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YANG Wanwan, YE Fangyu, WU Yujia, WANG Haochen, ZHAO Li. Research progress of PARP inhibitors in cancers and their drug resistance[J]. Journal of China Pharmaceutical University, 2022, 53(5): 525-534. DOI: 10.11665/j.issn.1000-5048.20220503
Citation: YANG Wanwan, YE Fangyu, WU Yujia, WANG Haochen, ZHAO Li. Research progress of PARP inhibitors in cancers and their drug resistance[J]. Journal of China Pharmaceutical University, 2022, 53(5): 525-534. DOI: 10.11665/j.issn.1000-5048.20220503

Research progress of PARP inhibitors in cancers and their drug resistance

Funds: This study was supported by the National Natural Science Foundation of China (No.82273962)
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  • Received Date: March 03, 2022
  • Revised Date: April 10, 2022
  • Poly ADP-ribose polymerase-1 (PARP-1) plays a vital role in organisms, including regulating repair of DNA, maintaining genome stability, regulating cell proliferation, differentiation, and death.At present, PARP inhibitors have been made some breakthrough in the treatment of breast cancer, ovarian cancer, prostate cancer and pancreatic cancer.However, PARP inhibitors have certain limitations in other malignant tumors and patients who are resistant to PARP-1 inhibitors.This article summarizes the research on PARP inhibitors in lung cancer, hepatocellular carcinoma, glioblastoma, leukemia and cervical cancer, and introduces the strategies of combining other anti-tumor drugs such as DNA repair inhibitors, immune checkpoint inhibitors, anti-angiogenic drugs and other chemotherapeutic drugs to solve their drug resistance, which provides some reference for the wide clinical application of PARP inhibitors in the future.
  • [1]
    . Mol Cancer,2020,19(1):49.
    [2]
    Wen H.Chinese expert consensus on management of adverse events of PARP inhibitor (2021 ed)[J]. Chin J Pract Gynecol Obstet(中国实用妇科与产科杂志),2021,37(11):1119-1130.
    [3]
    Hodgson DR,Dougherty BA,Lai ZW,et al. Candidate biomarkers of PARP inhibitor sensitivity in ovarian cancer beyond the BRCA genes[J]. Br J Cancer,2018,119(11):1401-1409.
    [4]
    Golan T,Kindler HL,Park JO,et al. Geographic and ethnic heterogeneity of germLine BRCA1 or BRCA2 mutation prevalence among patients with metastatic pancreatic cancer screened for entry into the POLO trial[J]. J Clin Oncol,2020,38(13):1442-1454.
    [5]
    González-Martín A,Pothuri B,Vergote I,et al. Niraparib in patients with newly diagnosed advanced ovarian cancer[J]. N Engl J Med,2019,381(25):2391-2402.
    [6]
    Mateo J,Porta N,Bianchini D,et al. Olaparib in patients with metastatic castration-resistant prostate cancer with DNA repair gene aberrations (TOPARP-B):a multicentre,open-label,randomised,phase 2 trial[J]. Lancet Oncol,2020,21(1):162-174.
    [7]
    Byers LA,Wang J,Nilsson MB,et al. Proteomic profiling identifies dysregulated pathways in small cell lung cancer and novel therapeutic targets including PARP1[J]. Cancer Discov,2012,2(9):798-811.
    [8]
    de Bono J,Ramanathan RK,Mina,et al. Phase I,dose-escalation,two-part trial of the PARP inhibitor talazoparib in patients with advanced germLine BRCA1/2 mutations and selected sporadic cancers[J]. Cancer Discov,2017,7(6):620-629.
    [9]
    Atrafi F,Groen HJM,Byers LA,et al. A phase I dose-escalation study of veliparib combined with carboplatin and etoposide in patients with extensive-stage small cell lung cancer and other solid tumors[J]. Clin Cancer Res,2019,25(2):496-505.
    [10]
    Owonikoko TK,Dahlberg SE,Khan SA,et al. A phase 1 safety study of veliparib combined with cisplatin and etoposide in extensive stage small cell lung cancer:a trial of the ECOG-ACRIN Cancer Research Group (E2511)[J]. Lung Cancer,2015,89(1):66-70.
    [11]
    Pietanza MC,Waqar SN,Krug LM,et al. Randomized,double-blind,phase II study of temozolomide in combination with either veliparib or placebo in patients with relapsed-sensitive or refractory small-cell lung cancer[J]. J Clin Oncol,2018,36(23):2386-2394.
    [12]
    Willis SE,Winkler C,Roudier MP,et al. Retrospective analysis of Schlafen11 (SLFN11) to predict the outcomes to therapies affecting the DNA damage response[J]. Br J Cancer,2021,125(12):1666-1676.
    [13]
    Farago AF,Yeap BY,Stanzione M,et al. Combination olaparib and temozolomide in relapsed small-cell lung cancer[J]. Cancer Discov,2019,9(10):1372-1387.
    [14]
    Laird JH,Lok BH,Ma J,et al. Talazoparib is a potent radiosensitizer in small cell lung cancer cell lines and xenografts[J]. Clin Cancer Res,2018,24(20):5143-5152.
    [15]
    Marcar L,Bardhan K,Gheorghiu L,et al. Acquired resistance of EGFR-mutated lung cancer to tyrosine kinase inhibitor treatment promotes PARP inhibitor sensitivity[J]. Cell Rep,2019,27(12):3422-3432.e4.
    [16]
    Zhang ZM,Lian XJ,Xie W,et al. Role of PARP1-mediated autophagy in EGFR-TKI resistance in non-small cell lung cancer[J]. Sci Rep,2020,10(1):20924.
    [17]
    Yang XD,Kong FE,Qi L,et al. PARP inhibitor olaparib overcomes sorafenib resistance through reshaping the pluripotent transcriptome in hepatocellular carcinoma[J]. Mol Cancer,2021,20(1):20.
    [18]
    Wang C,Tang HY,Geng AK,et al. Rational combination therapy for hepatocellular carcinoma with PARP1 and DNA-PK inhibitors[J]. Proc Natl Acad Sci U S A,2020,117(42):26356-26365.
    [19]
    Lin L,Zhang YD,Chen ZY,et al. The clinicopathological significance of miR-149 and PARP-2 in hepatocellular carcinoma and their roles in chemo/radiotherapy[J]. Tumour Biol,2016,37(9):12339-12346.
    [20]
    Wang S,Yang FJ,Wang X,et al. PARP-1 promotes tumor recurrence after warm ischemic liver graft transplantation via neutrophil recruitment and polarization[J]. Oncotarget,2017,8(51):88918-88933.
    [21]
    Jannetti SA,Carlucci G,Carney B,et al. PARP-1-targeted radiotherapy in mouse models of glioblastoma[J]. J Nucl Med,2018,59(8):1225-1233.
    [22]
    Wu SF,Gao F,Zheng SY,et al. EGFR amplification induces increased DNA damage response and renders selective sensitivity to talazoparib (PARP inhibitor) in glioblastoma[J]. Clin Cancer Res,2020,26(6):1395-1407.
    [23]
    Boukerroucha M,Josse C,Segers K,et al. BRCA1 germLine mutation and glioblastoma development:report of cases[J]. BMC Cancer,2015,15:181.
    [24]
    Xavier MA,Rezende F,Titze-de-Almeida R,et al. BRCAness as a biomarker of susceptibility to PARP inhibitors in glioblastoma multiforme[J]. Biomolecules,2021,11(8):1188.
    [25]
    Ghorai A,Mahaddalkar T,Thorat R,et al. Sustained inhibition of PARP-1 activity delays glioblastoma recurrence by enhancing radiation-induced senescence[J]. Cancer Lett,2020,490:44-53.
    [26]
    Hanna C,Kurian KM,Williams K,et al. Pharmacokinetics,safety,and tolerability of olaparib and temozolomide for recurrent glioblastoma:results of the phase I OPARATIC trial[J]. Neuro Oncol,2020,22(12):1840-1850.
    [27]
    Wu SF,Li XL,Gao F,et al. PARP-mediated PARylation of MGMT is critical to promote repair of temozolomide-induced O6-methylguanine DNA damage in glioblastoma[J]. Neuro Oncol,2021,23(6):920-931.
    [28]
    Padella A,Ghelli Luserna Di Rorà A,Marconi G,et al. Targeting PARP proteins in acute leukemia:DNA damage response inhibition and therapeutic strategies[J]. J Hematol Oncol,2022,15(1):10.
    [29]
    Li X,Li CY,Jin JR,et al. High PARP-1 expression predicts poor survival in acute myeloid leukemia and PARP-1 inhibitor and SAHA-bendamustine hybrid inhibitor combination treatment synergistically enhances anti-tumor effects[J]. EBioMedicine,2018,38:47-56.
    [30]
    Gojo I,Beumer JH,Pratz KW,et al. A phase 1 study of the PARP inhibitor veliparib in combination with temozolomide in acute myeloid leukemia[J]. Clin Cancer Res,2017,23(3):697-706.
    [31]
    Raspaglio G,Buttarelli M,Filippetti F,et al. Stat1 confers sensitivity to radiation in cervical cancer cells by controlling Parp1 levels:a new perspective for Parp1 inhibition[J]. Cell Death Dis,2021,12(10):933.
    [32]
    Thaker PH,Salani R,Brady WE,et al. A phase I trial of paclitaxel,cisplatin,and veliparib in the treatment of persistent or recurrent carcinoma of the cervix:an NRG Oncology Study (NCT#01281852)[J]. Ann Oncol,2017,28(3):505-511.
    [33]
    Yamashita N,Kanno Y,Saito N,et al. Aryl hydrocarbon receptor counteracts pharmacological efficacy of doxorubicin via enhanced AKR1C3 expression in triple negative breast cancer cells[J]. Biochem Biophys Res Commun,2019,516(3):693-698.
    [34]
    Noordermeer SM,Adam S,Setiaputra D,et al. The shieldin complex mediates 53BP1-dependent DNA repair[J]. Nature,2018,560(7716):117-121.
    [35]
    Shi JY,Bai Y,Peng KW,et al. Research progress of PARP-1 inhibitors in combination with other drugs to overcome drug resistance[J]. J China Pharm Univ(中国药科大学学报),2019,50(5):523-530.
    [36]
    Wang SP,Li Y,Huang SH,et al. Discovery of potent and novel dual PARP/BRD4 inhibitors for efficient treatment of pancreatic cancer[J]. J Med Chem,2021,64(23):17413-17435.
    [37]
    Klein FG,Granier C,Zhao YL,et al. Combination of talazoparib and palbociclib as a potent treatment strategy in bladder cancer[J]. J Pers Med,2021,11(5):340.
    [38]
    Johnson SF,Cruz C,Greifenberg AK,et al. CDK12 inhibition reverses de novo and acquired PARP inhibitor resistance in BRCA wild-type and mutated models of triple-negative breast cancer[J]. Cell Rep,2016,17(9):2367-2381.
    [39]
    Fang Y,McGrail DJ,Sun CY,et al. Sequential therapy with PARP and WEE1 inhibitors minimizes toxicity while maintaining efficacy[J]. Cancer Cell,2019,35(6):851-867.
    [40]
    Garcia TB,Snedeker JC,Baturin D,et al. A small-molecule inhibitor of WEE1,AZD1775,synergizes with olaparib by impairing homologous recombination and enhancing DNA damage and apoptosis in acute leukemia[J]. Mol Cancer Ther,2017,16(10):2058-2068.
    [41]
    Tran Chau V,Liu W,Gerbé de Thoré M,et al. Differential therapeutic effects of PARP and ATR inhibition combined with radiotherapy in the treatment of subcutaneous versus orthotopic lung tumour models[J]. Br J Cancer,2020,123(5):762-771.
    [42]
    Ning JF,Stanciu M,Humphrey MR,et al. Myc targeted CDK18 promotes ATR and homologous recombination to mediate PARP inhibitor resistance in glioblastoma[J]. Nat Commun,2019,10(1):2910.
    [43]
    Neeb A,Herranz N,Arce-Gallego S,et al. Advanced prostate cancer with ATM loss:PARP and ATR inhibitors[J]. Eur Urol,2021,79(2):200-211.
    [44]
    Parmar K,Kochupurakkal BS,Lazaro JB,et al. The CHK1 inhibitor prexasertib exhibits monotherapy activity in high-grade serous ovarian cancer models and sensitizes to PARP inhibition[J]. Clin Cancer Res,2019,25(20):6127-6140.
    [45]
    Gralewska P,Gajek A,Marczak A,et al. Participation of the ATR/CHK1 pathway in replicative stress targeted therapy of high-grade ovarian cancer[J]. J Hematol Oncol,2020,13(1):39.
    [46]
    Do KT,Kochupurakkal B,Kelland S,et al. Phase 1 combination study of the CHK1 inhibitor prexasertib and the PARP inhibitor olaparib in high-grade serous ovarian cancer and other solid tumors[J]. Clin Cancer Res,2021,27(17):4710-4716.
    [47]
    Zhang SL,Peng X,Li XF,et al. BKM120 sensitizes glioblastoma to the PARP inhibitor rucaparib by suppressing homologous recombination repair[J]. Cell Death Dis,2021,12(6):546.
    [48]
    Li Y,Wang YT,Zhang WP,et al. BKM120 sensitizes BRCA-proficient triple negative breast cancer cells to olaparib through regulating FOXM1 and Exo1 expression[J]. Sci Rep,2021,11(1):4774.
    [49]
    Cardnell RJ,Feng Y,Diao LX,et al. Proteomic markers of DNA repair and PI3K pathway activation predict response to the PARP inhibitor BMN 673 in small cell lung cancer[J]. Clin Cancer Res,2013,19(22):6322-6328.
    [50]
    Matulonis UA,Wulf GM,Barry WT,et al. Phase I dose escalation study of the PI3kinase pathway inhibitor BKM120 and the oral poly (ADP ribose) polymerase (PARP) inhibitor olaparib for the treatment of high-grade serous ovarian and breast cancer[J]. Ann Oncol,2017,28(3):512-518.
    [51]
    Du Y,Yamaguchi H,Wei YK,et al. Blocking c-Met-mediated PARP1 phosphorylation enhances anti-tumor effects of PARP inhibitors[J]. Nat Med,2016,22(2):194-201.
    [52]
    Meng JY,Peng J,Feng J,et al. Niraparib exhibits a synergistic anti-tumor effect with PD-L1 blockade by inducing an immune response in ovarian cancer[J]. J Transl Med,2021,19(1):415.
    [53]
    Jiao SP,Xia WY,Yamaguchi H,et al. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression[J]. Clin Cancer Res,2017,23(14):3711-3720.
    [54]
    Wang YL,Zheng K,Xiong H,et al. PARP inhibitor upregulates PD-L1 expression and provides a new combination therapy in pancreatic cancer[J]. Front Immunol,2021,12:762989.
    [55]
    Konstantinopoulos PA,Waggoner S,Vidal GA,et al. Single-arm phases 1 and 2 trial of niraparib in combination with pembrolizumab in patients with recurrent platinum-resistant ovarian carcinoma[J]. JAMA Oncol,2019,5(8):1141-1149.
    [56]
    Domchek SM,Postel-Vinay S,Im SA,et al. Olaparib and durvalumab in patients with germLine BRCA-mutated metastatic breast cancer (MEDIOLA):an open-label,multicentre,phase 1/2,basket study[J]. Lancet Oncol,2020,21(9):1155-1164.
    [57]
    Bizzaro F,Fuso Nerini I,Taylor MA,et al. VEGF pathway inhibition potentiates PARP inhibitor efficacy in ovarian cancer independent of BRCA status[J]. J Hematol Oncol,2021,14(1):186.
    [58]
    Lheureux S,Oaknin A,Garg S,et al. EVOLVE:a multicenter open-label single-arm clinical and translational phase II trial of cediranib plus olaparib for ovarian cancer after PARP inhibition progression[J]. Clin Cancer Res,2020,26(16):4206-4215.
    [59]
    Mirza MR,?vall Lundqvist E,Birrer MJ,et al. Niraparib plus bevacizumab versus niraparib alone for platinum-sensitive recurrent ovarian cancer (NSGO-AVANOVA2/ENGOT-ov24):a randomised,phase 2,superiority trial[J]. Lancet Oncol,2019,20(10):1409-1419.
    [60]
    Pratz KW,Rudek MA,Gojo I,et al. A phase I study of topotecan,carboplatin and the PARP inhibitor veliparib in acute leukemias,aggressive myeloproliferative neoplasms,and chronic myelomonocytic leukemia[J]. Clin Cancer Res,2017,23(4):899-907.
    [61]
    LoRusso PM,Li J,Burger A,et al. Phase I safety,pharmacokinetic,and pharmacodynamic study of the poly(ADP-ribose) polymerase (PARP) inhibitor veliparib (ABT-888) in combination with irinotecan in patients with advanced solid tumors[J]. Clin Cancer Res,2016,22(13):3227-3237.
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