ライフサイエンスコーパス: CRPC

1 CRPC is a complex, multifaceted and heterogeneous malady

2 metastatic (n = 139) or metastatic (n = 257) CRPC were randomly assigned to enzalutamide 160 mg per d

3 ts were prospectively enrolled (9 HNPC and 8 CRPC); 16 had CIM evidence of new or progressive metasta

4 ta-catenin pathway will prove effective as a CRPC treatment remains unknown.

5 AR levels and leads to tumor regression in a CRPC mouse xenograft model.

6 of PSA in LNCaP-AKR1C3 cells as a model of a CRPC cell line.

7 that knockdown of PLZF expression promotes a CRPC and enzalutamide-resistant phenotype in prostate ca

8 Thus, TRX1 is an actionable CRPC therapeutic target through its protection against A

9 astration-resistant prostate adenocarcinoma (CRPC) to neuroendocrine prostate cancer (NEPC) has emerg

10 y characterized as prostate adenocarcinomas (CRPC-Adeno) and neuroendocrine prostate cancer (CRPC-NE)

11 ients treated with these agents for advanced CRPC generally relapse within a year and AR appears to b

12 Some success against CRPC has been achieved by drugs that target AR signaling

13 pe pathway for aberrant AR re-activation and CRPC growth in the milieu of low androgen.

14 t of differences between prostate cancer and CRPC at the level of the transcriptome.

15 6 in both cultured prostate cancer cells and CRPC xenograft tumors.

16 for treatment of both androgen-dependent and CRPC.

17 with 61 equivocal) overall, in both HNPC and CRPC patients.

18 regulated in a subset of CRPC cell lines and CRPC patient tumors.

19 3K signaling and promotes PCa metastasis and CRPC development.

20 d with higher Gleason score, metastasis, and CRPC progression.

21 rapeutic TRIM24 targeting in SPOP mutant and CRPC patients.

22 anisms by which EZH2 is regulated in PCa and CRPC remain elusive.

23 n regulating AR signaling transformation and CRPC progression remain unknown.

24 significantly impairs the tumorigenicity and CRPC development.

25 netic differences between CRPC-NE tumors and CRPC-Adeno, and also designated samples of CRPC-Adeno wi

26 mising candidates for further development as CRPC therapeutics.

27 with clinical features of AR independence as CRPC-NE, suggesting that epigenetic modifiers may play a

28 vealed marked epigenetic differences between CRPC-NE tumors and CRPC-Adeno, and also designated sampl

29 isrupted this negative feedback loop in both CRPC and enzalutamide-resistant prostate cancer cells.

30 oneal carcinomatosis from colorectal cancer (CRPC) is still a matter of debate.

31 ses to castration resistant prostate cancer (CRPC) after the androgen deprivation therapy.

32 riving castration-resistant prostate cancer (CRPC) are not clearly understood.

33 static castration-resistant prostate cancer (CRPC) before and after chemotherapy.

34 C) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and ci

35 vival, castration-resistant prostate cancer (CRPC) cells are eventually able to escape available horm

36 ell as castration-resistant prostate cancer (CRPC) cells in vitro and in vivo.

37 ity in castration-resistant prostate cancer (CRPC) cells is driven by increased CDK1-mediated S81 pho

38 revise castration-resistant prostate cancer (CRPC) clinical trial recommendations to succeed those fr

39 Castration-resistant prostate cancer (CRPC) continues to be a major clinical problem and the m

40 Castration-resistant prostate cancer (CRPC) continues to pose a significant clinical challenge

41 e termed castrate-resistant prostate cancer (CRPC) develops.

42 static castration-resistant prostate cancer (CRPC) frequently develop therapeutic resistance to taxan

43 astatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity.

44 iew of castration-resistant prostate cancer (CRPC) has changed dramatically in the last several years

45 static castration-resistant prostate cancer (CRPC) invariably succumb to the disease.

46 ent of castration-resistant prostate cancer (CRPC) is associated with the activation of intratumoral

47 Castration-resistant prostate cancer (CRPC) is characterized by a shift in androgen receptor (

48 ype of castration-resistant prostate cancer (CRPC) is generally caused by augmented signaling from th

49 Castration-resistant prostate cancer (CRPC) is the lethal form of prostate cancer, and more th

50 Castration-resistant prostate cancer (CRPC) is the main challenge for prostate cancer treatmen

51 static castration-resistant prostate cancer (CRPC) is the primary cause of prostate cancer-specific m

52 als in castration-resistant prostate cancer (CRPC) need new clinical end points that are valid surrog

53 orm of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate can

54 static castration-resistant prostate cancer (CRPC) patients obtained at rapid autopsy to evaluate div

55 Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the

56 moting castration-resistant prostate cancer (CRPC) survival and growth even after androgen deprivatio

57 a) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor

58 static castration-resistant prostate cancer (CRPC) tissue biomarker-guided therapeutic trial (NCT0091

59 urable castration-resistant prostate cancer (CRPC) via compensatory mechanisms including resurgence o

60 n with castration-resistant prostate cancer (CRPC) was associated with primary resistance to enzaluta

61 n with castration-resistant prostate cancer (CRPC) who range from being asymptomatic with only bioche

62 t CaP (castration-resistant prostate cancer (CRPC)) cell lines.

63 Castration-resistance prostate cancer (CRPC), also known as hormone-refractory prostate cancer

64 eating castration-resistant prostate cancer (CRPC), but tumours frequently become drug resistant via

65 lethal castration-resistant prostate cancer (CRPC), even when patients are treated with potent second

66 evelop castration-resistant prostate cancer (CRPC), for which there is no effective treatment and is

67 ent of castration-resistant prostate cancer (CRPC), including resistance to the new generation of hig

68 ase is castration-resistant prostate cancer (CRPC), where patients no longer respond to medical or su

69 ses to castration-resistant prostate cancer (CRPC), which is still reliant on androgen receptor (AR)

70 asion in castrate-resistant prostate cancer (CRPC), yet mechanisms of regulation remain largely unkno

71 human castration-resistant prostate cancer (CRPC).

72 ly, in castration resistant prostate cancer (CRPC).

73 C) and castration-resistant prostate cancer (CRPC).

74 ers of castration resistant prostate cancer (CRPC).

75 es for castration-resistant prostate cancer (CRPC).

76 ration resistant (advanced) prostate cancer (CRPC).

77 static castration-resistant prostate cancer (CRPC).

78 ays in castration-resistant prostate cancer (CRPC).

79 ers of castration-resistant prostate cancer (CRPC).

80 urable castration-resistant prostate cancer (CRPC).

81 tastatic castrate-resistant prostate cancer (CRPC).

82 udy in castration-resistant prostate cancer (CRPC).

83 lethal castration-resistant prostate cancer (CRPC).

84 /CT in castration-resistant prostate cancer (CRPC).

85 t into castration-resistant prostate cancer (CRPC).

86 static castration-resistant prostate cancer (CRPC).

87 stage of castrate-resistant prostate cancer (CRPC).

88 s with castration-resistant prostate cancer (CRPC).

89 ent of castration-resistant prostate cancer (CRPC).

90 static castration-resistant prostate cancer (CRPC).

91 urable castration-resistant prostate cancer (CRPC).

92 ion to castration-resistant prostate cancer (CRPC).

93 urable castration-resistant prostate cancer (CRPC).

94 nce of castration-resistant prostate cancer (CRPC).

95 apy in castration-resistant prostate cancer (CRPC); however, mechanisms underlying the clinical activ

96 C-Adeno) and neuroendocrine prostate cancer (CRPC-NE); analysis of biopsy samples from the same indiv

97 Castration-resistant prostate cancers (CRPC) that arise after the failure of androgen-blocking

98 Consistent with its activation in clinical CRPC, tumors driven by Notch1 intracellular domain in co

99 exhibits the key characteristics of clinical CRPC and thus provides a valuable tool for identifying d

100 demonstrated that, similarly to the clinical CRPC, orthotopically grown castration-resistant VCaP (CR

101 Identical to clinical CRPC, the expression levels of the full-length AR (twofo

102 this purpose, we constructed a comprehensive CRPC regulatory network by integrating multiple pathways

103 tate cancers, with implications for defining CRPC biomarkers and new therapeutic interventions.

104 cancer progression and in androgen-deprived CRPC cells, suggesting that CRPC possesses an enhanced d

105 3 levels and cell death in androgen-deprived CRPC cells.

106 d the AR cistrome in a PCa cell line-derived CRPC model using integrated bioinformatical analyses.

107 reatment of mice xenografted with ARV-driven CRPC tumors with a drug-like small-molecule Sigma1 inhib

108 88-H4/WDR5/MLL2/AR epigenetic circuit drives CRPC and is necessary for maintenance of the malignant s

109 SD1-mediated epigenetic reprogramming drives CRPC, and they offer a mechanistic rationale for its the

110 ied AR variants, including AR-V7 that drives CRPC progression.

111 lated lipid biosynthetic pathways in driving CRPC progression, and suggest that ADTs may be therapeut

112 PLZF loss enhances CRPC tumor growth in a xenograft model.

113 hese results indicate that UGT2B17 expedites CRPC progression by enhancing ligand-independent AR sign

114 lesterol synthesis in AR variants-expressing CRPC cell line and xenograft models markedly reduces tum

115 elopment of novel therapeutic approaches for CRPC.

116 iosynthetic pathway (HBP) to be critical for CRPC.

117 Clinical Context The treatment goal for CRPC is palliation.

118 multaneous targets of multiple pathways, for CRPC.

119 endent manner in CRPC cells and required for CRPC cell proliferation under androgen-deprived conditio

120 of these transcripts that were specific for CRPC, we defined a novel lncRNA termed PCAT5 as a regula

121 may be a promising therapeutic strategy for CRPC treatment.

122 to AR inhibition and therapeutic target for CRPC treatment.

123 t REST is a potential therapeutic target for CRPC.

124 the optimal order of hormonal therapies for CRPC beyond second-line treatment.

125 The need for effective treatments for CRPC is a pressing concern, especially due to limited du

126 re are no AR variant-specific treatments for CRPC.

127 unctions in CRPC offers new knowledge on how CRPC progresses and acquires chemoresistance during tumo

128 The mechanism underlying how CRPC gains resistance toward hormone depletion and other

129 e we show that AR-signalling-competent human CRPC cell lines are preferentially sensitive to bromodom

130 Combination treatment of human CRPC xenografts with cabazitaxel and enzalutamide revers

131 y inhibits efficiently tumor growth of human CRPC xenografts.

132 tly inhibited PI3K-Akt signaling and impeded CRPC progression.

133 In CRPC tumors, UGT2B17 expression was associated positivel

134 In CRPC, AKR1C3 is implicated in drug resistance, and enzal

135 ndrogen receptor variants that accumulate in CRPC cells utilize distinct pathways of nuclear import t

136 ly expressed and transcriptionally active in CRPC, and indicated that steroids from the adrenal gland

137 ctural alterations in driving AR activity in CRPC, mechanisms of action for abiraterone and enzalutam

138 ntinib has clinically meaningful activity in CRPC.

139 nical trials showing a survival advantage in CRPC for treatment with abiraterone (inhibitor of the en

140 AR cistrome analyses in CRPC cells have identified a large number of AR target g

141 Analyses in CRPC cells reveal that the TRIM24 bromodomain and the AR

142 ore efficacious than direct AR antagonism in CRPC xenograft mouse models.

143 ivity, which may be exploited to drive AR in CRPC.

144 important mechanism of resistance to ARSI in CRPC.

145 ical role for the SET-PP2A signaling axis in CRPC progression and hormone resistant disease.

146 nergies on imaging studies of the AR-axis in CRPC, using (18)F-FDG, (18)F-16beta-fluoro-5alpha-dihydr

147 serve as a treatment selection biomarker in CRPC.

148 delineate treatment response of dasatinib in CRPC bone metastases with borderline correlation with PF

149 1) is found to be significantly decreased in CRPC compared with localized prostate cancer (PCa).

150 n receptor (AR) remains a critical driver in CRPC, understanding the determinants of its transcriptio

151 which antiandrogens mediate their effects in CRPC.

152 may contribute to their clinical efficacy in CRPC.

153 key residues were significantly enriched in CRPC tumors after incorporation of phosphoproteomic data

154 r, the compound loss of which is enriched in CRPC.

155 uggesting that AD-resistant AR expression in CRPC induces redox vulnerability.

156 nstitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted

157 rent elevation of Skp2 and Ezh2 was found in CRPC tumors of Pten/Trp53 mutant mice, and expression le

158 ist stabilization and oncogenic functions in CRPC offers new knowledge on how CRPC progresses and acq

159 dy supports a critical role for GABPalpha in CRPC and reveals potential targets for therapeutic inter

160 Genetic loss-of-function of GNPNAT1 in CRPC-like cells increases proliferation and aggressivene

161 te the therapeutic value of targeting HBP in CRPC.

162 Menin expression is higher in CRPC than in both hormone-naive prostate cancer and beni

163 ve identified potential pathways involved in CRPC development, the drivers of CRPC remain largely und

164 nes, and differentially activated kinases in CRPC tissues to synthesize a robust signaling network co

165 together with the finding of genetic loss in CRPC implicates PLZF inactivation as a mechanism promoti

166 by the AR in a ligand-independent manner in CRPC cells and required for CRPC cell proliferation unde

167 ophagy is an important survival mechanism in CRPC.

168 ling in androgen-sensitive tumors but not in CRPC.

169 eatment (ADT) and is highly overexpressed in CRPC tumors compared with hormone-naive prostate cancer

170 er, the determinants of AR overexpression in CRPC are poorly defined.

171 sults establish ROR-gamma as a key player in CRPC by acting upstream of AR and as a potential therape

172 ppressing AR-mediated disease progression in CRPC.

173 ls, although the effect is more prominent in CRPC.

174 er, which was associated with loss of RB1 in CRPC.

175 and other pathways typically represented in CRPC gene signatures.

176 ivity, undergoes epigenetic reprogramming in CRPC.

177 lthough AR activity is generally restored in CRPC despite the castrate level of androgens, it is uncl

178 apeutic strategies targeting AR signaling in CRPC.

179 section between Polycomb and AR signaling in CRPC.

180 rtant drivers of persistent AR signalling in CRPC.

181 edback mechanism of androgenic signalling in CRPC.

182 Phase III clinical studies in CRPC patients are scheduled to begin in early 2015.

183 n and represents a new therapeutic target in CRPC.

184 l, we defined an important role of TXNDC5 in CRPC and further investigations are needed to screen TXN

185 vated genes are significantly upregulated in CRPC.

186 xpression of a broad array of AR variants in CRPC.

187 that can predict recurrence and drive lethal CRPC is critical.

188 TXDNC5-mediated CRPC growth can be fully abolished by AR inhibition, sug

189 tested in both nonmetastatic and metastatic CRPC populations.

190 Strikingly, primary and metastatic CRPC showed robust synergistic responses when immune che

191 zed high-risk prostate cancer and metastatic CRPC, but not benign prostate tissues or low/intermediat

192 -222 was highly expressed in bone metastatic CRPC tumor specimens.

193 Men with bone metastatic CRPC underwent (18)F-fluoride PET before and 12 weeks af

194 is a promising approach to combat metastatic CRPC by targeting Twist and CSCs.

195 lecular imaging of the AR-axis in metastatic CRPC (mCRPC) and discuss our personal experience with th

196 els are significantly elevated in metastatic CRPC patients compared with hormone naive patients, rais

197 is overexpressed and amplified in metastatic CRPC tumors, and that ROR-gamma drives AR expression in

198 f activated signaling pathways in metastatic CRPC while providing an integrative, pathway-based refer

199 in patients with nonmetastatic or metastatic CRPC.

200 o treat men with nonmetastatic or metastatic CRPC.

201 alternative pathways in promoting metastatic CRPC and may represent a new therapeutic target for adva

202 se prostate cancer to progress to metastatic CRPC.

203 spectively enrolled patients with metastatic CRPC initiating taxane chemotherapy (docetaxel or cabazi

204 on of AR-V7 in CTCs from men with metastatic CRPC is not associated with primary resistance to taxane

205 prednisone alone in patients with metastatic CRPC previously treated with docetaxel.

206 alysis of a cohort of 34 men with metastatic CRPC treated with docetaxel chemotherapy reveals that ER

207 rednisone alone for patients with metastatic CRPC.

208 and reduced AR and AR-V7 levels to mitigate CRPC tumor growth.

209 utamide were effective in bicalutamide-naive CRPC patients, but not in bicalutamide-pretreated ones.

210 cond-line hormonal therapy for nonmetastatic CRPC nor provided specific guidance with regard to the c

211 on trials are also underway in nonmetastatic CRPC.

212 progression for trials in the nonmetastatic CRPC state.

213 be considered in patients with nonmetastatic CRPC at high risk for metastatic disease (rapid prostate

214 he molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotype

215 AB1A, which could mediate the development of CRPC phenotype in multiple prostate cancer cell lines.

216 rovide the foundation for the development of CRPC therapeutic strategies that would be highly efficie

217 with metastatic PCa, mediates development of CRPC.

218 -deficient mice prevented the development of CRPC.

219 involved in CRPC development, the drivers of CRPC remain largely undefined.

220 Evaluation of CRPC cell lines identified resistant vs sensitive in vit

221 ymptomatic with only biochemical evidence of CRPC to having documented metastases but minimal symptom

222 d in prostate cancer), impedes the growth of CRPC cells to a greater extent than their androgen-depen

223 s and blocked androgen-independent growth of CRPC cells.

224 rg effect) is also an early manifestation of CRPC transformation.

225 , AIL blocks tumour growth and metastasis of CRPC.

226 ole of Aurora A kinase on AR-Vs in models of CRPC and show depletion of Aurora A reduces AR-V target

227 ally improved efficacy in cellular models of CRPC as compared with BET inhibition.

228 expression in in vitro and in vivo models of CRPC is associated with decreased sensitivity to taxanes

229 inhibitory activity in preclinical models of CRPC.

230 The pathophysiology of CRPC is clearly multifactorial, but most often, androgen

231 verses the castration-resistant phenotype of CRPC cells, significantly inhibiting tumor formation und

232 2 (Skp2) in the formation and progression of CRPC.

233 ase, ELOVL7, also leads to the regression of CRPC xenograft tumors.

234 RV expression and restores responsiveness of CRPC to anti-androgen therapy.

235 d CRPC-Adeno, and also designated samples of CRPC-Adeno with clinical features of AR independence as

236 f different pathways, a system-wide study of CRPC regulation is necessary.

237 ence that SLPI is upregulated in a subset of CRPC cell lines and CRPC patient tumors.

238 in from enzymatic cleavage or suppression of CRPC cell apoptosis independent of anti-protease activit

239 e, AR-V-driven proliferation and survival of CRPC cells is markedly reduced.

240 plications as it can prolong the survival of CRPC patients by restoring the tumors to once again resp

241 ecular alterations occurring in one third of CRPC-stage tumours.

242 Treatment of CRPC cells with enzalutamide or HIF-1alpha inhibition at

243 tant therapeutic advance in the treatment of CRPC.

244 s a potential candidate for the treatment of CRPC.

245 seful in patient-individualized treatment of CRPC.

246 ctors that drives the high tumorigenicity of CRPC cells.

247 that are associated with prostate cancer or CRPC.

248 s performed in the context of either HNPC or CRPC.

249 develop metastatic castration-resistant PC (CRPC) invariably succumb to the disease.

250 ith progression to castration-resistant PCa (CRPC) and high levels of Bag-1L in primary PCa associate

251 ogen-dependent and castration-resistant PCa (CRPC) cells, although the effect is more prominent in CR

252 but its effect on castration-resistant PCa (CRPC) is limited.

253 AR retargeting in castration-resistant PCa (CRPC) with next-generation endocrine therapies abiratero

254 PCa progresses to castration-resistant PCa (CRPC), making the development of efficient therapies cha

255 e androgen levels (castration-resistant PCa, CRPC).

256 s significantly overexpressed in AR-positive CRPC samples carrying amplification of AR gene and/or ex

257 has functional significance, as it promotes CRPC cell survival and growth after androgen withdrawal

258 reated prostate cancer and locally recurrent CRPC.

259 We revealed that Skp2 regulates CRPC through Twist-mediated oncogenic functions includin

260 -independent (AIPC) or castration-resistant (CRPC) forms.

261 f prostate cancer to a castration-resistant (CRPC) state.

262 am kinase-regulating Mnk1/2, also sensitized CRPC cells to RAD001+bicalutamide.

263 PCa models, and they effectively sensitized CRPC tumors to enzalutamide, without overt toxicity, in

264 mediated knockdown (k/d) of eIF4E-sensitized CRPC cells to RAD001+bicalutamide, whereas eIF4E overexp

265 ctivating Skp2 synergistically re-sensitized CRPC cells toward chemotherapies such as paclitaxel or d

266 r a new therapeutic approach for sensitizing CRPC to ADT and radiation.

267 ress to a lethal castration-resistant state (CRPC).

268 More recent studies showed that CRPC cells had increased expression of enzymes mediating

269 ndrogen-deprived CRPC cells, suggesting that CRPC possesses an enhanced dependency on TRX1.

270 a mechanism promoting ADT resistance and the CRPC phenotype.

271 t the AR cistrome is largely retained in the CRPC stage.

272 222 in LNCaP promoted the development of the CRPC phenotype.

273 ch in turn may mediate the transition to the CRPC phenotype.

274 iRs) in the transition of prostate cancer to CRPC.

275 dual androgens makes a major contribution to CRPC, and led to the recent Food and Drug Administration

276 lite UDP-N-acetylglucosamine (UDP-GlcNAc) to CRPC-like cells significantly decreases cell proliferati

277 hough several biologic mechanisms leading to CRPC development and their relative frequencies have bee

278 TRIM24 protein increases from primary PC to CRPC, and both TRIM24 protein levels and the AR/TRIM24 g

279 cal mechanism by which the PCa progresses to CRPC.

280 Progression to CRPC after androgen ablation therapy is predominantly dr

281 tion, invasion, and xenograft progression to CRPC after prolonged androgen deprivation.

282 ed and reactivated during the progression to CRPC, and increased level of lipid synthesis is associat

283 a promising new therapeutic option to treat CRPC.

284 et genes may provide new approaches to treat CRPC.

285 the initial efficacy of taxanes in treating CRPC, all patients ultimately fail due to the developmen

286 r, intensifying the need to fully understand CRPC pathophysiology.

287 Arr2 knockdown inhibits the in vitro CRPC cell proliferation, prostasphere growth and invasio

288 Intratumoral hypoxia is also associated with CRPC progression and treatment resistance.

289 neuroendocrine (NE) cells is associated with CRPC.

290 One hundred seventy-one men with CRPC were enrolled.

291 Provisional Clinical Opinion For men with CRPC, a castrate state should be maintained indefinitely

292 ed, double-blind, phase II study of men with CRPC.

293 prostate-specific antigen in a patient with CRPC, and another study showed seviteronel's direct effe

294 tion in predicting outcomes in patients with CRPC receiving first- and second-line NHT and, to the be

295 We prospectively enrolled 202 patients with CRPC starting abiraterone or enzalutamide and investigat

296 has been recently approved in patients with CRPC with bone metastases.

297 le to customize treatments for patients with CRPC, which might improve outcomes.

298 peutic approaches to treat PCa patients with CRPC.

299 CT imaging was performed on 30 patients with CRPC.

300 ial as a therapeutic target in patients with CRPC.