PARP inhibitors in ovarian cancer therapy
DOI:
https://doi.org/10.56782/pps.185Abstract
Ovarian cancer is responsible for the highest number of deaths of all female genital cancers. It is ranked as the sixth in the incidence and fourth in the mortality rate of malignant tumours in women in Poland. The disease is initially asymptomatic, which is why it is usually detected at advanced stages. More than 70% of ovarian cancer cases are detected at the stage III or IV according to the FIGO classification. The treatment of ovarian cancer is mainly based on surgery combined with systemic treatment (chemotherapy based on platinum derivatives and taxanes). Although most patients achieve a good response to first-line chemotherapy, there is usually a recurrence and drug resistance at a later stage, and the prognosis for recurrence is poor. PARP (Poly ADP-ribose polymerase) inhibitors are a new class of oral anticancer drugs that target DNA repair pathways and have shown promising efficacy in ovarian cancer patients in recent clinical trials. Olaparib, rucaparib and niraparib are innovative drugs currently changing clinical practice in ovarian cancer patients.
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Didkowska, J.A.; Wojciechowska, U., Barańska, K.; Miklewska, M.; Michałek, I.; Olasek, P. Nowotwory złośliwe w Polsce w 2021 roku. Raport roczny. Narodowy Instytut Onkologii. Krajowy Rejestr Nowotworów. Warszawa 2023. ISSN 0867-8251
Basta, A. et al., Recommendations of the Polish Gynecological Oncology Society for the diagnosis and treatment of ovarian cancer. Curr. Gyn. Oncol. 2017, 15, 5-23. DOI: https://doi.org/10.15557/CGO.2017.0001
Jassem, J.; Kordek, R. Onkologia. Podręcznik dla studentów i lekarzy. Ed. 5. 2019. Via Medica. 243-249
Zheng, F. et al. Mechanism and current progress of Poly ADP-ribose polymerase (PARP) inhibitors in the treatment of ovarian cancer. Biomed. Pharmacother. 2020, 123, Art. No: 109661. doi: 10.1016/j.biopha.2019.10966 DOI: https://doi.org/10.1016/j.biopha.2019.109661
Herceg, Z.; Wang, Z.-Q. Functions of poly(ADP-ribose)polymerase (PARP) in DNA repair, genomic integrity and cell death. Mutat. Res. 2001, 477(1-2), 97-110. doi: 10.1016/s0027-5107(01)00111-7. DOI: https://doi.org/10.1016/S0027-5107(01)00111-7
Lindahl, T. Instability and decay of the primary structure of DNA. Nature 1993, 362(6422), 709-715. doi: 10.1038/362709a0 DOI: https://doi.org/10.1038/362709a0
Hoeijmakers, J.H., Genome maintenance mechanisms for preventing cancer. Nature 2001, 411(6835), 366-74. doi: 10.1038/35077232 DOI: https://doi.org/10.1038/35077232
Foo, T.; George, A.; Banerjee, S. PARP inhibitors in ovarian cancer: An overview of the practice-changing trials. Genes Chromosomes Cancer 2021, 60(5), 385-397. doi: 10.1002/gcc.22935 DOI: https://doi.org/10.1002/gcc.22935
Smith, M.; Pothuri, B. Appropriate Selection of PARP Inhibitors in Ovarian Cancer. Curr. Treat. Options Oncol. 2022, 23(6), 887-903. doi: 10.1007/s11864-022-00938-4 DOI: https://doi.org/10.1007/s11864-022-00938-4
Lynparza Product Information. European Medicines Agency.
Paulino, E. Lessons learned with a longer follow-up from SOLO 1. J. Gynecol. Oncol. 2023, 34(1), Art. No: e29. doi: 10.3802/jgo.2023.34.e29 DOI: https://doi.org/10.3802/jgo.2023.34.e29
Pujade-Lauraine, E. et al. Olaparib tablets as maintenance therapy in patients with platinum sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017, 18(9), 1274-1284. doi: 10.1016/S1470-2045(17)30469-2 DOI: https://doi.org/10.1016/S1470-2045(17)30469-2
Ray-Coquard, I. et al., Olaparib plus Bevacizumab as First-Line Maintenance in Ovarian Cancer. N. Engl. J. Med. 2019, 381(25), 2416-2428. doi: 10.1056/NEJMoa1911361 DOI: https://doi.org/10.1056/NEJMoa1911361
Rubraca Product Information. European Medicines Agency.
Coleman, R.L. et al. Rucaparib maintenance treatment for recurrent ovarian carcinoma after response to platinum therapy (ARIEL3): a randomised, doubleblind, placebo-controlled, phase 3 trial. Lancet 2017, 390(10106), 1949-1961. doi: 10.1016/S0140-6736(17)32440-6 DOI: https://doi.org/10.1016/S0140-6736(17)32440-6
Monk, B.J. et al. A Randomized, Phase III Trial to Evaluate Rucaparib Monotherapy as Maintenance Treatment in Patients With Newly Diagnosed Ovarian Cancer (ATHENA-MONO/GOG-3020/ENGOT-ov45). J. Clin. Oncol. 2022, 40(34), 3952-3964. doi: 10.1200/JCO.22.01003 DOI: https://doi.org/10.1200/JCO.22.01003
Zejula Product Information. European Medicines Agency.
González-Martín, A. et al. Niraparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. N. Engl. J. Med. 2019, 381(25), 2391-2402. doi: 10.1056/NEJMoa1910962 DOI: https://doi.org/10.1056/NEJMoa1910962
Mirza, M.R. et al. Niraparib Maintenance Therapy in Platinum-Sensitive, Recurrent Ovarian Cancer. N. Engl. J. Med. 2016, 375(22), 2154-2164. doi: 10.1056/NEJMoa1611310. DOI: https://doi.org/10.1056/NEJMoa1611310
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