Estrategias terapéuticas actuales en el tratamiento del cáncer de ovario

Carmita Lemus-Valdés, Alejandro Padrón-Albertus

Resumen

Introducción: el cáncer de ovario es uno de los tumores más frecuentes y letales entre las mujeres. Esto se debe a su detección en estados tardíos y al desarrollo de quimiorresistencia a la terapia estándar. El desarrollo de terapias dirigidas contra las propiedades distintivas de las células cancerosas y sus características habilitadoras ha surgido como una alternativa promisoria para el tratamiento de estos tumores.

Objetivo: describir las actuales estrategias terapéuticas dirigidas contra las distintas capacidades de las células tumorales en el tratamiento del cáncer de ovario.

Método: se realizó una búsqueda en las bases de datos ScienceDirect, Redalyc, Latindex, ResearchGate, PubMed, Elsevier, ClinicalTrials.gov, SpringerLink, LARVOL´s CLIN, Registro Público Cubano de Ensayos Clínicos, entre enero y abril de 2023. Se seleccionaron 50 artículos referentes al cáncer de ovario y las alternativas para su tratamiento.

Desarrollo: se mencionaron los diversos factores que influyen en la elección de terapias contra el cáncer de ovario. Se describieron las actuales dianas terapéuticas utilizadas en el tratamiento de esta neoplasia, así como el empleo de múltiples fármacos aprobados y en fases de estudio, y las combinaciones sinérgicas de los mismos.

Consideraciones finales: actualmente existen disímiles opciones de tratamiento del cáncer de ovario. A pesar de que la eficacia clínica de los agentes dirigidos todavía está restringida a subtipos moleculares específicos y ningún ensayo ilustra un beneficio en la supervivencia general, son notorios los resultados alcanzados en el desarrollo de fármacos específicamente dirigidos contra la inestabilidad del genoma y angiogénesis sostenida.

Palabras clave

cáncer de ovario; cáncer epitelial de ovario; fármaco antitumoral; quimiorresistencia; terapia molecular dirigida

Referencias

Seyfried TN, Shelton LM. Cancer as a metabolic disease. Nutr Metab (Lond) [Internet]. 2010 [citado 22 Feb 2023]; 7(1):7. DOI: http://dx.doi.org/10.1186/1743-7075-7-7

Momenimovahed Z, Tiznobaik A, Taheri S, Salehiniya H. Ovarian cancer in the world: epidemiology and risk factors. Int J Womens Health [Internet]. 2019 [citado 22 Feb 2023]; 11:287-99. DOI: http://dx.doi.org/10.2147/IJWH.S197604

Novoa-Vargas A. Historia natural del cáncer de ovario. Ginecol Obstet Mex [Internet]. 2014 [citado 22 Feb 2023]; 82(09):613-22. Disponible en: https://www.medigraphic.com/cgi-bin/new/resumen.cgi?IDARTICULO=52473

Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin [Internet]. 2021 [citado 22 Feb 2023]; 71(3):209-49. DOI: http://dx.doi.org/10.3322/caac.21660

Dirección de Registros Médicos y Estadísticas de la Salud. Anuario Estadístico de Salud 2021 [Internet]. La Habana: Ministerio de Salud Pública; 2022 [citado 21 Abr 2023]. Disponible en: https://temas.sld.cu/estadisticassalud/

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell [Internet]. 2000 [citado 22 Feb 2023]; 100(1):57-70. Disponible en: https://www.cell.com/fulltext/S0092-8674(00)81683-9?fbclid=IwAR0F_uCcj4O8k6YFd1jNj7K5HXbc3_8sB42NgSE-PcD8Ekg94mOcWpmJWcM

Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell [Internet]. 2011 [citado 22 Feb 2023]; 144(5):646-74. Disponible en: https://www.sciencedirect.com/science/article/pii/S0092867411001279

Hanahan D. Hallmarks of cancer: New dimensions. Cancer Discov [Internet]. 2022 [citado 22 Feb 2023]; 12(1):31-46. Disponible en: https://aacrjournals.org/cancerdiscovery/article/12/1/31/675608/Hallmarks-of-Cancer-New-DimensionsHallmarks-of

Meinhold-Heerlein I, Hauptmann S. The heterogeneity of ovarian cancer. Arch Gyn Obst [Internet]. 2014 [citado 22 Feb 2023]; 289(2):237-9. DOI: http://dx.doi.org/10.1007/s00404-013-3114-3

Ghoneum A, Afify H, Salih Z, Kelly M, Said N. Role of tumor microenvironment in the pathobiology of ovarian cancer: Insights and therapeutic opportunities. Cancer Med [Internet]. 2018 [citado 22 Feb 2023]; 7(10):5047-56. Doi: http://dx.doi.org/10.1002/cam4.1741

Mota A, S Oltra S, Moreno-Bueno G. Insight updating of the molecular hallmarks in ovarian carcinoma. EJC Suppl [Internet]. 2020 [citado 22 Feb 2023]; 15:16-26. Disponible en: https://www.sciencedirect.com/science/article/pii/S1359634919300011

Rendi MH. Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Histopathology [Internet]. UpToDate. 2022 [citado 22 Feb 2023]. Disponible en: https://www.medilib.ir/uptodate/show/3241

Gong X, Chi H, Strohmer DF, Teichmann AT, Xia Z, Wang Q. Exosomes: A potential tool for immunotherapy of ovarian cancer. Front Immunol [Internet]. 2022 [citado 29 Abr 2023]; 13:1089410. DOI: http://dx.doi.org/10.3389/fimmu.2022.1089410

Chandra A, Pius C, Nabeel M, Nair M, Vishwanatha JK, Ahmad S, et al. Ovarian cancer: Current status and strategies for improving therapeutic outcomes. Cancer Med [Internet]. 2019 [citado 22 Feb 2023]; 8(16):7018-31. DOI: http://dx.doi.org/10.1002/cam4.2560

Cortez AJ, Tudrej P, Kujawa KA, Lisowska KM. Advances in ovarian cancer therapy. Cancer Chemother Pharmacol [Internet]. 2018 [citado 22 Feb 2023]; 81(1):17-38. DOI: http://dx.doi.org/10.1007/s00280-017-3501-8

Basta A, Bidziński M, Bieńkiewicz A, Blecharz P, Bodnar L, Jach R, et al. Recommendation of the Polish Society of Oncological Gynaecology on the diagnosis and treatment of epithelial ovarian cancer. Oncol Clin Pract [Internet]. 2015 [citado 22 Feb 2023]; 11(5):233-43. Disponible en: https://journals.viamedica.pl/oncology_in_clinical_practice/article/view/44800/36018

Guo T, Dong X, Xie S, Zhang L, Zeng P, Zhang L. Cellular mechanism of gene mutations and potential therapeutic targets in ovarian cancer. Cancer Manag Res [Internet]. 2021 [citado 22 Feb 2023]; 13:3081-100. DOI: http://dx.doi.org/10.2147/CMAR.S292992

Mirza MR, Coleman RL, González-Martín A, Moore KN, Colombo N, Ray-Coquard I, et al. The forefront of ovarian cancer therapy: update on PARP inhibitors. Ann Oncol [Internet]. 2020 [citado 22 Feb 2023]; 31(9):1148-59. Disponible en: https://www.sciencedirect.com/science/article/pii/S0923753420398914

Gershenson DM. Ovarian germ cell tumors: Pathology, epidemiology, clinical manifestations, and diagnosis. www.medilib.ir. 2022 [citado 22 Feb 2023]. Disponible en: https://www.medilib.ir/uptodate/show/3236

Esim O, Hascicek C, Gedik ME, Gunaydin G, Dogan AL. Carboplatin and decitabine loaded lipid-coated albumin nanoparticles for an efficient treatment of platinum-resistant ovarian cancer. J Drug Deliv Sci Technol [Internet]. 2022 [citado 29 Abr 2023]; 76(103801):103801. Disponible en: https://www.sciencedirect.com/science/article/pii/S1773224722007122

Akter S, Rahman MA, Hasan MN, Akhter H, Noor P, Islam R, et al. Recent advances in ovarian cancer: Therapeutic strategies, potential biomarkers, and technological improvements. Cells [Internet]. 2022 [citado 22 Feb 2023]; 11(4):650. Disponible en: https://www.mdpi.com/2073-4409/11/4/650

Cheung A, Bax HJ, Josephs DH, Ilieva KM, Pellizzari G, Opzoomer J, et al. Targeting folate receptor alpha for cancer treatment. Oncotarget [Internet]. 2016 [citado 22 Feb 2023]; 7(32):52553-74. DOI: http://dx.doi.org/10.18632/oncotarget.9651

Sato S, Itamochi H. Profile of farletuzumab and its potential in the treatment of solid tumors. Onco Targets Ther [Internet]. 2016 [citado 22 Feb 2023]; 9:1181-8. DOI: http://dx.doi.org/10.2147/OTT.S98242

Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H, et al. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: Results from the SORAYA study. J Clin Oncol [Internet]. 2023 [citado 29 Abr 2023]; 41(13):2436-45. DOI: http://dx.doi.org/10.1200/JCO.22.01900

Richardson D, Hamilton E, Barve M, Anderson C, Taylor S, Lakhani N, et al. Updated results from the phase 1 expansion study of upifitamab rilsodotin (UpRi; XMT-1536), a NaPi2b-directed dolaflexin antibody drug conjugate (ADC) in ovarian cancer (076). Gyn Oncol [Internet]. 2022 [citado 29 Abr 2023]; 166:S48. DOI: http://dx.doi.org/10.1016/s0090-8258(22)01294-x

Mabuchi S, Kuroda H, Takahashi R, Sasano T. The PI3K/AKT/mTOR pathway as a therapeutic target in ovarian cancer. Gyn Oncol [Internet]. 2015 [citado 22 Feb 2023]; 137(1):173-9. Disponible en: https://www.gynecologiconcology-online.net/article/S0090-8258(15)00606-X/fulltext

Ediriweera MK, Tennekoon KH, Samarakoon SR. Role of the PI3K/AKT/mTOR signaling pathway in ovarian cancer: Biological and therapeutic significance. Semin Cancer Biol [Internet]. 2019 [citado 22 Feb 2023]; 59:147-60. Disponible en: https://www.sciencedirect.com/science/article/pii/S1044579X18301779

Janku F, Yap TA, Meric-Bernstam F. Targeting the PI3K pathway in cancer: are we making headway? Nat Rev Clin Oncol [Internet]. 2018 [citado 22 Feb 2023]; 15(5):273-91. Disponible en: https://www.nature.com/articles/nrclinonc.2018.28

Rinne N, Christie EL, Ardasheva A, Kwok CH, Demchenko N, Low C, et al. Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer. Canc Drug Resist [Internet]. 2021 [citado 22 Feb 2023]; 4(3):573-95. Disponible en: https://cdrjournal.com/article/view/3993

Farley J, Brady WE, Vathipadiekal V, Lankes HA, Coleman R, Morgan MA, et al. Selumetinib in women with recurrent low-grade serous carcinoma of the ovary or peritoneum: an open-label, single-arm, phase 2 study. Lancet Oncol [Internet]. 2013 [citado 22 Feb 2023]; 14(2):134-40. Disponible en: https://www.sciencedirect.com/science/article/pii/S1470204512705727

Arend RC, Davis AM, Chimiczewski P, O’Malley DM, Provencher D, Vergote I, et al. EMR 20006-012: A phase II randomized double-blind placebo controlled trial comparing the combination of pimasertib (MEK inhibitor) with SAR245409 (PI3K inhibitor) to pimasertib alone in patients with previously treated unresectable borderline or low grade ovarian cancer. Gyn Oncol [Internet]. 2020 [citado 22 Feb 2023]; 156(2):301-7. Disponible en: https://www.sciencedirect.com/science/article/pii/S009082581931786X

Zhang Y, Cao L, Nguyen D, Lu H. TP53 mutations in epithelial ovarian cancer. Transl Cancer Res [Internet]. 2016 [citado 22 Feb 2023]; 5(6):650-63. DOI: http://dx.doi.org/10.21037/tcr.2016.08.40

Ray-Coquard I, Braicu I, Berger R, Mahner S, Sehouli J, Pujade-Lauraine E, et al. Part I of GANNET53: A European multicenter phase I/II trial of the Hsp90 inhibitor ganetespib combined with weekly paclitaxel in women with high-grade, platinum-resistant epithelial ovarian cancer-A study of the GANNET53 consortium. Front Oncol [Internet]. 2019 [citado 22 Feb 2023]; 9:832. DOI: http://dx.doi.org/10.3389/fonc.2019.00832

Fan CA, Reader J, Roque DM. Review of immune therapies targeting ovarian cancer. Curr Treat Options Oncol [Internet]. 2018 [citado 22 Feb 2023]; 19(12):74. DOI: http://dx.doi.org/10.1007/s11864-018-0584-3

Maiorano BA, Maiorano MFP, Lorusso D, Maiello E. Ovarian cancer in the era of immune checkpoint inhibitors: State of the art and future perspectives. Cancers (Basel) [Internet]. 2021 [citado 22 Feb 2023]; 13(17):4438. Disponible en: https://www.mdpi.com/2072-6694/13/17/4438/htm

Matulonis UA, Shapira-Frommer R, Santin AD, Lisyanskaya AS, Pignata S, Vergote I, et al. Antitumor activity and safety of pembrolizumab in patients with advanced recurrent ovarian cancer: results from the phase II KEYNOTE-100 study. Ann Oncol [Internet]. 2019 [citado 22 Feb 2023]; 30(7):1080-7. Disponible en: https://www.sciencedirect.com/science/article/pii/S0923753419312414

Zamarin D, Burger RA, Sill MW, Powell DJ Jr, Lankes HA, Feldman MD, et al. Randomized phase II trial of nivolumab versus nivolumab and ipilimumab for recurrent or persistent ovarian cancer: An NRG oncology study. J Clin Oncol [Internet]. 2020 [citado 22 Feb 2023]; 38(16):1814-23. DOI: http://dx.doi.org/10.1200/JCO.19.02059

Roane BM, Arend RC, Birrer MJ. Review: Targeting the transforming Growth Factor-beta pathway in ovarian cancer. Cancers (Basel) [Internet]. 2019 [citado 22 Feb 2023]; 11(5):668. Disponible en: https://www.mdpi.com/2072-6694/11/5/668/htm

Binju M, Amaya-Padilla MA, Wan G, Gunosewoyo H, Suryo Rahmanto Y, Yu Y. Therapeutic inducers of apoptosis in ovarian cancer. Cancers (Basel) [Internet]. 2019 [citado 22 Feb 2023]; 11(11):1786. Disponible en: https://www.mdpi.com/2072-6694/11/11/1786/htm

Joly F, Fabbro M, Follana P, Lequesne J, Medioni J, Lesoin A, et al. A phase II study of Navitoclax (ABT-263) as single agent in women heavily pretreated for recurrent epithelial ovarian cancer: The MONAVI - GINECO study. Gyn Oncol [Internet]. 2022 [citado 22 Feb 2023]; 165(1):30-9. Disponible en: https://www.sciencedirect.com/science/article/pii/S0090825822000488

Singh T, Neal A, Dibernardo G, Raheseparian N, Moatamed NA, Memarzadeh S. Efficacy of birinapant in combination with carboplatin in targeting platinum resistant epithelial ovarian cancers. Int J Oncol [Internet]. 2022 [citado 22 Feb 2023]; 60(3):1-11. Disponible en: https://www.spandidos-publications.com/ijo/60/3/35

Thibault B, Genre L, Le Naour A, Broca C, Mery E, Vuagniaux G, et al. DEBIO 1143, an IAP inhibitor, reverses carboplatin resistance in ovarian cancer cells and triggers apoptotic or necroptotic cell death. Sci Rep [Internet]. 2018 [citado 22 Feb 2023]; 8(1):17862. Disponible en: https://www.nature.com/articles/s41598-018-35860-z

Zsiros E, Lynam S, Attwood KM, Wang C, Chilakapati S, Gomez EC, et al. Efficacy and safety of pembrolizumab in combination with bevacizumab and oral metronomic cyclophosphamide in the treatment of recurrent ovarian cancer: A phase 2 nonrandomized clinical trial: A phase 2 nonrandomized clinical trial. JAMA Oncol [Internet]. 2021 [citado 22 Feb 2023]; 7(1):78-85. Disponible en: https://pubmed.ncbi.nlm.nih.gov/33211063/

Colombo N, Tomao F, Benedetti Panici P, Nicoletto MO, Tognon G, Bologna A, et al. Randomized phase II trial of weekly paclitaxel vs. cediranib-olaparib (continuous or intermittent schedule) in platinum-resistant high-grade epithelial ovarian cancer. Gyn Oncol [Internet]. 2022 [citado 22 Feb 2023]; 164(3):505-13. Disponible en: https://www.sciencedirect.com/science/article/pii/S0090825822000233

Wang H, Ren B, Liu Y, Jiang B, Guo Y, Wei M, et al. Discovery of pamiparib (BGB-290), a potent and selective poly (ADP-ribose) polymerase (PARP) inhibitor in clinical development. J Med Chem [Internet]. 2020 [citado 29 Abr 023]; 63(24):15541–63. DOI: http://dx.doi.org/10.1021/acs.jmedchem.0c01346

Sun X, Chen W, Qu X, Chen Y. Case Report: Fluzoparib for multiple lines of chemotherapy refractory in metastatic cutaneous squamous cell carcinoma with BRCA2 pathogenic mutation. Front Pharmacol [Internet]. 2022 [citado 29 Abr 2023]; 13:968060. DOI: http://dx.doi.org/10.3389/fphar.2022.968060

Miguel KL, Ávila DRM, Pérez LÁ, Rabasa GM, Lambert AL, Noa RE, et al. The administration of ocoxin increases the quality of life of patients with advanced epithelial or metastatic ovarian cancer undergoing neoadjuvant chemotherapy. J Cancer Ther [Internet]. 2022 [citado 6 Mayo 2023]; 13(09):561-84. Disponible en: https://www.scirp.org/journal/paperinformation.aspx?paperid=119757

Ramírez JS, Díaz YM, Romero MB, Bernal FH, Ávila MA, Gavilondo Cowley JV, et al. Novel contributions to the study of immunological effectors induced by the specific active immunotherapy CIGB-247. Biotecnol Apl [Internet]. 2022 [citado 6 Mayo 2023]; 39(1):1501-7. Disponible en: https://www.medigraphic.com/cgi-bin/new/resumenI.cgi?IDARTICULO=106746

Registro Público Cubano de Ensayos Clínicos. Racotumomab-alumina en cancer de ovario recurrente platino sensible [Internet]. La Habana: RPCEC; 2007 Jul [citado 6 Mayo 2023]. Disponible en: https://rpcec.sld.cu/ensayos/RPCEC00000199-Sp

Hassin O, Oren M. Drugging p53 in cancer: one protein, many targets. Nat Rev Drug Discov [Internet]. 2023 [citado 6 Mayo 2023]; 22(2):127-44. Disponible en: https://www.nature.com/articles/s41573-022-00571-8

DOI: http://dx.doi.org/10.5281/zenodo.8148408



Copyright (c) 2023 Carmita Lemus-Valdés, Alejandro Padrón-Albertus

Licencia de Creative Commons
Esta obra está bajo una licencia de Creative Commons Reconocimiento 4.0 Internacional.