ライフサイエンスコーパス: PARPi

1 PARPi also potentiated IFN-gamma-induced PD-L1 expressio

2 PARPi also show promising activity in more common cancer

3 PARPi exert their therapeutic effects mainly through the

4 PARPi possess both PARP1 inhibition and PARP1 trapping a

5 PARPi promoted accumulation of cytosolic DNA fragments b

6 PARPi- and cisplatin-resistant clones did not harbor sec

7 PARPi-FL also allowed identification of compromised marg

8 PARPi-FL was further able to differentiate tumor from lo

9 PARPis are not recommended for use in combination with c

10 Inhibitors of poly-ADP-ribose polymerase 1 (PARPi) are highly effective in killing cells deficient i

11 In addition, it synergizes with olaparib (a PARPi) to trigger synthetic lethality.

12 tinum-based therapy, who have not received a PARPi and have a g/sBRCA1/2, or whose tumor demonstrates

13 or patients with EOC who have not received a PARPi and have responded to platinum-based therapy regar

14 Treatment with a PARPi should be offered to patients with recurrent EOC t

15 in clinically relevant platinum and acquired PARPi-resistant patient-derived xenografts (PDXs) models

16 e PARPi driven therapies and hamper acquired PARPi resistance.

17 requently not observed in models of acquired PARPi-resistance, suggesting the existence of alternativ

18 volutionary analyses suggested that acquired PARPi resistance arose via clonal selection from an intr

19 The first clinical trial with a single agent PARPi failed to show significant responses, but preclini

20 rapy (second line or more) with single-agent PARPi may be offered for patients with EOC who have not

21 Although PARPi induced a general DNA damage response in SCLC cell

22 Although PARPi-induced innate immunity is highly desirable in hum

23 ATRi and PARPi appeared to induce the strongest increase in poten

24 and sensitized cancer cells to cisplatin and PARPi.

25 uitment, RAD51 nucleofilament formation, and PARPi resistance.

26 a) in BRCA1-deficient cells restores HDR and PARPi resistance.

27 promoting homologous recombination (HR) and PARPi resistance.

28 a discordance in sensitivity to platinum and PARPi, with potential implications for previously report

29 r cross-resistance mechanism to platinum and PARPi.

30 as critical regulators of fork stability and PARPi responses in BRCA-deficient cells, which provides

31 n analog to rucaparib, a clinically approved PARPi, and is a candidate biomarker for PARPi response.

32 The guideline pertains to patients who are PARPi naive.

33 igh-grade serous ovarian cancer cells become PARPi sensitive, undergo mitotic catastrophe, and die.

34 Despite the lack of BRCA1, PARPi-resistant cells regain RAD51 loading to DNA double

35 istant T127 tumors and markedly decreased by PARPi in T22 tumors.

36 ccumulation of Rad51 in chromatin induced by PARPi, resulting in DNA damage being channelled through

37 s in DNA repair whose growth is inhibited by PARPi.

38 In contrast, inhibition of PARP by PARPi attenuates alkylating DNA damage-induced EZH2 down

39 Compared with BRCA1-proficient cells, PARPi-resistant BRCA1-deficient cells are increasingly d

40 amage sites even in the presence of clinical PARPi, suggesting the persistent foci are not caused by

41 We demonstrated that clinical PARPi, including olaparib and rucaparib, have cell-auton

42 east cancers that may respond to combination PARPi treatments.

43 DNA repair processes allow our combinatorial PARPi and DNMTi therapy to robustly sensitize NSCLC cell

44 rapy success of both drug classes, combining PARPi with ICB may be a safe and well-tolerated strategy

45 umors and provides a rationale for combining PARPi with immunotherapy in patients with cancer.

46 hibition in GSCs suppressed HR and conferred PARPi sensitivity, with ATR inhibitors synergizing with

47 s common in BRCA1-deficient cancers, confers PARPi resistance and correlates with poor prognosis.

48 Conversely, HOXA9 overexpression confers PARPi resistance to AML1-ETO and PML-RARalpha transforme

49 ring C5aR1(hi) cells increases and decreases PARPi sensitivity, respectively.

50 nces of 53BP1 deficiency, such as diminished PARPi efficacy in BRCA1-deficient cells and altered repa

51 lls, with common repair defects but distinct PARPi responses, reveal gaps as a distinguishing factor.

52 We found that several structurally distinct PARPi drive PARP-1 allostery to promote release from a D

53 Sensitivity to PARPi-ATRi in diverse PARPi and platinum-resistant models, including BRCA1/2 r

54 By trapping PARP on DNA, PARPi prevents the completion of gap repair until the ne

55 between nucleases that initiate HR can drive PARPi resistance.

56 ines the efficacy of PARP1 inhibitory drugs (PARPi) in BRCA1-deficient cancers.

57 cal imaging of OSCC with the fluorescent dye PARPi-FL.

58 nd have shown promising therapeutic effects, PARPi used as single agents are clinically limited to pa

59 ludes with a description of ongoing/emerging PARPi clinical trials in patients with Ewing sarcoma.

60 rase inhibitors (DNMTis) plus PARPis enhance PARPi efficacy in BRCA-proficient AML subtypes, breast,

61 n urgent need for novel targets that enhance PARPi efficacy.

62 roduce a mechanism-based strategy to enhance PARPi efficacy based on DNA damage-related binding betwe

63 e HuR-PARG axis as an opportunity to enhance PARPi-based therapies.

64 ow elucidate how epigenetic therapy enhances PARPi efficacy in the setting of BRCA-proficient cancer.

65 CA-mutated epithelial ovarian cancers (EOC), PARPi resistance remains a major challenge.

66 oved PARPi, and is a candidate biomarker for PARPi response.

67 WE1 expression as a predictive biomarker for PARPi.

68 e have identified an alternative pathway for PARPi-mediated growth control in BRCA1/2-intact breast c

69 Thus, there are two rationales for PARPi in the treatment of Ewing sarcoma: to disrupt the

70 mised DNA-binding activities is required for PARPi-induced innate immune response.

71 (PARP) inhibitors (PARPis), but the role for PARPis in BRCA-proficient cancers is not well establishe

72 ts with breast cancer likely to benefit from PARPi beyond gBRCA1/2 mutation carriers.

73 hese patients could potentially benefit from PARPis.

74 reveal a novel molecular mechanism governing PARPi sensitivity in AML.

75 However, PARPi-resistant cells are remarkably more sensitive to A

76 for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatial

77 blish POLE4 as a promising target to improve PARPi driven therapies and hamper acquired PARPi resista

78 BRCA1 exon 11 skipping was elevated in PARPi resistant PDX tumors.

79 i-inflammatory activity, that is enriched in PARPi resistant T127 tumors and markedly decreased by PA

80 t RAD51 loading to DSBs and stalled forks in PARPi-resistant BRCA1-deficient cells, overcoming both r

81 inds and posttranslationally modifies HuR in PARPi-treated PDAC cells.

82 mRNA, yet the role of m(6)A modification in PARPi resistance has not previously been explored.

83 this review, we summarize recent progress in PARPi therapy in brain tumors, and discuss current oppor

84 umors, stabilize stalled forks, resulting in PARPi resistance in BRCA-deficient cells.

85 ect to proteasomal degradation, resulting in PARPi sensitivity.

86 he 53BP1-dependent repair pathway results in PARPi resistance in BRCA1 patients.

87 lus PARPis, versus each drug alone, increase PARPi efficacy, increasing amplitude and retention of PA

88 PARP inhibition (PARPi) kills tumor cells defective in homologous recombi

89 benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance li

90 esection, RAD51 loading, and PARP inhibitor (PARPi) resistance.

91 n-label phase 2 study of the PARP inhibitor (PARPi) rucaparib in relapsed high-grade ovarian carcinom

92 Platinum and PARP inhibitor (PARPi) sensitivity commonly coexist in epithelial ovaria

93 section at DSBs and increase PARP inhibitor (PARPi) sensitivity.

94 mide in combination with the PARP inhibitor (PARPi) talazoparib.

95 PARP inhibitor (PARPi) therapy targets BRCA1/2 mutant tumor cells, but a

96 carcinomas are sensitive to PARP inhibitor (PARPi) therapy; however, resistance arises.

97 in vitro sensitivity to the PARP inhibitor (PARPi), rucaparib.

98 ly (ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib has been approved for treatment of advan

99 ly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal

100 s of poly (ADP-ribose) polymerase inhibitor (PARPi) resistance in BRCA2; p53-deficient mouse mammary

101 m and poly(ADP-ribose) polymerase inhibitor (PARPi) therapy; however, resistance invariably arises in

102 hosphate [ADP]-ribose) polymerase inhibitor (PARPi) treatment] were exploratory.

103 ARP (Poly(ADP-ribose) Polymerase) inhibitor (PARPi) resistance in BRCA-deficient tumors.

104 DP-ribose) polymerase-1 (PARP-1) inhibitors (PARPi) to treat cancer relates to their ability to trap

105 unction, the development of PARP inhibitors (PARPi) and the evidence for targeting PARP in Ewing sarc

106 As most currently approved PARP inhibitors (PARPi) are MDR1 substrates, prior chemotherapy may preco

107 PARP inhibitors (PARPi) benefit only a fraction of breast cancer patients

108 Clinical PARP inhibitors (PARPi) extend the lifetime of damage-induced PARP1/2 foc

109 PARP inhibitors (PARPi) have shown remarkable therapeutic efficacy agains

110 Clinically approved PARP inhibitors (PARPi) have shown significant efficacy as monotherapy in

111 h initial response rates to PARP inhibitors (PARPi) in BRCA-mutated epithelial ovarian cancers (EOC),

112 One example is the use of PARP inhibitors (PARPi) in oncology patients with BRCA mutations.

113 Acquired resistance to PARP inhibitors (PARPi) is a major challenge for the clinical management

114 the combination of TMZ with PARP inhibitors (PARPi) potently elicited double-strand DNA breaks, repli

115 PARP inhibitors (PARPi) prevent cancer cell growth by inducing synthetic

116 PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) poly

117 ensitivity of PDAC cells to PARP inhibitors (PARPi).

118 ich makes them sensitive to PARP inhibitors (PARPi).

119 d to development of several PARP inhibitors (PARPi).

120 o platinum chemotherapy and PARP inhibitors (PARPi).

121 y (ADP-ribose) polymerase (PARP) inhibitors (PARPi) has long been attributed to this defect.

122 y (ADP-ribose) polymerase (PARP) inhibitors (PARPi) have been approved in multiple diseases, includin

123 ly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) is toxic to cells with defects in homologous reco

124 unomodulatory functions of PARP1 inhibitors (PARPi) underlie their clinical activities in various BRC

125 Poly(ADP ribose) polymerase inhibitors (PARPi) have efficacy in triple negative breast (TNBC) an

126 ugh poly (ADP-ribose) polymerase inhibitors (PARPi) have shown promising therapeutic effects in TNBC

127 y to poly(ADP-ribose) polymerase inhibitors (PARPi) in BRCA1-deficient cancers.

128 ith poly (ADP-ribose) polymerase inhibitors (PARPi) is impeded by inevitable resistance and associate

129 Poly-(ADP-ribose) polymerase inhibitors (PARPi) selectively kill breast and ovarian cancers with

130 Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA repair d

131 y to poly(ADP-ribose) polymerase inhibitors (PARPi).

132 PARP inhibitors (PARPis) are being used in patients with BRCA1/2 mutation

133 PARP inhibitors (PARPis) are used clinically to treat BRCA-mutated breast

134 PARP inhibitors (PARPis) have clinical efficacy in BRCA-deficient cancers

135 Clinical activity of PARP inhibitors (PARPis) in BRCA1/2 mutant cancers validated the concept

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

137 Among them, PARP inhibitors (PARPis) were shown to induce unprecedented improvement i

138 ce the clinical response to PARP inhibitors (PARPis), understanding the mechanisms underlying PARPi s

139 sensitizes MLL leukemia to PARP inhibitors (PARPis).

140 ically relevant response to PARP inhibitors (PARPis).

141 r, making them sensitive to PARP inhibitors (PARPis).

142 ly(ADP ribose) polymerase (PARP) inhibitors (PARPis) exhibit antitumor immunity that occurs in a stim

143 y-(ADP-ribose) polymerase (PARP) inhibitors (PARPis) selectively kill BRCA1/2-deficient cells, but th

144 y (ADP-ribose) polymerase (PARP) inhibitors (PARPis), but the role for PARPis in BRCA-proficient canc

145 Poly (ADP-ribose) polymerase inhibitors (PARPis) are clinically effective predominantly for BRCA-

146 ough poly(ADP-ribose) polymerase inhibitors (PARPis) benefit a subset of patients with mCRPC and BRCA

147 and poly-(ADP)-ribose polymerase inhibitors (PARPis).

148 to poly (ADP-ribose) polymerase inhibitors (PARPis).

149 Mechanistically, PARPi generated cytoplasmic chromatin fragments with cha

150 We found that resistance to multiple PARPi emerged with reduced expression of TET2 (ten-eleve

151 Further, we generated a new PARPi compound, converting an allosteric pro-release com

152 uentially bypassed during the acquisition of PARPi resistance.

153 We show that acquisition of PARPi-resistance is accompanied by increased ATR-CHK1 ac

154 Results: After topical application of PARPi-FL on freshly excised cone biopsy samples, the nuc

155 c proteins, and may represent a biomarker of PARPi resistance.

156 foci have been widely used as biomarkers of PARPi response.

157 but preclinical evidence for combinations of PARPi with chemotherapy or radiotherapy is very promisin

158 as focused on the downstream consequences of PARPi exposure to tackle resistance, the immediate effec

159 Because genomic hmdU is a key determinant of PARPi sensitivity, targeting DNPH1 provides a promising

160 screens which reveal genetic determinants of PARPi response in wildtype or BRCA2-knockout cells.

161 Nevertheless, the preclinical discovery of PARPi synthetic lethality and the route to clinical appr

162 Here we examine the effect of PARPi on HR-proficient cells.

163 enotype resulted from an on-target effect of PARPi on PARP1.

164 These effects of PARPi were further enhanced by immune checkpoint blockad

165 vide a mechanistic rationale for efficacy of PARPi in cancer cells lacking defects in DNA repair whos

166 he mechanism behind the clinical efficacy of PARPi in patients with both BRCA-wild-type and BRCA-muta

167 Here we show how the efficacy of PARPi in triple-negative breast cancers (TNBC) can be ex

168 resistance mechanisms that limit efficacy of PARPi monotherapy.

169 Although different forms of PARPi all target the catalytic center of the enzyme, the

170 ributor of the immunomodulatory functions of PARPi.

171 Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of hu

172 Intravenous injection of PARPi-FL has significant potential for clinical translat

173 C-derived orthotopic tumors, irrespective of PARPi-sensitivity.

174 gs elucidate a novel regulatory mechanism of PARPi resistance in EOC by showing that m(6)A modificati

175 These data inform on mechanism of PARPi resistance in HR-deficient cells and present Dicty

176 ly validated exon skipping as a mechanism of PARPi resistance.

177 n forks, enabling two distinct mechanisms of PARPi resistance.

178 dentified PARP1 as the principal mediator of PARPi-induced T cell death.

179 screen, we identified EMI1 as a modulator of PARPi sensitivity in triple-negative breast cancer (TNBC

180 i response, and identifies novel pathways of PARPi resistance in BRCA2-deficient cells.

181 pite initial excitement for the potential of PARPi as single agent therapy in Ewing sarcoma, the emer

182 d are able to proliferate in the presence of PARPi.

183 ta-catenin showed synergistic suppression of PARPi-resistant cells in vitro and in vivo in a xenograf

184 ble data across all the randomized trials of PARPi in first-line mCRPC was selected.

185 ive biomarkers that advance understanding of PARPi response, and identifies novel pathways of PARPi r

186 ially relevant for a potential future use of PARPi as prophylactic agents in BRCA1 mutation carriers.

187 This strategy aims to widen the use of PARPi in BRCA-competent and olaparib-resistant cancers,

188 In addition, determining the optimal use of PARPi within drug combination approaches has been challe

189 Methods: Here, we describe the use of PARPi-FL, a fluorescent inhibitor of poly[adenosine diph

190 is also clinical evidence for the utility of PARPi in breast and ovarian cancers without BRCA mutatio

191 hese studies describe a potential utility of PARPi-induced synthetic lethality for leukemia treatment

192 ng to broaden the therapeutic application of PARPis identified sensitivity biomarkers and rationale c

193 ion forks is key for the lethality effect of PARPis, we investigated the combined effects of SLFN11 e

194 introduces a strategy to enhance efficacy of PARPis in treating cancer.

195 rtunities for, and challenges to, the use of PARPis in neuro-oncology.

196 serous or endometrioid EOC should be offered PARPi maintenance therapy with niraparib.

197 of SLFN11 expression and BRCA deficiency on PARPi sensitivity and ssDNA gap formation in human cance

198 ications for previously reported and ongoing PARPi trials in this disease.

199 of the MSLN-TTC in combination with ATRi or PARPi was investigated in the OVCAR-3 and OVCAR-8 xenogr

200 ibiting PARylation by either hyperthermia or PARPi induced lethal DSB upon chemotherapy treatment not

201 espond to PARPi alone, and potentially other PARPi-refractory tumors.

202 represents a potential strategy to overcome PARPi resistance.

203 from patients to investigate how to overcome PARPi resistance.

204 Although inhibitors of PARP (PARPi) have emerged as small molecule drugs and have sho

205 ciently as pharmacologic inhibitors of PARP (PARPi), producing comparable delay in DNA repair, induct

206 sensitive to ATRi when combined with PARPi (PARPi-ATRi).

207 overexpression of Rdd-BRCA1 promoted partial PARPi and cisplatin resistance.

208 11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length B

209 In a mouse xenograft model of human PDAC, PARPi monotherapy combined with targeted silencing of Hu

210 Low doses of DNMTis plus PARPis, versus each drug alone, increase PARPi efficacy,

211 A methyltransferase inhibitors (DNMTis) plus PARPis enhance PARPi efficacy in BRCA-proficient AML sub

212 BRCA reversion mutation in previously PARPi-treated BRCA-mutant patients was not associated wi

213 Prior PARPi, platinum-refractory disease, or progression on mo

214 t homology-dependent DNA repair, and promote PARPi resistance.

215 arbor secondary reversion mutations; rather, PARPi and platinum resistance required increased express

216 ase FZD10 mRNA m(6)A modification and reduce PARPi sensitivity, which correlated with an increase in

217 onstitution of EMI1 expression reestablishes PARPi sensitivity both in cellular systems and in an ort

218 activity; however, depleting MSH2 reinstates PARPi sensitivity and gaps.

219 Loss of Artemis restores PARPi resistance in BRCA1-deficient cells.

220 Similar to 53BP1, loss of TIRR restores PARPi resistance in BRCA1-deficient cells.

221 ons, leading to clinical approval of several PARPis.

222 reclinical data now strongly support testing PARPi in combination with chemo/radiotherapy clinically.

223 oral cavity carcinoma, we demonstrated that PARPi-FL, a fluorescent PARP inhibitor targeting the enz

224 These findings indicate that PARPi-ATRi is a highly promising strategy for OVCAs that

225 Here we show that PARPi-mediated modulation of the immune response contrib

226 ibition is a unique strategy to overcome the PARPi resistance of BRCA-deficient cancers.

227 hits from our screens, robustly reverses the PARPi sensitivity caused by BRCA2-deficiency.

228 pression, we found that combination with the PARPi niraparib increased DNA damage and downregulated h

229 ient in homologous recombination (HR); thus, PARPi have been clinically utilized to successfully trea

230 ersensitization of BRCA-deficient cancers to PARPi therapy.

231 HRD, sensitizing BRCA-proficient cancers to PARPi.

232 estore sensitivity of dnapkcs-exo1- cells to PARPi, indicating redundancy between nucleases that init

233 supresses the sensitivity of exo1- cells to PARPi, indicating this pathway drives synthetic lethalit

234 t/beta-catenin sensitizes resistant cells to PARPi.

235 rive resistance of the HR-deficient cells to PARPi.

236 r sensitizes the BRCA-mutant breast cells to PARPi.

237 splice isoforms 11 and 11q can contribute to PARPi resistance by splicing out the mutation-containing

238 )A modification of FZD10 mRNA contributes to PARPi resistance by upregulating the Wnt/beta-catenin pa

239 , our results show that m(6)A contributes to PARPi resistance in BRCA-deficient EOC cells by upregula

240 )A modification of FZD10 mRNA contributes to PARPi resistance in BRCA-deficient EOC cells via upregul

241 ates with oncogenic function, contributes to PARPi sensitivity in breast cancer cells.

242 e hypomorphic and capable of contributing to PARPi and platinum resistance when expressed at high lev

243 hromatin environment and its contribution to PARPi toxicity remains elusive.

244 nation (HR) deficient, are hypersensitive to PARPi through the mechanism of synthetic lethality.

245 ding premature aging and hypersensitivity to PARPi.

246 we investigated the mechanisms that lead to PARPi and platinum resistance in the SUM1315MO2 breast c

247 RFs and a potential resistance mechanism to PARPi and cisplatin.

248 nsitized cells carrying exon 11 mutations to PARPi treatment.

249 trategy for OVCAs that acquire resistance to PARPi and platinum.

250 with other targeted therapies, resistance to PARPi arises in advanced disease.

251 1-deficient TNBC cells develop resistance to PARPi by downregulating EMI1 and restoring RAD51-depende

252 identify a novel mechanism of resistance to PARPi through regulation of RAD51 protein stability via

253 -deficient cells that acquired resistance to PARPi were resensitized by treatment with hmdU and DNPH1

254 chemotherapy may precondition resistance to PARPi.

255 even for low-Myc GSCs that do not respond to PARPi alone, and potentially other PARPi-refractory tumo

256 enzyme USP15 affects cancer cell response to PARPi by regulating HR.

257 However, positive response to PARPi is not universal, even among patients with HR-defi

258 are any differences in cellular response to PARPi olaparib depending on the BRCA1 mutation type.

259 CA1/2 is the best determinant of response to PARPi, a significant percentage of the patients do not s

260 In response to PARPi, CDK18 facilitates ATR activation by interacting w

261 P1 retention at these lesions in response to PARPi.

262 omplete and durable therapeutic responses to PARPi-ATRi that significantly increase survival are obse

263 SUM1315MO2 cells were initially sensitive to PARPi and cisplatin but readily acquired resistance.

264 ns in either BRCA1 or BRCA2 are sensitive to PARPi because they have a specific type of DNA repair de

265 combination (HR) defects become sensitive to PARPi.

266 , a critical factor for HR, are sensitive to PARPi.

267 y in a HGSOC-PDX with reduced sensitivity to PARPi by overcoming replication fork protection.

268 CA)-mutant cells and enhanced sensitivity to PARPi by up to 250-fold, while overcoming several resist

269 tion affected HR or conferred sensitivity to PARPi or other double-strand break-inducing agents.

270 m-like cells (GSCs) generates sensitivity to PARPi via Myc-mediated transcriptional repression of CDK

271 tion can leverage cancer cell sensitivity to PARPi, facilitating the clinical use of c-myc as a predi

272 Sensitivity to PARPi-ATRi in diverse PARPi and platinum-resistant model

273 equently, increasing cellular sensitivity to PARPi.

274 level, and increased cellular sensitivity to PARPi.

275 5461 has a different sensitivity spectrum to PARPi involving MRE11-dependent degradation of replicati

276 BP1(-/-) cells or tumors become resistant to PARPis.

277 understanding of the favorable responses to PARPis in SLFN11-expressing and BRCA-deficient tumors.

278 contribution of these two mechanisms toward PARPi-induced innate immune signaling, however, is poorl

279 is), understanding the mechanisms underlying PARPi sensitivity is urgently needed.

280 o fork breakage and trapping of PARP1/2 upon PARPi treatment, resulting in hypersensitivity.

281 ta provide a preclinical rationale for using PARPi as immunomodulatory agents in appropriately molecu

282 ts provide a mechanistic rationale for using PARPi as immunomodulatory agents to harness the therapeu

283 n of cGAS-STING signaling induced by various PARPi closely depends on their PARP1 trapping activities

284 ctional RAD51 assay correlates with in vitro PARPi sensitivity, clinical platinum sensitivity, and im

285 HRD was associated with higher ex vivo PARPi sensitivity and clinical platinum sensitivity.

286 By tackling the challenges associated with PARPi resistance and exploring novel combination therapi

287 Combining MYC blockade with PARPi yielded synthetic lethality in MYC-driven TNBC cel

288 1 is a promising therapy in combination with PARPi in HR-deficient HGSOC and also as a single agent f

289 DNMTi in combination with PARPi up-regulate broad innate immune and inflammasome-l

290 ly more sensitive to ATRi when combined with PARPi (PARPi-ATRi).

291 ATR inhibitor VE822 combined with PARPi extended survival of mice bearing GSC-derived orth

292 ificantly reduced tumor growth compared with PARPi therapy alone.

293 and cancer stem cell property compared with PARPi-untreated cells.

294 our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve

295 xaliplatin and 5-fluorouracil), but not with PARPi therapy.

296 CX-5461 co-operates with PARPi in exacerbating replication stress and enhances th

297 PDAC cells treated with PARPi stimulated translocation of HuR from the nucleus t

298 Treatment with PARPi or mutation of the ADP-ribosylation sites reduces

299 chanisms that cause synthetic lethality with PARPis.

300 tivity, with ATR inhibitors synergizing with PARPis or sensitizing GSCs.