 ligand to non-autonomously activate host Pvr/MEK signaling and wasting.

209 that highly intermittent schedules of a RAF-MEK inhibitor has antitumour activity across various can

210 ter DNAJ-PKAc/Hsp70 sub-complexes with a RAF-MEK-ERK kinase module.

211 mours or multiple myeloma harbouring RAS-RAF-MEK pathway mutations.

212 ours and multiple myeloma harbouring RAS-RAF-MEK pathway mutations.

213 ed with hyperactive signaling of the RAS-RAF-MEK pathway.

214 The RAS-RAF-MEK-ERK signaling axis is frequently activated in human

215 b binds KSR-MEK but disrupts the related RAF-MEK complex through a mechanism that exploits evolutiona

216 Signal transduction through the RAF-MEK-ERK pathway, the first described mitogen-associated

217 uding constitutive signaling through the RAF-MEK-ERK proproliferative pathway as well as the PI3K-AKT

218 lect distinct feedback mechanisms in the Raf-MEK-ERK signaling network, with the receptors themselves

219 -6258 is a novel and potent strategy for RAF/MEK inhibitor-resistant melanoma and potentially other t

220 - and SOS1-inhibition markedly inhibited Raf/MEK/ERK and PI3K/AKT signaling.

221 e/extracellular signal-regulated kinase (Raf/MEK/ERK) pathway is functionally linked to nuclear expor

222 Ras/Raf/MEK/ERK (Ras-ERK) signaling has been implicated in the e

223 The RAS/RAF/MEK/ERK pathway promotes gliogenesis but the kinetic rol

224 mitoylated N-Ras mutant protein, reduced Raf/MEK/ERK signaling, and alterations in hematopoietic stem

225 allows for reversible activation of the RAF/MEK/ERK pathway via plasma membrane recruitment of RAF1

226 Patients with melanoma resistant to RAF/MEK inhibitors (RMi) are frequently resistant to other t

227 activity across various cancers with RAF-RAS-MEK pathway mutations, and that this inhibitor is tolera

228 The oncogenic activation of the RAS-MEK pathway suppresses CASZ1 expression in ERMS.

229 together, loss of CASZ1 activity, due to RAS-MEK signaling or genetic alteration, impairs ERMS differ

230 direct transforming effect via constant RAS/MEK/ERK signaling, an inflammation-related effect of KRA

231 ling a mechanism whereby a neurofibromin/Ras/MEK pathway regulates a critical CIN developmental miles

232 S-GAP) NF1 drives aberrant activation of RAS/MEK/ERK signaling and other effector pathways in the maj

233 udies showed that BOL effectively sensitized MEK inhibitors through repression of p-STAT3 and MCL-1 i

234 versed upon MEK inhibitor addition, and SERD/MEK inhibitor combinations induce tumor regression.

235 Combined JAK/MEK inhibition suppressed MEK/ERK activation in Jak2V617F and MPLW515L mice with i

236 basement membrane mimetic Matrigel survived MEK inhibition, while the cells in the interior layers u

237 ng checkpoint inhibitors and drugs targeting MEK or PI3K, can be used in combination with CDK4/6 inhi

238 the chimeric protein DeltaRaf-1:ER and that MEK-ERK-sensitive regulation of the peptide-binding doma

239 WISP1 activates AKT Ser/Thr kinase and that MEK/ERK signaling pathways shift melanoma cells from pro

240 Here, we show that MEK and RAF inhibitors do not suppress levels of SOX10 p

241 ns are reversible in zebrafish suggests that MEK inhibition may represent a promising therapeutic tre

242 lays an indispensable role in activating the MEK/ERK pathway to drive tumorigenesis.

243 Although the MEK Inhibitor in Low-Grade Serous Ovarian Cancer Study d

244 requires temporal treatment of BMP4 and the MEK inhibitor PD0325901 for 48 h on protocol day 30.

245 ing of the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib improves progression-free survi

246 ceived the BRAF inhibitor dabrafenib and the MEK inhibitor trametinib together with the PD-1-blocking

247 ossible cross talk between eIF2alpha and the MEK/ERK pathway in neuropathic nerves.SIGNIFICANCE STATE

248 which trametinib directly engages KSR at the MEK interface.

249 (+) and PV(+) CINs, which was rescued by the MEK inhibitor SL327, revealing a mechanism whereby a neu

250 a positive feed-forward loop mediated by the MEK/ERK-activated AP-1 transcription factors, JUNB and F

251 toxicity, at least in part, by impairing the MEK-ERK axis of MAPK signal transduction.

252 y, we discovered that several kinases in the MEK/ERK2 pathway destabilize Shank3 and that genetic del

253 gh activation of MAPK kinases, including the MEK/ERK pathway as well as several transcription factors

254 inical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clini

255 ls the prototypical allosteric pocket of the MEK inhibitor, thereby affecting binding and kinetics, i

256 F activation and subsequent elevation of the MEK/ERK signaling.

257 evels, but rather a dramatic increase of the MEK/ERK/c-Jun pathway accompanied by a reduction in expr

258 p27 via inhibition of SKP2 and targeting the MEK/ERK pathway enhanced the cytostatic effect of CDK4/6

259 We subsequently demonstrated that the MEK inhibitor PD325901 administered peripherally prior t

260 tors (CHILP), at least partially through the MEK-dependent pathway.

261 lanoma xenografts that were resistant to the MEK inhibitor (MEKi) PD0325901 in vivo.

262 the BCL2-family inhibitor navitoclax to the MEK-PI3K inhibitor regimen improves the synergistic inte

263 d antitumor activity in combination with the MEK inhibitor trametinib in patient-derived xenograft mo

264 amma agonist rosiglitazone combined with the MEK inhibitor trametinib.

265 ng to dissect the mechanisms that make these MEK mutants hyperactive.

266 DH1 transcription and glutaminolysis through MEK/ERK pathway, providing new insight into oncogenic al

267 in adult melanomas and could be amenable to MEK inhibition.

268 providing a critical strategic complement to MEK inhibitor therapy.

269 hose tested, only IFN-gamma priming prior to MEK inhibitor treatment resulted in greater TREM2 recrui

270 mutant KRAS dependency and recalcitrance to MEK inhibition.

271 Importantly, the mechanisms of resistance to MEK and PI3K inhibitors observed, MEK1/2 mutation or los

272 etiglue, which limits adaptive resistance to MEK inhibition by enhancing interfacial binding.

273 vercome intrinsic and acquired resistance to MEK inhibition in colorectal cancer.

274 ibiting intrinsic and acquired resistance to MEK inhibition.

275 underlie adaptive and acquired resistance to MEK inhibitor (MEKi).

276 clinical utility in overcoming resistance to MEK inhibitor regimes; however, we find a recurrent acti

277 eted evaluation of the signaling response to MEK inhibition, we have identified global activation of

278 iminished aggressive behavior in response to MEK inhibition.

279 ovel explanation for the limited response to MEK inhibitors in KRAS-mutant colorectal cancer, known f

280 and that they are consequently responsive to MEK inhibition.

281 ia phenotype, making cells more sensitive to MEK inhibitor-induced TREM2 recruitment.

282 Lung cancer cells are rendered sensitive to MEK inhibitors by TNFalpha and IFNgamma, providing a str

283 ells expressing R183W were less sensitive to MEK inhibitors.

284 f RAS as a mechanism to limit sensitivity to MEK inhibition.

285 the MAPK/ERK pathway predicts sensitivity to MEK inhibition.

286 ression and morphogenesis pivots from WNT to MEK signals.

287 dabrafenib (BRAF inhibitor) and trametinib (MEK inhibitor) for patients with BRAF-mutated melanoma (

288 e substantially lower than that of wild-type MEK that has been phosphorylated at these residues.

289 Primary HCE were treated with EGF +/- U0126 (MEK inhibitor) and assayed for TGF-betaRII expression.

290 However, upon MEK inhibition some cell populations appear to favour ce

291 SERD resistance, which can be reversed upon MEK inhibitor addition, and SERD/MEK inhibitor combinati

292 d MAPKs MKK-3/6 and p38MAPK or to upregulate MEK-1/2 and ERK-1/2 in BALB/c-derived peritoneal macroph

293 sitivity and sensitized the cells to various MEK inhibitors.

294 KSR (kinase suppressor of RAS) with various MEK inhibitors, including the clinical drug trametinib.

295 Specifically, whereas MEK-ERK activity increased mitochondrial permeability by

296 rapeutics, such as checkpoint blockers, with MEK inhibitor therapy for lung cancer.See related commen

297 be used either alone or in combination with MEK inhibitors for the treatment of human CRC.

298 structure of human BRAF(KD) in complex with MEK and the ATP analog AMP-PCP, revealing interactions b

299 e embryonic stem cells (mESCs) cultured with MEK/ERK and GSK3beta (2i) inhibitors transition to groun

300 the plasticity of an interface pocket within MEK sub-complexes and have implications for the design o