PARP Inhibitor for Ovarian Cancer Therapy

I Nyoman Bayu Mahendra; William Alexander Setiawan

doi:10.24018/ejmed.2022.4.6.1477

I Nyoman Bayu Mahendra

William Alexander Setiawan

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Submitted Aug 10, 2022
Published Nov 9, 2022

10.24018/ejmed.2022.4.6.1477

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Abstract

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.

Keywords: EOC, PARP, Olaparib

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References

Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7-30.
DOI | Google Scholar

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

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

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

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

Ang YLE, Tan DSP. Development of PARP inhibitors in gynecological malignancies. Curr Probl Cancer. 2017; 41(4): 273-286.
DOI | Google Scholar

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007; 25(11): 1329-33.
DOI | Google Scholar

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

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

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

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

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

Kaelin WJ. The concept of synthetic lethality in the context of anticancer therapy, Nat. Rev. Cancer. 2005; 5(9): 689-698.
DOI | Google Scholar

Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature. 2001; 411(6835): 366-374.
DOI | Google Scholar

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

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

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

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Mahendra, I. N. B., & Setiawan, W. A. (2022). PARP Inhibitor for Ovarian Cancer Therapy. European Journal of Medical and Health Sciences, 4(6), 1–7. https://doi.org/10.24018/ejmed.2022.4.6.1477

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Vol. 4 No. 6 (2022)

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[1] Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin. 2017; 67(1): 7-30.
DOI | Google Scholar

[2] 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

[3] 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

[4] 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

[5] 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

[6] Ang YLE, Tan DSP. Development of PARP inhibitors in gynecological malignancies. Curr Probl Cancer. 2017; 41(4): 273-286.
DOI | Google Scholar

[7] 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

[8] 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

[9] 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

[10] 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

[11] 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

[12] 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

[13] 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

[14] 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

[15] 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

[16] 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

[17] 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

[18] 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

[19] 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

[20] 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

[21] Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clin Oncol. 2007; 25(11): 1329-33.
DOI | Google Scholar

[22] 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

[23] 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

[24] 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

[25] 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

[26] 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

[27] Kaelin WJ. The concept of synthetic lethality in the context of anticancer therapy, Nat. Rev. Cancer. 2005; 5(9): 689-698.
DOI | Google Scholar

[28] Hoeijmakers J. Genome maintenance mechanisms for preventing cancer. Nature. 2001; 411(6835): 366-374.
DOI | Google Scholar

[29] 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

[30] 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

[31] 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

PARP Inhibitor for Ovarian Cancer Therapy

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