ライフサイエンスコーパス: CRPC

1 CRPC is a complex, multifaceted and heterogeneous malady

2 CRPC tumors develop resistance to new-generation antiand

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

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

5 with metastatic prostate adenocarcinoma and CRPC-NE, we identified CRPC-NE features detectable in th

6 ation therapies to treat prostate cancer and CRPC.Significance: Merging mathematical modeling with ex

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

8 ied miRs that modulate AR activity in PC and CRPC, via novel mechanisms, and may represent novel PC t

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

10 significantly impairs the tumorigenicity and CRPC development.

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

12 d that selective FASN inhibition antagonizes CRPC growth through metabolic reprogramming and results

13 ARL/- CRPC expressed abundant AR mRNA despite diminished level

14 DDX3 protein was highly expressed in ARL/- CRPC, where it bound to AR mRNA.

15 y quantified DDX3 and AR expression in ARL/- CRPC.

16 DDX3 may be targetable for sensitizing ARL/- CRPC to AR-directed therapies.

17 AR-low/negative (ARL/-) CRPC subtypes have recently been characterized and canno

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

19 RNA level across multiple publicly available CRPC datasets.

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

21 D8 T cells and subsequent regression of bone CRPC and improves survival.

22 to elicit an anti-tumor response in the bone CRPC model despite an increase in the intra-tumoral CD4

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

24 sed in castration-resistant prostate cancer (CRPC) and NEPC, but its specific role is unknown.

25 lethal castration-resistant prostate cancer (CRPC) are poorly understood.

26 ent of castration-resistant prostate cancer (CRPC) as the oral administration of these drugs is large

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

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

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

30 ing of castration-resistant prostate cancer (CRPC) clinical trial target populations.

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

32 sed in castration-resistant prostate cancer (CRPC) from both human patients and a mouse xenograph mod

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

34 ent of castration-resistant prostate cancer (CRPC) in chemotherapy-naive as well as in patients previ

35 wth of castration-resistant prostate cancer (CRPC) in vitro and in vivo, and overexpression of ZBTB7A

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

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

38 Castration-resistant prostate cancer (CRPC) is defined by tumor microenvironment heterogeneity

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

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

41 ds the castration resistant prostate cancer (CRPC) patients' survival an extra 4.8 months, it might a

42 val in castration resistant prostate cancer (CRPC) patients.

43 s to a castration-resistant prostate cancer (CRPC) phenotype that accounts for virtually all prostate

44 ver of castration-resistant prostate cancer (CRPC) progression.

45 ndent to castrate-resistant prostate cancer (CRPC) remains a clinical challenge.

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

47 MET in castration-resistant prostate cancer (CRPC) specimens.

48 lethal castration-resistant prostate cancer (CRPC) stage.

49 Castration-resistant prostate cancer (CRPC) that has developed resistance to the new-generatio

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

51 so in castration-resistant prostate cancer (CRPC) tumors.

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

53 use of castration-resistant prostate cancer (CRPC) which invariably develops after anti-androgenic th

54 n with castration-resistant prostate cancer (CRPC) who have symptomatic bone metastases and no known

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

56 Castration-resistant prostate cancer (CRPC) with neuroendocrine differentiation (NED) is a let

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

58 ape of castration-resistant prostate cancer (CRPC), identifying actionable targets, and emerging resi

59 ant of castration-resistant prostate cancer (CRPC), is increasing in incidence with the widespread us

60 py, or castration-resistant prostate cancer (CRPC), is often accompanied by metastasis and is current

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

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

63 lethal castration-resistant prostate cancer (CRPC).

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

65 ion of castration-resistant prostate cancer (CRPC).

66 evelop castration-resistant prostate cancer (CRPC).

67 ies in castration-resistant prostate cancer (CRPC).

68 sis of castration-resistant prostate cancer (CRPC).

69 ion of castration-resistant prostate cancer (CRPC).

70 rapy for castrate-resistant prostate cancer (CRPC).

71 ion of castration-resistant prostate cancer (CRPC).

72 essive castration resistant prostate cancer (CRPC).

73 lethal castration-resistant prostate cancer (CRPC).

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

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

76 static castration-resistant prostate cancer (CRPC).

77 urable castration-resistant prostate cancer (CRPC).

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

79 urable castration-resistant prostate cancer (CRPC).

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

81 human castration-resistant prostate cancer (CRPC).

82 geting castration-resistant prostate cancer (CRPC).

83 esses to castrate-resistant prostate cancer (CRPC).

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

85 n with castration-resistant prostate cancer (CRPC).

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

87 on-resistant neuroendocrine prostate cancer (CRPC-NE).

88 ndent castration-resistant prostate cancers (CRPC), whose frequency is increasing, is also unknown.

89 n castration-resistant prostate cancer cell (CRPC) and spheroid models.

90 erlie expression of diverse AR-Vs in certain CRPC tumors, but post-transcriptional processes represen

91 NA classifier' that could robustly classify 'CRPC-NE' from 'CRPC-Adeno' cases.

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

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

94 Increased CHPT1 conferred CRPC resistance to Enz in vitro and in mice.

95 in clinical trials to overcome AR-dependent CRPC.

96 We show in ARv7-dependent CRPC models that ARv7 binds together with ARfl to repres

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

98 3 levels and cell death in androgen-deprived CRPC cells.

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

100 rm enzalutamide treatment of patient-derived CRPC xenografts.

101 biopsy tissues, and was capable of detecting CRPC-NE-associated epigenetic changes (e.g., hypermethyl

102 s relapse with castration-resistant disease (CRPC) when treated with anti-androgen therapy.

103 en in advanced 'castrate-resistant' disease (CRPC).

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

105 c opportunities for muscarinic-signal-driven CRPC progression by targeting the FAK-YAP signaling axis

106 ivo, IPI-9119 reduced growth of AR-V7-driven CRPC xenografts and human mCRPC-derived organoids and en

107 88-H4/WDR5/MLL2/AR epigenetic circuit drives CRPC and is necessary for maintenance of the malignant s

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

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

110 , which induced the immunosuppression during CRPC progression.

111 PSMA PET/CT is of value in early CRPC and should be included in the CRPC entry criteria o

112 igen (PSMA) PET/CT in the detection of early CRPC (prostate-specific antigen <= 3 ng/mL).

113 Detection of early CRPC facilitates disease-delaying therapies for local or

114 ethods: We identified 55 patients with early CRPC from our institutional database.

115 Enz resistance to further suppress the EnzR CRPC.

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

117 Such knowledge could facilitate CRPC tumour stratification and identify targets for more

118 s + PDX models with adenocarcinoma features (CRPC-adeno) vs those with neuroendocrine features (CRPC-

119 deno) vs those with neuroendocrine features (CRPC-NE).

120 gesting a potential therapeutic approach for CRPC and NEPC.

121 elopment of novel therapeutic approaches for CRPC.

122 ntified that nMET signaling requires ARF for CRPC growth in Pten/Trp53 conditional knockout mouse mod

123 tion, as a clinically relevant biomarker for CRPC.

124 Whether AR-V7 can be a driver for CRPC remains controversial as the oncogenic mechanism of

125 nerating AR-V7 and a contributing factor for CRPC, providing insight for mechanistic targeting of CRP

126 Clinical Context The treatment goal for CRPC is palliation.

127 uch, our work has important implications for CRPC progression and development of resistance to treatm

128 lled patients who had undergone PSMA PET for CRPC, had prostate-specific antigen values of at least 1

129 oved enzalutamide is commonly prescribed for CRPC which works by blocking androgen receptor function.

130 sitivity to enzalutamide and is required for CRPC growth in vitro and in vivo.

131 may be a promising therapeutic strategy for CRPC treatment.

132 t REST is a potential therapeutic target for CRPC.

133 e mechanisms hold as therapeutic targets for CRPC.

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

135 pICln may be explored as a novel therapy for CRPC treatment by suppressing expression of AR and AR sp

136 consuming ellagic acid during treatment for CRPC and indicate need for further research, but BRB con

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

138 liceosome as a therapeutic vulnerability for CRPC.

139 that could robustly classify 'CRPC-NE' from 'CRPC-Adeno' cases.

140 Furthermore, CRPC tumors in which Pten is lost are also resistant to

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

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

143 reatment for better suppression of the human CRPC progression.

144 te adenocarcinoma and CRPC-NE, we identified CRPC-NE features detectable in the circulation.

145 In CRPC, AR is often aberrantly activated independent of an

146 In CRPC, AR-V7 expression is predominantly (94% of cases) n

147 coding gene, PTK2 is frequently amplified in CRPC cases.

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

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

150 of posttranscriptional regulation for AR in CRPC.

151 itivity to AR-signaling inhibitors (ARSI) in CRPC xenografts in vivo.

152 ts provide insights into the role of ARv7 in CRPC and define a set of potential biomarkers for tumors

153 s associated with positive ARv7 detection in CRPC patients following Enz treatment.

154 which antiandrogens mediate their effects in CRPC.

155 may contribute to their clinical efficacy in CRPC.

156 Ellagic acid inhibited drug efflux in CRPC cells, but BRB extract and PCA did not.

157 Moreover, Trop2 is significantly elevated in CRPC and NEPC, drives prostate cancer growth, and induce

158 6beta1 and Bnip3 are selectively elevated in CRPC downstream of AR.

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

160 and enhanced the efficacy of enzalutamide in CRPC cells.

161 onal regulators that are highly expressed in CRPC and whose suppression, via both transcriptional or

162 ipt variants of the AR gene are expressed in CRPC cells and can be translated to produce AR variant (

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

164 ated with AR and AR-V7 protein expression in CRPC tissues and their expression was highly correlated

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

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

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

168 rapeutic potential of MAPK/ERK inhibitors in CRPC.

169 e specificity and the dependence of KDM3B in CRPC proliferation.

170 AR-FL and AR-Vs that is commonly observed in CRPC and suggests the utility of targeting c-Myc as an a

171 o cytoplasmic puncta with SG marker PABP1 in CRPC.

172 ling, indicated by SMAD2 phosphorylation, in CRPC as compared with primary tumors.

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

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

175 ivity, undergoes epigenetic reprogramming in CRPC.

176 PT1 expression and confers Enz resistance in CRPC, suggesting that SE-mediated expression of downstre

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

178 nal regulation of AR mRNA (messenger RNA) in CRPC.

179 y between AKT, NF-kappaB and AR signaling in CRPC, and the preclinical studies suggest that a novel r

180 section between Polycomb and AR signaling in CRPC.

181 ay contribute to persistent AR signalling in CRPC in the absence of circulating androgens.

182 edback mechanism of androgenic signalling in CRPC.

183 orrelated with a unique 59-gene signature in CRPC, including HOXB13, a critical coregulator of AR-V7

184 chanism by which AR drives tumor survival in CRPC to identify ways to overcome resistance to PI3K inh

185 However, the role of the immune system in CRPC development remains unclear.

186 n and represents a new therapeutic target in CRPC.

187 tant potentiation of enzalutamide therapy in CRPC patients.

188 epigenetic activator of AR transcription in CRPC, requiring cooperation with a methylosome subunit p

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

190 ulatory mechanism for expression of AR-Vs in CRPC.

191 molecular insights of the role of ZBTB7A in CRPC cells and demonstrates globally its critical role i

192 s are often tightly correlated in individual CRPC samples, yet our understanding of how their express

193 Initially CRPC remains dependent on androgen receptor (AR) signali

194 Interestingly, CRPC tumors continue to depend on hyperactive AR signali

195 of gene-expression data from 159 metastatic CRPC samples and 2142 primary prostate tumors showed tha

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

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

198 and transcriptional features from metastatic CRPC biopsies prior to treatment would be predictive of

199 n a retrospective cohort of human metastatic CRPC clinical samples + PDX models with adenocarcinoma f

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

201 wing HOXB13 depletion in multiple metastatic CRPC models.

202 y and accuracy especially for non-metastatic CRPC and should be implemented in future clinical trial

203 in patients with nonmetastatic or metastatic CRPC.

204 se prostate cancer to progress to metastatic CRPC.

205 eatment (160 mg/d) in 36 men with metastatic CRPC.

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

207 ounts for these effects, we treated multiple CRPC cell lines with the BET bromodomain inhibitor JQ1 a

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

209 ), in the development of AR pathway-negative CRPC, a form of the disease that has increased in incide

210 sitivity to PI3K inhibitors in Pten-negative CRPC.

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

212 s; of these, 6 of 10 (60%) had nonmetastatic CRPC on CI.

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

214 onducted deep phenotypic characterization of CRPC metastases and patient-derived xenograft (PDX) line

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

216 se a novel role of NTS in the development of CRPC with NED, and a possible strategy to prevent the on

217 The mechanism underlying development of CRPC with NED, however, remains largely uncharacterized.

218 The diagnosis of CRPC-NE currently relies on a metastatic tumor biopsy, w

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

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

221 r understanding of the molecular features of CRPC is now being translated into the clinic in the form

222 n of AR-V-target genes and reduces growth of CRPC cell lines suggesting a synthetic lethality relatio

223 AR-Vs are able to support growth of CRPC cells by promoting expression of AR target genes th

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

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

226 argeting PRMT5 or pICln suppressed growth of CRPC cells.

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

228 , AIL blocks tumour growth and metastasis of CRPC.

229 Preclinical study in a mouse model of CRPC suggests therapeutic potential by targeting lncRNA

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

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

232 nsin (NTS) in cell line and animal models of CRPC with NED.

233 GABA) shunt is upregulated with the onset of CRPC, via phosphorylation and activation of glutamate de

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

235 2 (Skp2) in the formation and progression of CRPC.

236 ent to effectively prevent the recurrence of CRPC.

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

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

239 inhibition blocks growth of a diverse set of CRPC cell models, including those that are AR-independen

240 have shown promise in preclinical studies of CRPC.

241 ases (SFKs), is overexpressed in a subset of CRPC.

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

243 and Bnip3 were found to promote survival of CRPC cells selectively on laminin through the induction

244 oviding insight for mechanistic targeting of CRPC.

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

246 tant therapeutic advance in the treatment of CRPC.

247 nhibitors could be an effective treatment of CRPC.

248 ation as lead compounds for the treatment of CRPC.

249 r, as a molecular target in the treatment of CRPC.See related article by Gao et al., p.

250 ctors that drives the high tumorigenicity of CRPC cells.

251 ancer (NEPC), a highly aggressive variant of CRPC.

252 s interact with docetaxel and cabazitaxel on CRPC cells in culture and implanted into nude mice.

253 of AR could be a viable strategy to overcome CRPC.

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

255 ion is frequent in castration-resistant PCa (CRPC) compared with hormone-sensitive PCa (HSPC) specime

256 eness and inhibits castration-resistant PCa (CRPC) in xenograft and autochthonous PCa models.

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

258 eventually develop castration-resistant PCa (CRPC).

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

260 eletion impairs lipid metabolism and reduces CRPC tumour growth, emphasizing the importance of DECR1

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

262 er (PC) progressed to castration resistance (CRPC) is a fatal disease.

263 at are abnormally activated in Enz-resistant CRPC cells and associated with enhanced transcription of

264 tylation (H3K27ac) ChIP-seq in Enz-resistant CRPC cells, we identified a group of super enhancers (SE

265 ions that help manage enzalutamide-resistant CRPC.

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

267 R1 knockout induces ER stress and sensitises CRPC cells to ferroptosis.

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

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

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

271 progresses to a castration-resistant state (CRPC).

272 ICT in the subcutaneous CRPC model significantly increases intra-tumoral T(h)1 s

273 ential by targeting lncRNA PCAT1 to suppress CRPC progression.

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

275 , the progression-free survival rate for the CRPC patients on antiandrogen therapies is only 8-19 mon

276 in early CRPC and should be included in the CRPC entry criteria of the European Association of Urolo

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

278 nificantly from localized prostate cancer to CRPC and further upon enzalutamide resistance.

279 an play a critical role in the conversion to CRPC.

280 ose in TP53 and RB1, during the evolution to CRPC.

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

282 ally relevant genetic alterations leading to CRPC may reveal potential vulnerabilities for cancer the

283 matically understand the immunity leading to CRPC progression and predict the optimal treatment strat

284 sion of lncRNA-PCAT1 is positively linked to CRPC progression.

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

286 et genes may provide new approaches to treat CRPC.

287 ical anti-NRG1/HER3 therapeutics in treating CRPC.

288 need to understand the mechanisms underlying CRPC progression and eventual treatment resistance.

289 le androgen-dependent disease to untreatable CRPC.

290 We utilized CRPC models to identify DDX3:AR mRNA complexes by RNA im

291 neuroendocrine (NE) cells is associated with CRPC.

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

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

294 proteins are being explored in patients with CRPC and metastatic bone disease.

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

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

297 tissue genomic alterations in patients with CRPC-NE compared with castration-resistant adenocarcinom

298 DNA was capable of identifying patients with CRPC-NE.

299 ial as a therapeutic target in patients with CRPC.

300 ibiting cell invasion in vitro and xenograft CRPC tumor growth and metastasis in vivo.