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Journal of Education, Health and Sport

Targeted therapy with Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of solid tumours
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Targeted therapy with Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of solid tumours

Authors

  • Faustyna Piędel Faculty of Medicine, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin https://orcid.org/0000-0002-8280-498X
  • Agata Agnieszka Rocka Faculty of Medicine, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin https://orcid.org/0000-0003-4738-3160
  • Klaudia Daria Szumna Faculty of Medicine, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin https://orcid.org/0000-0002-0889-2627
  • Dominika Katarzyna Madras Faculty of Medicine, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin https://orcid.org/0000-0002-1777-4403
  • Patryk Piotr Jasielski Faculty of Medicine, Medical University of Lublin, Chodźki Street 19, 20-093 Lublin https://orcid.org/0000-0002-0958-735X

DOI:

https://doi.org/10.12775/JEHS.2020.10.03.014

Keywords

Targeted Molecular Therapy, Poly(ADP-ribose) Polymerase Inhibitors, BRCA1 Gene, Triple Negative Breast Neoplasms

Abstract

Introduction: According to the National Cancer Register in Poland, the number of cancers including breast cancers has more than doubled in the past three decades. Poly(ADP-ribose) polymerase (PARP) inhibitors lead to the death of cells with a BRCA1/2 mutation. The use of PARP inhibitors has increased significantly over the last 5 years.

Objective: This article summarizes the current knowledge about the safety and clinical  efficacy of PARP inhibitors in the treatment of solid tumors.

Abbreviated description of the state of knowledge: PARP inhibitors have been used in the standard treatment of ovarian cancer. Three of them: Olaparyb, Rucaparyb and Niraparyb have indications for maintenance treatment in recurrent platinum-sensitive ovarian cancer. Olaparib and Weliparib are used to treat breast cancer patients. Research shows that the use of Olaparib in breast cancer patients has reduced tumours size as much as around 60% of women with BRCA mutation. The combination of veloparin with carbolatin and paclitaxel was associated with a longer mean survival period than chemotherapy alone in treatment of non-small cell lung cancer(NSCLC).

In addition, there are studies showing the benefits of PARP inhibitor therapy in prostate cancer. Olaparyb in combination with abiraterone shows greater clinical efficacy in patients with castration-resistant prostate cancer compared alone abiraterone.

Conclusions: FDA approval of new PARP inhibitors is a promising method for more effective treatment of the most common cancers in the world. In the future further research may lead to a better definition of the patient group benefiting most from PARP inhibitor therapy. 

References

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Kukolj E, Kaufmann T, Dick AE, Zeillinger R, Gerlich DW, Slade D. PARP inhibition causes premature loss of cohesion in cancer cells. Oncotarget. 2017;8(61):103931-103951.

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Neviere Z, De La Motte Rouge T, Floquet A, Johnson A, Berthet P, Joly F. How and when to refer patients for oncogenetic counseling in the era of PARP inhibitors. Ther Adv Med Oncol. 2020;12:1758835919897530.

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http://onkologia.org.pl/wpcontent/uploads/Nowotwory_2016.pdf?fbclid=IwAR3dDcDW9fNy9C6eMl94UqItO9Bg9rjGaEg4G0ZfoLyBJ4ayIHm3U8_vqKw

(dostęp: 2020.03.19)

Kurnit KC, Coleman RL, Westin SN. Using PARP Inhibitors in the Treatment of Patients With Ovarian Cancer.Curr Treat Options Oncol. 2018;19(12):1.

Armstrong DK.New Therapies for Ovarian Cancer. JNCCN. 2018;16:5S.

Geenen JJJ, Linn SC, Beijnen JH, Schellens JHM.;PARP Inhibitors in the Treatment of Triple-Negative Breast Cancer. Clin Pharmacokinet. 2018 Apr;57(4):427-437.

Rugo HS, Olopade OI, DeMichele A, Yau C, van 't Veer LJ, Buxton MB et al. Adaptive Randomization of Veliparib-Carboplatin Treatment in Breast Cancer. N Engl J Med. 2016;375(1):23-34.

Gelmon KA, Tischkowitz M, Mackay H, Swenerton K, Robidoux A, Tonkin K et al., Olaparib in patients with recurrent high-grade serous or poorly differentiated ovarian carcinoma or triple-negative breast cancer: a phase 2, multicentre, open-label, non-randomised study, Lancet Oncol. 2011;12(9):852-61.

Olaparib Keeps Hereditary Breast Tumors in Check. Cancer Discov. 2017;7(8):OF10.https://cancerdiscovery.aacrjournals.org/content/7/8/OF10.long (dostęp: 2020.03.21)

Rodler ET, Kurland BF, Griffin M, Gralow JR, Porter P, Yeh RF et al. Phase I Study of Veliparib (ABT-888) Combined with Cisplatin and Vinorelbine in Advanced Triple-Negative Breast Cancer and/or BRCA Mutation-Associated Breast Cancer. Clin Cancer Res. 2016;22(12):2855-64.

Jiang Y, Dai H, Li Y, Yin J, Guo S, Lin SY et al. PARP inhibitors synergize with gemcitabine by potentiating DNA damage in non-small-cell lung cancer. Int J Cancer. 2019;144(5):1092-1103.

Rossi G, Zullo L, Cerbone L, Coco S, Longo L, Tagliamento M et al. ADP ribose polymerase inhibitors for treating non-small cell lung cancer: new additions to the pharmacotherapeutic armamentarium.Expert Opin Pharmacother.2020.1-8.

Ramalingam SS, Blais N, Mazieres J, Reck M, Jones CM, Juhasz E et al. Randomized, Placebo-Controlled, Phase II Study of Veliparib in Combination with Carboplatin and Paclitaxel for Advanced/Metastatic Non-Small Cell Lung Cancer. Clin Cancer Res. 2017;23(8):1937-1944.

Grasso CS, Wu YM, Robinson DR, Cao X, Dhanasekaran SM, Khan AP et al. The mutational landscape of lethal castration-resistant prostate cancer. Nature. 2012;487(7406):239-43.

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;434:917–921.

Clarke N, Wiechno P, Alekseev B, Sala N, Jones R, Kocak I et al. Olaparib combined with abiraterone in patients with metastatic castration-resistant prostate cancer: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol. 2018 Jul;19(7):975-986.

Mateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R et al. DNA-repair defects and olaparib in metastatic prostate cancer. N Engl J Med. 2015;373(18):1697–708.

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Published

2020-03-27

How to Cite

1.
PIĘDEL, Faustyna, ROCKA, Agata Agnieszka, SZUMNA, Klaudia Daria, MADRAS, Dominika Katarzyna and JASIELSKI, Patryk Piotr. Targeted therapy with Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of solid tumours. Journal of Education, Health and Sport. Online. 27 March 2020. Vol. 10, no. 3, pp. 133-139. [Accessed 6 July 2025]. DOI 10.12775/JEHS.2020.10.03.014.
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Vol. 10 No. 3 (2020)

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Review Articles

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