ライフサイエンスコーパス: PARP

1 PARP catalytic domains transfer the ADP-ribose moiety fr

2 PARP inhibition (PARPi) kills tumor cells defective in h

3 PARP inhibition is an effective treatment for patients w

4 PARP inhibitor treatment suppressed the immediate histon

5 PARP inhibitors are approved for treatment of cancers wi

6 PARP inhibitors have shown remarkable efficacy in the cl

7 PARP inhibitors increased the risk of myelodysplastic sy

8 PARP-1 and its enzymatic activity are key regulators of

9 PARP-1 binds to snoRNAs, which stimulate PARP-1 catalyti

10 PARP-1 was not cleaved but over-activated under AEBP1 do

11 PARPs comprise a family of 17 enzymes in humans, 16 of w

12 PARPs play an indispensable role in DNA damage repair an

13 Poly(ADP-ribose) polymerase 1 (PARP-1) is a nuclear enzyme involved in DNA repair and t

14 Inhibition of polyADP-ribose polymerase 1 (PARP-1) suppressed the nuclease-mediated collapse of the

15 mall molecule Poly(ADP-ribose) polymerase-1 (PARP) inhibitor, talazoparib led to increased DNA double

16 he success of poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to th

17 dependent on poly (ADP-ribose) polymerase-1 (PARP-1); a NAD(+)-consuming enzyme activated by strand b

18 s of tumor-infiltrating cells in dual PARP-1/PARP-2-deficiency host-mice revealed a global change in

19 We found that dual PARP-1/PARP-2-deficiency in T cells promotes tumor growth while

20 sed the embryonic lethality of dually PARP-1/PARP-2-deficient mice by using a PARP-1-deficient mouse

21 Hence, targeting ALC1 alone or as a PARP inhibitor sensitizer could be employed to augment e

22 ARP inhibitor off-trial, three had entered a PARP inhibitor trial and 5 were receiving platinum-based

23 first evidence for cellular lethality from a PARP-1-targeted Auger emitter, calling for further inves

24 RBM14 is recruited to DNA damage sites in a PARP- and RNA polymerase II (RNAPII)-dependent manner.

25 ollection nine BRCAm patients had received a PARP inhibitor off-trial, three had entered a PARP inhib

26 ian latency period since first exposure to a PARP inhibitor was 17.8 months (8.4-29.2; n=58).

27 ally PARP-1/PARP-2-deficient mice by using a PARP-1-deficient mouse with a Cd4-promoter-driven deleti

28 syndrome and acute myeloid leukaemia across PARP inhibitor groups was 0.73% (95% CI 0.50-1.07; I(2)=

29 repared and characterized a very long-acting PARP inhibitor.

30 35 by small nucleolar RNA (snoRNA)-activated PARP-1 inhibits AMP kinase-mediated phosphorylation of a

31 exhibits partial redundancy with an adjacent PARP-binding domain.

32 tes with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo.

33 0, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC(50) of 1.3 and 0.9 nM, respect

34 Poly(ADP-ribose)-polymerase (PARP)-1 and PARP-2 play an essential role in the DNA damage response

35 posite effects of single and dual PARP-1 and PARP-2-deficiency in modulating the antitumor response w

36 Conversely, single PARP-1 and PARP-2-deficiency tends to produce an environment with a

37 These data suggest that combining ULK1/2 and PARP inhibition may have clinical utility for the treatm

38 bility, increased necrosis, procaspase-3 and PARP processing, caspase-3 activity, and decreased AKT(S

39 apoptosis (cleaved CASP8/3 [caspase-8/3] and PARP [poly(ADP-ribose) polymerase] formation).

40 ases for the efficacy of mTORC1, CDK4/6, and PARP inhibitors in metastatic breast cancer.

41 mosome maintenance (MCM) proteins MCM2-7 and PARP and named this the mtp53-PARP-MCM axis.

42 annexin assays and caspase 3, caspase 7, and PARP-1 analyses show that these compounds activate apopt

43 lular sensitivity to crosslinking agents and PARP inhibition.

44 he treatment of several types of cancer, and PARP inhibitors have also shown therapeutic potential in

45 ires resistance to platinum chemotherapy and PARP inhibitors (PARPi).

46 lts in increased nascent DNA degradation and PARP inhibitor sensitivity.

47 stress, and increased resistance to DSBs and PARP inhibition.

48 ying a combined therapy of GLS inhibitor and PARP inhibitor to treat chemoresistant ovarian cancers,

49 evaluation of the combination of LuTate and PARP inhibition in SSTR2-expressing NET.

50 R273H enhanced the association of mtp53 and PARP on replicating DNA.

51 e function and association between mtp53 and PARP using a number of different cell lines, patient-der

52 ys a significant up-regulation of PARP1, and PARP inhibitors significantly delay tumor growth and met

53 dicate the utility of combining platinum and PARP inhibitors in this patient population.

54 to DNA-damaging agents such as platinum and PARP inhibitors.

55 sponse despite being platinum refractory and PARP inhibitor resistant.

56 , generation of reactive oxygen species, and PARP cleavage.

57 nes exhibit sensitivity to topoisomerase and PARP inhibitors, defective sister chromatid cohesion and

58 ion of Bax as well as cleaved caspase-3 and -PARP in colon cancer cells by downregulating RSK1 and MS

59 target kinase landscape of four FDA-approved PARP drugs.

60 Here, we found that olaparib, a FDA-approved PARP inhibitor, could enhance the cytotoxicity in HCC ce

61 ed for the development of PARP inhibitors as PARP-kinase polypharmacology could potentially be exploi

62 Because PARPs and the NAD(+) biosynthetic enzymes are subcellula

63 Our results highlight an interplay between PARP and mitochondrial oxidative phosphorylation in TNBC

64 d the concept of synthetic lethality between PARP inhibition and deleterious BRCA1/2 mutations, leadi

65 th potent inhibitory activities against both PARP-1/2 and PI3Kalpha/delta with pIC(50) values greater

66 Although ADP-ribosylation of histones by PARP-1 has been linked to genotoxic stress responses, it

67 onses; therefore, this enzyme is targeted by PARP inhibitors in cancer therapy.

68 olymerase 1 (PARP1)-DNA complexes trapped by PARP inhibitors, thereby promoting cell survival after d

69 free NAD(+) levels can control signaling by PARPs and redox metabolism.

70 e-3-oxo-2,3-dihydrobenzofuran-7-carboxamide; PARP-1 IC(50) = 434 nM) led to a tetrazolyl analogue (51

71 ells, promotes REV7 inactivation, and causes PARP inhibitor resistance.

72 hat induce apoptosis, including BIM, cleaved PARP, and cleaved caspase 3.

73 Clinical PARP inhibitors (PARPi) extend the lifetime of damage-in

74 tant determinant of the response to clinical PARP inhibitors.

75 Combined PARP and immune checkpoint inhibition has yielded encour

76 vide a mechanistic understanding of combined PARP and ATR inhibition in ATM-deficient models, and sup

77 andomised controlled trials (RCTs) comparing PARP inhibitor therapy versus control treatments (placeb

78 allenges in the field, such as counteracting PARP inhibitor resistance during cancer therapy and repu

79 dings warrant careful examination of current PARP inhibitors on bone metastasis and bone loss, and su

80 Differential PARP-1, AR, p53, Notch-3 and YB-1 protein levels were in

81 -1, a nuclear NAD(+) synthase, which directs PARP-1 catalytic activity to Glu and Asp residues.

82 at several structurally distinct PARPi drive PARP-1 allostery to promote release from a DNA break.

83 pinpoint opposite effects of single and dual PARP-1 and PARP-2-deficiency in modulating the antitumor

84 Analysis of tumor-infiltrating cells in dual PARP-1/PARP-2-deficiency host-mice revealed a global cha

85 Herein, we report the discovery of dual PARP/PI3K inhibitors that merge the pharmacophores of PA

86 esults indicate that 15, a first potent dual PARP/PI3K inhibitor, is a highly effective anticancer co

87 We found that dual PARP-1/PARP-2-deficiency in T cells promotes tumor growt

88 e bypassed the embryonic lethality of dually PARP-1/PARP-2-deficient mice by using a PARP-1-deficient

89 compares all toxicities associated with each PARP inhibitor, both in monotherapy and in novel combina

90 hange NAD(+) and substrate, which may enable PARP enzymes to act processively while bound to chromati

91 ur study identifies NADP(+) as an endogenous PARP inhibitor that may have implications in cancer trea

92 f the ADP-ribose (ADPR) transferase enzymes (PARP family members) that catalyze it.

93 rib (BGB-290, 139), which displays excellent PARP-1 and PARP-2 inhibition with IC(50) of 1.3 and 0.9

94 diazepinoindolone derivatives with excellent PARP enzymatic and cellular PARylation inhibition activi

95 ptake of (18)F-olaparib in tumors expressing PARP-1 (3.2% +/- 0.36% of the injected dose per gram of

96 we demonstrated that PARPi-FL, a fluorescent PARP inhibitor targeting the enzyme PARP1/2, can delinea

97 repair capacity as NAD(+) is a substrate for PARP-enzymes (mono/poly-ADP-ribosylation) and sirtuins (

98 honates as potential combination therapy for PARP inhibitors.

99 amental mechanisms and a broader utility for PARP-targeted therapeutic agents.

100 mbination may also have predictive value for PARP inhibitors.

101 Four PARP inhibitors have been approved by the FDA as cancer

102 We demonstrate that all four PARP inhibitors have a unique polypharmacological profil

103 o far led to the regulatory approval of four PARP inhibitors for the treatment of several types of ca

104 Furthermore, PARP activity, stimulated by cellular stresses, such as

105 failures can lead to human disease, and how PARP inhibitors have emerged as a novel clinical therapy

106 Importantly, PARP-1 activation has been previously linked to impaired

107 s, ultimately causing mitotic catastrophe in PARP inhibitor treated HR-proficient cells.

108 riments using mouse fibroblasts deficient in PARP-1, the ability of pol beta KDelta3A to localize to

109 ten non-placebo RCTs), with 5693 patients in PARP inhibitor groups and 3406 patients in control group

110 reveal TASOR bears a catalytically-inactive PARP domain necessary for targeted H3K9me3 deposition.

111 ctive agents targeting DNA repair, including PARP inhibitors; inhibitors of the DNA damage kinases at

112 onships with HGSC-relevant therapy including PARP inhibition and microtubule-targeting agents.

113 block DNA end resection at DSBs and increase PARP inhibitor (PARPi) sensitivity.

114 ethyltransferase inhibitors (DNMTi) increase PARP trapping and reprogram the DNA damage response to g

115 nsferrin or FeCl(3) suppressed SubAB-induced PARP cleavage.

116 lar PARylation assay, this compound inhibits PARP activity with IC(50) = 0.2 nM.

117 his effect of PARP in the tumor cell itself, PARP inhibitors have emerged as new therapeutic tools bo

118 xciting targets within synthetic lethality, (PARP, ATR, ATM, DNA-PKcs, WEE1, CDK12, RAD51, RAD52, and

119 t with bevacizumab or first-line maintenance PARP inhibitors was permitted.

120 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzym

121 anonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses.

122 ons in DDR genes beyond BRCA1/2 in mediating PARP inhibitor sensitivity is poorly understood.

123 role in DNA damage repair and small molecule PARP inhibitors have emerged as potent anticancer drugs.

124 ins MCM2-7 and PARP and named this the mtp53-PARP-MCM axis.

125 hat the antiviral activities of noncanonical PARP isozyme activities are limited by the availability

126 tion, and target engagement imaging of novel PARP-targeting agents.

127 tional group were affected by the absence of PARP-1 in a similar manner.

128 in their expression levels in the absence of PARP-1 in vivo.

129 In the absence of PARP-1, all misregulated genes coding for transcription

130 of several mobile elements in the absence of PARP-1, suggesting that PARP-1 may be involved in regula

131 Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers valid

132 4-003319-12), we investigate the activity of PARP inhibitors in 43 patients with untreated TNBC.

133 The activity of PARP-1 on H2B requires NMNAT-1, a nuclear NAD(+) synthas

134 suggesting that sequential administration of PARP and WEE1 inhibitors could maintain efficacy while a

135 cancer cell lines, and a far richer array of PARP inhibitor combination therapies for BRCA1-deficient

136 Data on the benefit of PARP inhibition as maintenance therapy in patients with

137 ed by activation of caspase-3/7, cleavage of PARP and increase in the surface expression of Annexin-V

138 in HR repair and suggest that combination of PARP inhibitors with radiotherapy could be an effective

139 mouse with a Cd4-promoter-driven deletion of PARP-2 in T cells to investigate the understudied role o

140 filing is recommended for the development of PARP inhibitors as PARP-kinase polypharmacology could po

141 ummarised with a focus on median duration of PARP inhibitor exposure, median latency period between f

142 Dysregulation of PARP activity in these processes can promote disease sta

143 Based on this effect of PARP in the tumor cell itself, PARP inhibitors have emer

144 t recent evidence for the clinical effect of PARP inhibition in breast and ovarian cancer and explore

145 strategy for enhancing the effectiveness of PARP inhibitors against TNBC.

146 alysis, and to describe clinical features of PARP inhibitor-related myelodysplastic syndrome and acut

147 , we demonstrate that different functions of PARP-1 are coordinated by interactions among these domai

148 Imaging of PARP using a radiolabeled inhibitor has been proposed fo

149 y, these results highlight the importance of PARP family members and ADPRylation in gene regulation,

150 cells highly sensitive to the inhibition of PARP activity.

151 Concomitant inhibition of PARP and PI3K pathways has been recognized as a promisin

152 Moreover, combined inhibition of PARP and Wnt/beta-catenin showed synergistic suppression

153 ells is attenuated by chemical inhibition of PARP-1.

154 Recently, inhibitors of PARP have demonstrated activity in advanced prostate tum

155 Using multiple deletional isoforms of PARP-1, lacking one or another of its three domains, as

156 eplication forks is a prominent mechanism of PARP (Poly(ADP-ribose) Polymerase) inhibitor (PARPi) res

157 sorders have been linked to misregulation of PARP-1 activity.

158 inhibitors that merge the pharmacophores of PARP and PI3K inhibitors.

159 enges to extend the therapeutic potential of PARP inhibitors to other cancer types is the absence of

160 defective cells in the prolonged presence of PARP inhibition, and concomitantly that chromatin acetyl

161 The processes of PARP activation and the PARP catalytic cycle we describe

162 ADPRylation of mRNAs, highlight the role of PARP members in RNA processing.

163 In this review we describe the role of PARP proteins and ADPRylation in all facets of this path

164 ies during the last few decades, the role of PARP-1 in transcription regulation is still not well und

165 nvestigation, particularly in the setting of PARP inhibition and HR deficiency.

166 d genes largely unexplored in the setting of PARP inhibition, many of which were associated also with

167 er of ADP-ribose chromatin scars at sites of PARP activity during DNA single-strand break repair.

168 t the most potently inhibited off-targets of PARP inhibitors identified to date and should be investi

169 This Review provides a timeline of PARP biology and medicinal chemistry, summarizes the pat

170 ral TLZ and would be useful for treatment of PARP inhibitor-sensitive cancers in which oral medicatio

171 -124 levels concomitant with upregulation of PARP-1 protein in dopaminergic-like neuronal cells in cu

172 One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA m

173 iciency and the potential therapeutic use of PARP inhibitors in DLBCL and T-ALL.

174 nces clinical management, such as the use of PARP inhibitors, which have demonstrated a progression-f

175 py, which may expand the clinical utility of PARP inhibitors.

176 an emerging concept is that the activity of PARPs and other NAD(+) consumers are regulated in a comp

177 An emerging role of PARPs in alternative splicing of mRNAs, as well as direc

178 Work on PARPs-a family of enzymes that catalyze ADP-ribosylation

179 cers of DSBs (doxorubicin or irradiation) or PARP inhibition (olaparib).

180 paired fork reversal (e.g., SMARCAL1 loss or PARP inhibition) and suggests a new strategy to modulate

181 mologous recombination DNA repair pathway or PARP inhibitor sensitivity, first in a pan-cancer cohort

182 and antitumour effects of pamiparib, an oral PARP 1/2 inhibitor, combined with tislelizumab, a humani

183 s similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a P-gp substrate a

184 ll-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, man

185 ed on the 18 placebo RCTs (n=7307 patients), PARP inhibitors significantly increased the risk of myel

186 Inhibitors of PAR polymerase (PARP) activity have been developed as cancer therapeutic

187 AR conjugation (PARylation): PAR polymerase (PARP) inhibitors can modulate the formation and dynamics

188 east in part, on poly-ADP ribose polymerase (PARP) activity.

189 are sensitive to poly(ADP)ribose polymerase (PARP) inhibitors and that the processing of spontaneous

190 ed Caspase-3 and poly ADP-ribose polymerase (PARP).

191 Poly(ADP-ribose) polymerase (PARP) and poly(ADP-ribose) glycohydrolase (PARG) are key

192 agy, and robust poly(ADP-ribose) polymerase (PARP) cleavage indicative of DNA damage and apoptosis.

193 thality between poly(ADP-ribose) polymerase (PARP) inhibition and BRCA deficiency is exploited to tre

194 ly(adenosine diphosphate-ribose) polymerase (PARP) inhibition in patients with prostate and other can

195 Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment o

196 ynthesis of the poly(ADP-ribose) polymerase (PARP) inhibitor [(18)F]olaparib.

197 ly(adenosine diphosphate ribose) polymerase (PARP) inhibitor called (125)I-KX1 to deliver Auger radia

198 ly(adenosine diphosphate-ribose) polymerase (PARP) inhibitor in a CARM1-dependent manner.

199 icity with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib against TNBC cells.

200 The poly (ADP-ribose) polymerase (PARP) inhibitor olaparib is FDA approved for the treatme

201 on to DSBs, and poly(ADP-ribose) polymerase (PARP) inhibitor resistance.

202 lnerable to the poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib, and prolonged survival in tum

203 Poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and talazoparib) are preferab

204 r resistance to poly(ADP-ribose) polymerase (PARP) inhibitors and other therapeutics and for the deve

205 re sensitive to poly(ADP-ribose) polymerase (PARP) inhibitors and platinum agents owing to deficiency

206 and maintenance poly(ADP-ribose) polymerase (PARP) inhibitors both significantly improve efficacy ver

207 Poly(ADP-ribose) polymerase (PARP) inhibitors have shown efficacy and acceptable safe

208 ersensitive to poly (ADP-ribose) polymerase (PARP) inhibitors used to treat BRCA1/2-deficient cancers

209 combination of poly (ADP-ribose) polymerase (PARP) inhibitors with drugs that inhibit the homologous

210 sensitivity to poly(ADP-ribose) polymerase (PARP) inhibitors, especially when combined with radiothe

211 ulnerability to poly(ADP-ribose) polymerase (PARP) inhibitors.

212 Poly (ADP-ribose) polymerase (PARP) plays a significant role in DNA repair responses;

213 Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a singl

214 inhibitors of poly (ADP-ribose) polymerase (PARP) that are being tested in clinical trials.

215 ilable such as poly (ADP-ribose) polymerase (PARP), epidermal growth factor receptor (EGFR), Vascular

216 repair protein poly(ADP-ribose) polymerase (PARP).

217 (BER) protein poly (ADP-ribose) polymerase (PARP).

218 Poly(ADP-ribose)-polymerase (PARP)-1 and PARP-2 play an essential role in the DNA dam

219 that depend on poly(ADP-ribose) polymerases (PARP) and the catalytic subunit of DNA-dependent protein

220 ly-adenosine diphosphate-ribose polymerases (PARPs) promote ADP-ribosylation, a highly conserved, fun

221 eby activating poly(ADP-ribose) polymerases (PARPs) to initiate DNA repair.

222 alian cells are poly-ADP-ribose-polymerases (PARPs).

223 Efforts to identify and evaluate potent PARP inhibitors have so far led to the regulatory approv

224 ly optimized to obtain analogues with potent PARP-1 IC(50) values (4-197 nM).

225 1140G [c.3418T>C], stood out with pronounced PARP inhibitor sensitivity and cytoplasmic accumulation

226 clude that TASOR is a multifunctional pseudo-PARP that directs HUSH assembly and epigenetic regulatio

227 IL3 is recruited to psoralen-ICL in a rapid, PARP-dependent manner.

228 um-based chemotherapy with a plan to receive PARP inhibitor maintenance.

229 Data are insufficient to recommend PARP inhibitor use in the early setting or in moderate-p

230 hat miR-124 post-transcriptionally regulates PARP-1.

231 stance during cancer therapy and repurposing PARP inhibitors for the treatment of non-oncological dis

232 le-agent olaparib efficacy in vitro requires PARP inhibition throughout multiple rounds of replicatio

233 Other inhibitors drive allostery to retain PARP-1 on a DNA break.

234 activation of macrophages, and various roles PARPs play in virus infections.

235 ations for the development of more selective PARP-centered therapies.

236 demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (M

237 The four drugs have largely similar PARP family inhibition profiles, but several differences

238 Conversely, single PARP-1 and PARP-2-deficiency tends to produce an environ

239 PARP-1 binds to snoRNAs, which stimulate PARP-1 catalytic activity in the nucleolus independent o

240 sitizes tumor cell to chemically synthesized PARP inhibitors.

241 re likely to benefit from ATR inhibitor than PARP inhibitor therapy.

242 ore vulnerable to ATR inhibition rather than PARP inhibitors, which is a testable hypothesis for clin

243 s based on the long-standing hypothesis that PARP inhibition will impair the repair of single strande

244 Growing evidence indicates that PARP-mediated ADPRylation events are key regulators of t

245 ts in the absence of PARP-1, suggesting that PARP-1 may be involved in regulating the expression of m

246 The PARP substrate NAD(+) is synthesized from 5-phosphoribos

247 The processes of PARP activation and the PARP catalytic cycle we describe can explain mechanisms

248 ed, open-label, phase 3 trial evaluating the PARP inhibitor olaparib in men with metastatic castratio

249 In this review, we focus on the roles of the PARP family members in inflammation and host-pathogen in

250 augments the antiproliferative effect of the PARP inhibitor olaparib.

251 le injection of a long-acting prodrug of the PARP inhibitor talazoparib in murine xenografts provides

252 g agent temozolomide in combination with the PARP inhibitor (PARPi) talazoparib.

253 tic prostate cancer patient treated with the PARP inhibitor talazoparib exhibited similar CSC marker

254 allosteric networks that operate within the PARP proteins, providing an additional level of regulati

255 ave allowed the investigation of therapeutic PARP inhibition for a variety of diseases - particularly

256 o investigate the understudied role of these PARPs in the modulation of T cell responses against AT-3

257 HRR-proficient epithelial ovarian cancers to PARP inhibitors.

258 utations in many cancers, sensitize cells to PARP inhibition by antagonizing histone demethylation an

259 more, depletion of USP52 sensitizes cells to PARP inhibition in a CtIP-dependent manner in vitro and

260 in cancer cells and thus sensitize cells to PARP inhibitor treatment.See related articles by Luo et

261 es the resistance of BRCA-deficient cells to PARP-inhibitors.

262 itizes CARM1-high, but not CARM-low, EOCs to PARP inhibitors in both orthotopic and patient-derived x

263 led (125)I-KX1 to deliver Auger radiation to PARP-1, a chromatin-binding enzyme overexpressed in neur

264 drome and acute myeloid leukaemia related to PARP inhibition versus placebo treatment in RCTs.

265 drome and acute myeloid leukaemia related to PARP inhibitor therapy were extracted on May 3, 2020, an

266 nd acute myeloid leukaemia (n=79) related to PARP inhibitor therapy were extracted.

267 drome and acute myeloid leukaemia related to PARP inhibitors, via a systematic review and safety meta

268 Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the cli

269 However, resistance to PARP inhibitors (PARPis) is common.

270 ribe can explain mechanisms of resistance to PARP inhibitors and will aid the development of better i

271 ability of stalled forks and the response to PARP inhibition in BRCA1/2-deficient cells.

272 also correlated with a patient's response to PARP inhibition therapy.

273 e important survival pathways in response to PARP-inhibitor treatment.

274 e replication of an MHV that is sensitive to PARP activity.

275 ombination repair and therefore sensitive to PARP inhibitor treatment.

276 es not significantly increase sensitivity to PARP inhibition but does sensitize to ATR inhibition.See

277 did not significantly impact sensitivity to PARP inhibition but robustly sensitized to inhibitors of

278 t expression of LMO2 predicts sensitivity to PARP inhibition, especially in combination with genotoxi

279 defect after BRCA2, but their sensitivity to PARP inhibitors has been questioned by recent clinical l

280 RDMT1 in cancer cells confers sensitivity to PARP inhibitors in vitro and in vivo.

281 ort that loss of ALC1 confers sensitivity to PARP inhibitors, methyl-methanesulfonate, and uracil mis

282 biomarkers for breast cancer sensitivity to PARP inhibitors.

283 reat cancer relates to their ability to trap PARP-1 at the site of a DNA break.

284 enzyme, they have variable abilities to trap PARP-1.

285 alkylation-induced DNA breaks as wild type, PARP-1 activation is undetectable in AAG-deficient cells

286 are pertinent to clinical applications where PARP-1 trapping is either desirable or undesirable.

287 understand the molecular mechanism by which PARP enzymes recognize DNA breaks within chromatin, we d

288 It may also explain the mechanism by which PARP inhibitor regulates early DNA damage repair.

289 es the pathophysiological processes in which PARP plays a role and highlights key opportunities and c

290 ent understanding of the mechanisms by which PARPs promote or suppress proinflammatory activation of

291 While PARP inhibitors have been tested in clinical trials and

292 so show that the combination of KP372-1 with PARP inhibition creates enhanced cytotoxicity in pancrea

293 chronic treatment of BRCA1-mutant cells with PARP inhibitors, resistant clones can arise via several

294 xhibit "BRCAness," which in combination with PARP inhibition can similarly induce synthetic lethality

295 onstrated that uL3 physically interacts with PARP-1 affecting E2F1 transcriptional activity.

296 PSN-1 xenografts), correlating linearly with PARP-1 expression.

297 Following cessation of monotherapy with PARP or WEE1 inhibitors, effects of these inhibitors per

298 f pamiparib shows similar binding sites with PARP with other PARP inhibitors, but pamiparib is not a

299 BRCA2-deficient PCs, and combining SPA with PARP or DNA-PKcs inhibition further repressed growth.

300 nature analysis, that may be targetable with PARP inhibitors.