ライフサイエンスコーパス: PARPi

1 PARPi also show promising activity in more common cancer

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

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

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

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

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

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

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

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

10 between nucleases that initiate HR can drive PARPi resistance.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

36 sensitizes MLL leukemia to PARP inhibitors (PARPis).

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

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

39 uentially bypassed during the acquisition of PARPi resistance.

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

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

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

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

44 resistance mechanisms that limit efficacy of PARPi monotherapy.

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

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

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

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

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

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

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

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

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

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

55 from patients to investigate how to overcome PARPi resistance.

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

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

58 11q protein was capable of promoting partial PARPi and cisplatin resistance relative to full-length B

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

75 nsitized cells carrying exon 11 mutations to PARPi treatment.

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

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

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

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

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

81 combination (HR) defects become sensitive to PARPi.

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

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

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

85 equently, increasing cellular sensitivity to PARPi.

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

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

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

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

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

91 ificantly reduced tumor growth compared with PARPi therapy alone.

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

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

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