PARP Inhibitor for Ovarian Cancer Therapy
Article Main Content
Almost all ovarian cancers are comprised of epithelial ovarian cancer (EOC). Approximately 80% of patients with EOC initially respond to standard cytoreductive therapy and postoperative platinum-based chemotherapy. However, due to drug resistance in high-grade serous ovarian cancer (HGSOC), recurrence is almost inevitable. Recently, the nuclear enzyme poly (ADP ribose) polymerase (PARP) represents a surprisingly new target in EOC therapy. Inhibitors of PARP have demonstrated promising efficacy in the treatment of EOC. Studies on Olaparib, in particular, hastened its approval in the USA and Europe. The main topics of this study are the pre-clinical evidence, ongoing clinical studies, recent advancements in PARP inhibitor technology, and their potential future roles in clinical care for EOC patients.
References
-
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7-30.
DOI |
Google Scholar
1
-
George SH, Garcia R, Slomovitz BM. Ovarian Cancer: The Fallopian Tube as the Site of Origin and Opportunities for Prevention. Front Oncol. 2016; 6: 108.
DOI |
Google Scholar
2
-
Papa A, Caruso D, Strudel M, Tomao S, Tomao F. Update on Poly-ADP-ribose polymerase inhibition for ovarian cancer treatment. J Transl Med. 2016; 14: 267.
DOI |
Google Scholar
3
-
Karakasis K, Burnier JV, Bowering V, Oza AM, Lheureux S. Ovarian Cancer and BRCA1/2 Testing: Opportunities to Improve Clinical Care and Disease Prevention. Front Oncol. 2016; 6: 119.
DOI |
Google Scholar
4
-
Banerjee S, Kaye SB. New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin Cancer Res. 2013; 19(5): 961-8.
DOI |
Google Scholar
5
-
Ang YLE, Tan DSP. Development of PARP inhibitors in gynecological malignancies. Curr Probl Cancer. 2017; 41(4): 273-286.
DOI |
Google Scholar
6
-
Gibson BA, Kraus WL. New insights into the molecular and cellular functions of poly(ADP-ribose) and PARPs. Nat Rev Mol Cell Biol. 2012; 13(7): 411-24.
DOI |
Google Scholar
7
-
George A, Kaye S, Banerjee S. Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer. Nat Rev Clin Oncol. 2017; 14(5): 284-296.
DOI |
Google Scholar
8
-
Scott CL, Swisher EM, Kaufmann SH. Poly (ADP-ribose) polymerase inhibitors: recent advances and future development, J. Clin. Oncol. 2015; 33(12): 1397-1406.
DOI |
Google Scholar
9
-
Langelier MF, Servent KM, Rogers EE, Pascal JM. A third zinc-binding domain of human poly(ADP-ribose) polymerase-1 coordinates DNA-dependent enzyme activation. J Biol Chem. 2008; 283(7): 4105-14.
DOI |
Google Scholar
10
-
Tao Z, Gao P, Hoffman DW, Liu HW. Domain C of human poly(ADP-ribose) polymerase-1 is important for enzyme activity and contains a novel zinc-ribbon motif. Biochemistry. 2008; 47(21): 5804-13.
DOI |
Google Scholar
11
-
Plummer R. Perspective on the pipeline of drugs being developed with modulation of DNA damage as a target. Clin Cancer Res. 2010; 16(18): 4527-31.
DOI |
Google Scholar
12
-
Chen Y, Zhang L, Hao Q. Olaparib: a promising PARP inhibitor in ovarian cancer therapy. Arch Gynecol Obstet. 2013; 288(2): 367-74.
DOI |
Google Scholar
13
-
Davar D, Beumer JH, Hamieh L, Tawbi H. Role of PARP inhibitors in cancer biology and therapy. Curr Med Chem. 2012; 19(23): 3907-21.
DOI |
Google Scholar
14
-
Sonnenblick A, de Azambuja E, Azim HA Jr, Piccart M. An update on PARP inhibitors--moving to the adjuvant setting. Nat Rev Clin Oncol. 2015; 12(1): 27-41.
DOI |
Google Scholar
15
-
Gudmundsdottir K, Ashworth A. The roles of BRCA1 and BRCA2 and associated proteins in the maintenance of genomic stability. Oncogene. 2006; 25(43): 5864-74.
DOI |
Google Scholar
16
-
Jones P, Wilcoxen K, Rowley M, Toniatti C. Niraparib: A Poly(ADP-ribose) Polymerase (PARP) Inhibitor for the Treatment of Tumors with Defective Homologous Recombination. J Med Chem. 2015; 58(8): 3302-14.
DOI |
Google Scholar
17
-
Hall JM, Lee MK, Newman B, Morrow JE, Anderson LA, Huey B, et al. Linkage of early-onset familial breast cancer to chromosome 17q21. Science. 1990; 250(4988): 1684-9.
DOI |
Google Scholar
18
-
Wooster R, Neuhausen SL, Mangion J, Quirk Y, Ford D, Collins N, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994; 265(5181): 2088-90.
DOI |
Google Scholar
19
-
Audeh MW. Novel treatment strategies in triple-negative breast cancer: specific role of poly(adenosine diphosphate-ribose) polymerase inhibition. Pharmgenomics Pers Med. 2014; 7: 307-16.
DOI |
Google Scholar
20
-
Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007; 25(11): 1329-33.
DOI |
Google Scholar
21
-
Risch HA, McLaughlin JR, Cole DE, Rosen B, Bradley L, Kwan E, et al. Prevalence and penetrance of germline BRCA1 and BRCA2 mutations in a population series of 649 women with ovarian cancer. Am J Hum Genet. 2001; 68(3): 700-10.
DOI |
Google Scholar
22
-
Alsop K, Fereday S, Meldrum C, deFazio A, Emmanuel C, George J, et al. BRCA mutation frequency and patterns of treatment response in BRCA mutation-positive women with ovarian cancer: a report from the Australian Ovarian Cancer Study Group. J Clin Oncol. 2012; 30(21): 2654-63
DOI |
Google Scholar
23
-
Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB, et al. Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature. 2005; 434(7035): 917-21.
DOI |
Google Scholar
24
-
Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E, et al. Specific killing of BRCA2-deficient tumors with inhibitors of poly(ADP-ribose) polymerase. Nature. 2005; 434(7035): 913-7.
DOI |
Google Scholar
25
-
Evans U. Matulonis, PARP inhibitors in ovarian cancer: evidence, experience and clinical potential, Ther. Adv. Med. Oncol. 2017; 9(4): 253-267.
DOI |
Google Scholar
26
-
Kaelin WJ. The concept of synthetic lethality in the context of anticancer therapy, Nat. Rev. Cancer. 2005; 5(9): 689-698.
DOI |
Google Scholar
27
-
Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature. 2001; 411(6835): 366-374.
DOI |
Google Scholar
28
-
Loveday C, Turnbull C, Ramsay E, Hughes D, Ruark E, Frankum JR, et al. Germline mutations in RAD51D confer susceptibility to ovarian cancer. Nat Genet. 2011; 43(9): 879-882.
DOI |
Google Scholar
29
-
Bajrami I, Frankum JR, Konde A, Miller RE, Rehman FL, Brough R, et al. Genome-wide profiling of genetic synthetic lethality identifies CDK12 as a novel determinant of PARP1/2 inhibitor sensitivity. Cancer Res. 2014; 74(1): 287-297.
DOI |
Google Scholar
30
-
Ke Y, Zhang J, Lv X, Zeng X, Ba X. Novel insights into PARPs in gene expression: regulation of RNA metabolism. Cell Mol Life Sci. 2019; 76(17): 3283-3299.
DOI |
Google Scholar
31
Most read articles by the same author(s)
-
Evert Solomon Pangkahila,
William Alexander Setiawan,
Type 1 Diabetes in Pregnancy: A Review , European Journal of Medical and Health Sciences: Vol. 4 No. 4 (2022) -
I Nyoman Hariyasa Sanjaya,
Tjokorda Gde Agung Suwardewa,
Anak Agung Ngurah Jaya Kusuma,
Ryan Saktika Mulyana,
Evert Solomon Pangkahila,
William Alexander Setiawan,
Meconium Peritonitis , European Journal of Medical and Health Sciences: Vol. 4 No. 5 (2022) -
I Made Darmayasa,
Made Bagus Dwi Aryana,
William Alexander Setiawan,
Gede Eka Rusdi Antara,
Gossypiboma Post Cesarean Section: Patient Safety Review , European Journal of Medical and Health Sciences: Vol. 5 No. 5 (2023) -
I Nyoman Hariyasa Sanjaya,
Ryan Saktika Mulyana,
Evert Solomon Pangkahila,
Cokorda Istri Mirayani Pemayun,
William Alexander Setiawan,
Pregnancy with Prolapse Utery , European Journal of Medical and Health Sciences: Vol. 5 No. 2 (2023) -
I Nyoman Hariyasa Sanjaya,
Ryan Saktika Mulyana,
Evert Solomon Pangkahila,
Cokorda Istri Mirayani Pemayun,
William Alexander Setiawan,
Fetal Megacystic Spontaneus Resolution: A Case Report , European Journal of Medical and Health Sciences: Vol. 5 No. 2 (2023) -
I Made Darmayasa,
William Alexander Setiawan,
Wati Evilia,
Feby Ubro,
Psycho-Social Impact of Stigmatization against Pregnant Women with HIV , European Journal of Medical and Health Sciences: Vol. 5 No. 4 (2023) -
Ida Bagus Putra Praja Adnyana,
I Gusti Ngurah Bagus Surya Udayana,
Made Angga Diningrat,
William Alexander Setiawan,
Fertility, Pregnancy Rate, and Neonatal Outcome of Patient with Adenomyosis , European Journal of Medical and Health Sciences: Vol. 4 No. 5 (2022) -
I Gde Sastra Winata,
William Alexander Setiawan,
I Kadek Wahyu Putra Dyatmika,
I Gede Agus Rastika,
Shaalini Arjunan,
Twin to Twin Transfusion Syndrome in Discordance Twins: Diagnostic and Management Approach , European Journal of Medical and Health Sciences: Vol. 5 No. 2 (2023) -
I Made Darmayasa,
William Alexander Setiawan,
Ni Wayan Kertiasih,
Gede Vasmana Hardika,
Existential Psychotherapy to Improve the Meaningfulness of Life in Advanced Stage of Cervical Cancer Patients: A Case Study , European Journal of Medical and Health Sciences: Vol. 5 No. 5 (2023) -
I Nyoman Bayu Mahendra,
I Nyoman Gede Budiana,
I Gede Mega Putra,
Ryan Saktika Mulyana,
I Gde Sastra Winata,
Budi Setiawan Harjoto,
E6/E7 Oncogenes Mutation of Human Papillomavirus Type 16 Associated with P16 Protein Expression in Cervical Cancer , European Journal of Medical and Health Sciences: Vol. 5 No. 2 (2023)