Abstract
Ovarian cancer (OC) is one of the most common malignancies in women and is associated with poor outcomes. The treatment for OC is often associated with resistance to therapies and hence this has stimulated the search for alternative therapeutic approaches, including RNA-based therapeutics. However, this approach has some challenges that include RNA degradation. To solve this critical issue, some novel delivery systems have been proposed. In current years, there has been growing interest in the improvement of RNAbased therapeutics as a promising approach to target ovarian cancer and improve patient outcomes. This paper provides a practical insight into the use of RNA-based therapeutics in ovarian cancers, highlighting their potential benefits, challenges, and current research progress. RNA-based therapeutics offer a novel and targeted approach to treat ovarian cancer by exploiting the unique characteristics of RNA molecules. By targeting key oncogenes or genes responsible for drug resistance, siRNAs can effectively inhibit tumor growth and sensitize cancer cells to conventional therapies. Furthermore, messenger RNA (mRNA) vaccines have emerged as a revolutionary tool in cancer immunotherapy. MRNA vaccines can be designed to encode tumor-specific antigens, stimulating the immune system to distinguish and eliminate ovarian cancer cells. A nano-based delivery platform improves the release of loaded RNAs to the target location and reduces the off-target effects. Additionally, off-target effects and immune responses triggered by RNA molecules necessitate careful design and optimization of these therapeutics. Several preclinical and clinical researches have shown promising results in the field of RNA-based therapeutics for ovarian cancer. In a preclinical study, siRNA-mediated silencing of the poly (ADP-ribose) polymerase 1 (PARP1) gene, involved in DNA repair, sensitized ovarian cancer cells to PARP inhibitors, leading to enhanced therapeutic efficacy. In clinical trials, mRNA-based vaccines targeting tumor-associated antigens have demonstrated safety and efficacy in stimulating immune responses in ovarian cancer patients. In aggregate, RNA-based therapeutics represent a promising avenue for the therapy of ovarian cancers. The ability to specifically target oncogenes or stimulate immune responses against tumor cells holds great potential for improving patient outcomes. However, further research is needed to address challenges related to delivery, permanence, and off-target effects. Clinical trials assessing the care and effectiveness of RNAbased therapeutics in larger patient cohorts are warranted. With continued advancements in the field, RNAbased therapeutics have the potential to develop the management of ovarian cancer and provide new hope for patients.
Keywords: Ovarian cancer, RNA-based therapeutics, nanocarriers, siRNA, mRNA vaccine, nano-based delivery.
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.1016/j.ejca.2015.07.022] [PMID: 26421822]
[http://dx.doi.org/10.1016/j.biopha.2020.110401] [PMID: 32570116]
[http://dx.doi.org/10.20892/j.issn.2095-3941.2016.0084] [PMID: 28443200]
[http://dx.doi.org/10.1093/annonc/mdz062] [PMID: 31046081]
[http://dx.doi.org/10.3390/ijms18102171] [PMID: 29057791]
[http://dx.doi.org/10.3389/fphar.2013.00028] [PMID: 23504227]
[http://dx.doi.org/10.2174/1567201818666210609161301] [PMID: 34151759]
[http://dx.doi.org/10.1016/j.adcanc.2022.100047]
[http://dx.doi.org/10.1016/j.adcanc.2022.100041]
[http://dx.doi.org/10.3389/fonc.2015.00149] [PMID: 26175968]
[http://dx.doi.org/10.1016/S0002-9440(10)63306-8] [PMID: 15277215]
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.11.028] [PMID: 27890641]
[http://dx.doi.org/10.3390/ijms17122113] [PMID: 27983698]
[http://dx.doi.org/10.1002/ijc.23448] [PMID: 18431743]
[http://dx.doi.org/10.1016/j.canlet.2006.02.018] [PMID: 16584837]
[http://dx.doi.org/10.1371/journal.pone.0047086]
[http://dx.doi.org/10.4161/cbt.4.9.1912] [PMID: 16138005]
[http://dx.doi.org/10.1002/jcp.24069] [PMID: 22331597]
[http://dx.doi.org/10.1016/j.ygyno.2013.05.005] [PMID: 23680521]
[http://dx.doi.org/10.1016/S0169-5002(03)00147-8] [PMID: 12867066]
[http://dx.doi.org/10.1054/bjoc.2001.2139] [PMID: 11742498]
[http://dx.doi.org/10.1158/1078-0432.CCR-05-2433] [PMID: 16609037]
[http://dx.doi.org/10.1046/j.1359-4117.2002.01004.x] [PMID: 12415618]
[http://dx.doi.org/10.1186/1757-2215-6-71] [PMID: 24103397]
[http://dx.doi.org/10.1016/j.biochi.2017.12.001] [PMID: 29224849]
[http://dx.doi.org/10.1016/j.nano.2016.11.015] [PMID: 27890659]
[http://dx.doi.org/10.1016/j.ymeth.2015.10.022] [PMID: 26542762]
[http://dx.doi.org/10.1021/acs.bioconjchem.6b00746] [PMID: 28122449]
[http://dx.doi.org/10.7150/thno.17826] [PMID: 28435472]
[PMID: 12500395]
[http://dx.doi.org/10.1002/ijc.20899] [PMID: 15688364]
[PMID: 14575561]
[http://dx.doi.org/10.1002/mc.10017]
[http://dx.doi.org/10.1159/000485395] [PMID: 29179183]
[http://dx.doi.org/10.18632/oncotarget.8535] [PMID: 27166268]
[http://dx.doi.org/10.2217/fon-2016-0290] [PMID: 27690631]
[http://dx.doi.org/10.18632/oncotarget.5784] [PMID: 26430965]
[http://dx.doi.org/10.1016/j.ccr.2014.07.009] [PMID: 25203321]
[http://dx.doi.org/10.18632/oncotarget.8089] [PMID: 26992233]
[http://dx.doi.org/10.1038/onc.2016.75] [PMID: 27041570]
[http://dx.doi.org/10.1371/journal.pone.0155250] [PMID: 27227769]
[http://dx.doi.org/10.3892/ol.2016.4435] [PMID: 27313681]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-1936] [PMID: 17875710]
[http://dx.doi.org/10.1371/journal.pone.0002436] [PMID: 18560586]
[http://dx.doi.org/10.1172/JCI161981] [PMID: 35968784]
[http://dx.doi.org/10.1016/j.prp.2020.153275] [PMID: 33285422]
[http://dx.doi.org/10.3390/medicina55060294] [PMID: 31226865]
[http://dx.doi.org/10.3389/fphar.2021.644718] [PMID: 33796026]
[http://dx.doi.org/10.1021/jm00059a007] [PMID: 8464037]
[PMID: 11181921]
[http://dx.doi.org/10.1016/j.bbrc.2007.06.177] [PMID: 17658482]
[http://dx.doi.org/10.1038/s12276-020-0407-z] [PMID: 32210357]
[http://dx.doi.org/10.1007/s12033-022-00490-4] [PMID: 35474410]
[http://dx.doi.org/10.3390/ijerph16122185] [PMID: 31226768]
[http://dx.doi.org/10.3390/molecules25051088] [PMID: 32121130]
[http://dx.doi.org/10.7150/thno.21254] [PMID: 29556336]
[http://dx.doi.org/10.1158/1078-0432.CCR-11-0430] [PMID: 21831956]
[http://dx.doi.org/10.3390/jfb9010013] [PMID: 29364833]
[http://dx.doi.org/10.1006/gyno.2002.6708] [PMID: 12586109]
[http://dx.doi.org/10.1016/j.addr.2012.09.006] [PMID: 12204596]
[http://dx.doi.org/10.1038/nrd1088] [PMID: 12750738]
[http://dx.doi.org/10.1002/ijc.22886] [PMID: 17557285]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-4973] [PMID: 18483388]
[http://dx.doi.org/10.1016/j.ctrv.2008.04.003] [PMID: 18538481]
[http://dx.doi.org/10.1016/j.jconrel.2010.01.036] [PMID: 20226220]
[http://dx.doi.org/10.1016/j.drudis.2009.07.010] [PMID: 19647803]
[http://dx.doi.org/10.1002/jps.21479] [PMID: 18623213]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-4721] [PMID: 19638590]
[http://dx.doi.org/10.3390/cancers12010213] [PMID: 31952210]
[http://dx.doi.org/10.1002/adtp.201800065]
[http://dx.doi.org/10.1038/mt.2009.36] [PMID: 19259063]
[http://dx.doi.org/10.1080/20013078.2017.1422676] [PMID: 29372017]
[http://dx.doi.org/10.1038/ncb1596] [PMID: 17486113]
[http://dx.doi.org/10.1155/2015/701390]
[http://dx.doi.org/10.1111/j.1582-4934.2011.01316.x] [PMID: 21435174]
[http://dx.doi.org/10.1007/s10495-010-0534-4] [PMID: 20717727]
[PMID: 24747178]
[PMID: 22619510]
[http://dx.doi.org/10.1155/2019/2595801]
[http://dx.doi.org/10.1016/j.actbio.2019.12.015] [PMID: 31846802]
[http://dx.doi.org/10.1016/j.ygyno.2004.03.023] [PMID: 15196867]
[http://dx.doi.org/10.1016/j.mtcomm.2021.102064]
[http://dx.doi.org/10.1016/j.jddst.2022.103603]
[http://dx.doi.org/10.3389/fbioe.2023.1160985] [PMID: 37082219]
[http://dx.doi.org/10.1016/j.biotechadv.2019.107502] [PMID: 31887345]
[http://dx.doi.org/10.1016/j.jconrel.2018.05.012] [PMID: 29777795]
[http://dx.doi.org/10.1016/j.ygyno.2004.07.011] [PMID: 15385103]
[http://dx.doi.org/10.1200/JCO.2006.09.6735] [PMID: 17602086]
[http://dx.doi.org/10.1200/JCO.2007.13.6606] [PMID: 18281662]
[http://dx.doi.org/10.1007/s40265-017-0741-1] [PMID: 28401446]
[http://dx.doi.org/10.1016/j.bioactmat.2021.10.018] [PMID: 35310381]
[http://dx.doi.org/10.1200/JCO.2013.55.0376] [PMID: 25403217]
[http://dx.doi.org/10.1073/pnas.1411393111] [PMID: 25049380]
[http://dx.doi.org/10.1021/jm050044o] [PMID: 15974578]
[http://dx.doi.org/10.2174/156652309790031148] [PMID: 20021329]
[http://dx.doi.org/10.1016/j.ygyno.2006.02.029] [PMID: 16626792]
[http://dx.doi.org/10.1016/S0168-3659(02)00008-1] [PMID: 11943384]
[http://dx.doi.org/10.1517/17425247.2012.665366] [PMID: 22452661]
[http://dx.doi.org/10.1021/mp900093r] [PMID: 19397332]
[http://dx.doi.org/10.1038/nmeth854] [PMID: 16489337]
[http://dx.doi.org/10.1038/nbt831] [PMID: 12754523]
[http://dx.doi.org/10.4103/0019-509X.175598] [PMID: 26837960]
[http://dx.doi.org/10.2174/138920011794520017] [PMID: 21222588]
[http://dx.doi.org/10.1177/2472630318816668] [PMID: 30616494]
[http://dx.doi.org/10.1016/j.bbrc.2006.02.049] [PMID: 16598842]
[http://dx.doi.org/10.1038/nature03121] [PMID: 15538359]
[http://dx.doi.org/10.1038/mt.2008.14]
[http://dx.doi.org/10.1038/nbt1339] [PMID: 17873866]
[http://dx.doi.org/10.1016/j.ijpharm.2010.01.019] [PMID: 20080162]
[http://dx.doi.org/10.1111/j.1349-7006.2010.01650.x] [PMID: 20624164]
[http://dx.doi.org/10.1186/1471-2407-10-10] [PMID: 20064265]
[PMID: 21572539]
[http://dx.doi.org/10.1261/rna.30706] [PMID: 16682562]
[http://dx.doi.org/10.1021/bc700421u] [PMID: 18393455]
[http://dx.doi.org/10.1261/rna.1305209] [PMID: 19228587]