Abstract
Ovarian cancer (OC) is the second most common gynaecological malignancy. It typically affects females over the age of 50, and since 75% of cases are only discovered at stage III or IV, this is a sign of a poor diagnosis. Despite intraperitoneal chemotherapy's chemosensitivity, most patients relapse and face death. Early detection is difficult, but treatment is also difficult due to the route of administration, resistance to therapy with recurrence, and the need for precise cancer targeting to minimize cytotoxicity and adverse effects.
On the other hand, undergoing debulking surgery becomes challenging, and therapy with many chemotherapeutic medications has manifested resistance, a condition known as multidrug resistance (MDR). Although there are other therapeutic options for ovarian cancer, this article solely focuses on co-delivery techniques, which work via diverse pathways to overcome cancer cell resistance. Different pathways contribute to MDR development in ovarian cancer; however, usually, pump and non-pump mechanisms are involved. Striking cancerous cells from several angles is important to defeat MDR. Nanocarriers are known to bypass the drug efflux pump found on cellular membranes to hit the pump mechanism.
Nanocarriers aid in the treatment of ovarian cancer by enhancing the delivery of chemotherapeutic drugs to the tumour sites through passive or active targeting, thereby reducing unfavorable side effects on the healthy tissues. Additionally, the enhanced permeability and retention (EPR) mechanism boosts the bioavailability of the tumour site. To address the shortcomings of conventional delivery, the current review attempts to explain the current conventional treatment with special reference to passively and actively targeted drug delivery systems (DDSs) towards specific receptors developed to treat ovarian cancer. In conclusion, tailored nanocarriers would optimize medication delivery into the intracellular compartment before optimizing intra-tumour distribution. Other novel treatment possibilities for ovarian cancer include tumour vaccines, gene therapy, targeting epigenetic alteration, and biologically targeted compounds. These characteristics might enhance the therapeutic efficacy.
Keywords: Ovaries, ovarian cancer, multidrug resistance, chemotherapy, nanocarriers, nano-systems.
[http://dx.doi.org/10.1016/j.bpobgyn.2005.10.007] [PMID: 16359925]
[http://dx.doi.org/10.1016/S1535-6108(04)00002-9] [PMID: 14749123]
[http://dx.doi.org/10.3390/cancers11030416] [PMID: 30909618]
[http://dx.doi.org/10.3390/ijms20061466] [PMID: 30909510]
[http://dx.doi.org/10.1093/annonc/mdj978] [PMID: 16807453]
[http://dx.doi.org/10.1056/NEJMoa0908806] [PMID: 20818904]
[http://dx.doi.org/10.3390/jcm8030380] [PMID: 30889935]
[http://dx.doi.org/10.1016/S0140-6736(09)61338-6] [PMID: 19793610]
[http://dx.doi.org/10.1007/BF02976620] [PMID: 12135091]
[http://dx.doi.org/10.1097/CAD.0b013e3280113338] [PMID: 17159596]
[http://dx.doi.org/10.1016/S0378-5173(98)00188-4] [PMID: 15129967]
[http://dx.doi.org/10.3390/medicina55060294] [PMID: 31226865]
[http://dx.doi.org/10.3390/ijerph16122185] [PMID: 31226768]
[http://dx.doi.org/10.3390/ma12121991] [PMID: 31234290]
[http://dx.doi.org/10.1016/j.ygyno.2012.07.106] [PMID: 22835718]
[PMID: 11294827]
[http://dx.doi.org/10.1007/978-1-4757-1942-0_15]
[http://dx.doi.org/10.1111/j.1471-0528.1989.tb03341.x] [PMID: 2775686]
[http://dx.doi.org/10.1080/21691401.2019.1677680] [PMID: 31625408]
[http://dx.doi.org/10.1016/0002-9378(86)90623-X] [PMID: 3953714]
[http://dx.doi.org/10.1111/j.1471-0528.1998.tb10148.x] [PMID: 9637117]
[http://dx.doi.org/10.1148/rg.313105066] [PMID: 21571648]
[http://dx.doi.org/10.1158/1055-9965.98.14.1] [PMID: 15668482]
[http://dx.doi.org/10.1038/modpathol.3800306] [PMID: 15761464]
[http://dx.doi.org/10.1097/PGP.0b013e318161e4f5]
[http://dx.doi.org/10.1111/j.1471-0528.1999.tb08137.x] [PMID: 10549956]
[http://dx.doi.org/10.1080/20022727.2017.1335567] [PMID: 30410707]
[http://dx.doi.org/10.1016/j.jconrel.2011.06.001] [PMID: 21663778]
[http://dx.doi.org/10.2174/1568009616666151113120705] [PMID: 26563882]
[http://dx.doi.org/10.1038/nrc2789] [PMID: 20075923]
[http://dx.doi.org/10.1016/j.addr.2013.07.012] [PMID: 23880506]
[http://dx.doi.org/10.1016/j.ctrv.2008.04.003] [PMID: 18538481]
[PMID: 25071577]
[http://dx.doi.org/10.1016/j.addr.2013.09.019] [PMID: 24120656]
[http://dx.doi.org/10.3181/0808-MR-250] [PMID: 19064945]
[http://dx.doi.org/10.3390/gels4030062] [PMID: 30674838]
[http://dx.doi.org/10.3390/jfb9010013] [PMID: 29364833]
[http://dx.doi.org/10.1155/2016/1087250] [PMID: 27398083]
[http://dx.doi.org/10.1021/acsami.5b11103] [PMID: 26771508]
[http://dx.doi.org/10.4155/tde-2017-0062] [PMID: 29061101]
[http://dx.doi.org/10.1021/acs.biomac.6b01885] [PMID: 28245646]
[http://dx.doi.org/10.1038/srep14813] [PMID: 26437582]
[http://dx.doi.org/10.2147/IJN.S137574] [PMID: 28652731]
[http://dx.doi.org/10.1016/j.jclepro.2018.10.182]
[http://dx.doi.org/10.1016/j.surfin.2019.01.008]
[http://dx.doi.org/10.1016/j.jallcom.2020.155118]
[http://dx.doi.org/10.1039/C6MD00293E]
[http://dx.doi.org/10.1016/j.actbio.2019.11.027] [PMID: 31759124]
[http://dx.doi.org/10.7150/thno.29232] [PMID: 31244934]
[http://dx.doi.org/10.2217/nnm-2017-0036] [PMID: 28573926]
[http://dx.doi.org/10.1016/j.eurpolymj.2018.09.011]
[http://dx.doi.org/10.1002/advs.201600134] [PMID: 27980988]
[http://dx.doi.org/10.1016/j.msec.2020.111196] [PMID: 32806317]
[http://dx.doi.org/10.3390/pharmaceutics12050439] [PMID: 32397428]
[http://dx.doi.org/10.1007/s11051-019-4735-7]
[http://dx.doi.org/10.1007/s10967-020-07058-z]
[http://dx.doi.org/10.1038/s41598-017-11533-1] [PMID: 28935923]
[http://dx.doi.org/10.2147/IJN.S122859] [PMID: 28280323]
[http://dx.doi.org/10.1016/j.lfs.2020.118914] [PMID: 33340527]
[http://dx.doi.org/10.1016/j.biomaterials.2012.06.011] [PMID: 22749449]
[http://dx.doi.org/10.1016/j.tips.2009.08.004] [PMID: 19837467]
[http://dx.doi.org/10.3892/mmr.2018.8811] [PMID: 29620264]
[http://dx.doi.org/10.1016/j.ijpharm.2009.12.061] [PMID: 20060458]
[http://dx.doi.org/10.1016/j.jconrel.2013.10.025] [PMID: 24459693]
[http://dx.doi.org/10.1016/j.canlet.2003.12.028] [PMID: 15327831]
[http://dx.doi.org/10.3390/cancers12010213] [PMID: 31952210]
[http://dx.doi.org/10.1080/03639045.2017.1405973] [PMID: 29188736]
[http://dx.doi.org/10.1002/med.21506] [PMID: 29846948]
[http://dx.doi.org/10.1371/journal.pone.0100732] [PMID: 24964012]
[http://dx.doi.org/10.1007/s11095-020-2759-4] [PMID: 32166361]
[http://dx.doi.org/10.1080/00914037.2020.1776282]
[http://dx.doi.org/10.1039/C9BM01662G] [PMID: 31840696]
[http://dx.doi.org/10.1016/j.jinorgbio.2011.05.017] [PMID: 21704583]
[http://dx.doi.org/10.1016/j.drudis.2016.09.013] [PMID: 27671487]
[http://dx.doi.org/10.3390/biom9080330] [PMID: 31374911]
[http://dx.doi.org/10.1016/j.biomaterials.2014.10.044] [PMID: 25453973]
[http://dx.doi.org/10.3390/antiox9020133] [PMID: 32028640]
[http://dx.doi.org/10.1016/j.ygyno.2006.02.029] [PMID: 16626792]
[http://dx.doi.org/10.1016/j.ijpharm.2004.08.008] [PMID: 15501011]
[http://dx.doi.org/10.1124/jpet.108.140095] [PMID: 18780831]
[http://dx.doi.org/10.3109/10717541003762854] [PMID: 20429844]
[http://dx.doi.org/10.1016/j.addr.2009.04.010] [PMID: 19422870]
[http://dx.doi.org/10.1245/s10434-008-0048-2] [PMID: 18636295]
[http://dx.doi.org/10.1093/neuonc/5.2.79] [PMID: 12672279]
[http://dx.doi.org/10.1016/S0168-3659(02)00008-1] [PMID: 11943384]
[http://dx.doi.org/10.1016/j.jconrel.2009.01.007] [PMID: 19331864]
[http://dx.doi.org/10.1002/jps.20379] [PMID: 15920770]
[http://dx.doi.org/10.1016/j.jconrel.2005.02.008] [PMID: 15866344]
[http://dx.doi.org/10.1007/s00280-007-0449-0] [PMID: 17375303]
[http://dx.doi.org/10.1016/j.addr.2012.09.006] [PMID: 12204596]
[PMID: 23678444]
[http://dx.doi.org/10.2147/IJN.S241428] [PMID: 32210557]
[http://dx.doi.org/10.1016/j.carbon.2020.02.060]
[http://dx.doi.org/10.1097/CAD.0b013e328304355f] [PMID: 18594214]
[http://dx.doi.org/10.1016/j.nano.2011.10.014] [PMID: 23066648]
[http://dx.doi.org/10.1016/j.jphotobiol.2013.11.007] [PMID: 24333764]
[http://dx.doi.org/10.1016/j.jconrel.2014.05.042] [PMID: 24878182]
[http://dx.doi.org/10.1177/1533033818791795] [PMID: 30099929]
[http://dx.doi.org/10.1016/j.biomaterials.2007.01.014] [PMID: 17257668]
[http://dx.doi.org/10.3390/cancers11111760] [PMID: 31717427]
[http://dx.doi.org/10.1080/21691401.2019.1576705] [PMID: 30892967]
[http://dx.doi.org/10.1007/s11095-007-9298-0] [PMID: 17447121]
[http://dx.doi.org/10.1016/j.jconrel.2007.09.013] [PMID: 18083265]
[PMID: 10632366]
[http://dx.doi.org/10.1016/j.jconrel.2006.10.007] [PMID: 17113177]
[http://dx.doi.org/10.1016/j.ijpharm.2008.04.031] [PMID: 18550303]
[http://dx.doi.org/10.1016/j.ijpharm.2009.05.003] [PMID: 19442712]
[http://dx.doi.org/10.1016/j.biomaterials.2009.04.003] [PMID: 19394688]
[http://dx.doi.org/10.18433/J3QW26] [PMID: 21501556]
[http://dx.doi.org/10.1158/1535-7163.MCT-10-0249] [PMID: 20530719]
[http://dx.doi.org/10.1016/S0140-6736(10)60893-8] [PMID: 20609468]
[http://dx.doi.org/10.1016/S1470-2045(11)70214-5] [PMID: 21862407]
[http://dx.doi.org/10.1093/annonc/mdw133] [PMID: 26961146]
[http://dx.doi.org/10.1016/S1470-2045(13)70240-7] [PMID: 23810788]
[http://dx.doi.org/10.1016/j.ygyno.2015.03.042] [PMID: 25818403]
[http://dx.doi.org/10.1200/jco.2015.33.15_suppl.5508]
[http://dx.doi.org/10.1016/j.cell.2012.02.015] [PMID: 22424221]
[http://dx.doi.org/10.1016/j.cell.2011.02.013] [PMID: 21376230]
[http://dx.doi.org/10.1200/JCO.2011.37.6418] [PMID: 23509311]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-0521] [PMID: 25125258]
[http://dx.doi.org/10.1093/annonc/mdw084] [PMID: 27141063]
[http://dx.doi.org/10.1016/j.ijpharm.2015.01.009] [PMID: 25578367]
[http://dx.doi.org/10.3109/10717544.2014.923068] [PMID: 24901206]
[http://dx.doi.org/10.2147/IJN.S362263] [PMID: 35836838]
[http://dx.doi.org/10.3390/pharmaceutics14071483] [PMID: 35890378]
[http://dx.doi.org/10.1038/nrd2656] [PMID: 19043449]
[http://dx.doi.org/10.1038/nrclinonc.2010.174] [PMID: 20975744]
[http://dx.doi.org/10.1038/nature14418] [PMID: 25901683]
[http://dx.doi.org/10.1016/S1470-2045(14)71135-0] [PMID: 25481791]
[http://dx.doi.org/10.1016/j.ygyno.2014.02.039] [PMID: 24607283]
[http://dx.doi.org/10.1200/JCO.2014.58.8848] [PMID: 25779564]
[http://dx.doi.org/10.1016/S1470-2045(14)70228-1] [PMID: 24882434]
[http://dx.doi.org/10.1200/JCO.2014.56.2728] [PMID: 25366685]
[http://dx.doi.org/10.1200/JCO.2015.62.3397] [PMID: 26351349]
[http://dx.doi.org/10.1200/JCO.2007.12.0782] [PMID: 18024865]
[http://dx.doi.org/10.1016/j.critrevonc.2015.05.009] [PMID: 26126494]
[http://dx.doi.org/10.1517/14728214.2015.1036739] [PMID: 26001052]
[http://dx.doi.org/10.1200/JCO.2009.23.2777] [PMID: 19826113]
[http://dx.doi.org/10.1073/pnas.0712237105] [PMID: 18287062]
[http://dx.doi.org/10.1016/j.annonc.2020.06.004] [PMID: 32569725]
[http://dx.doi.org/10.1080/14712598.2020.1776253] [PMID: 32463296]
[http://dx.doi.org/10.4161/hv.20738] [PMID: 22906947]
[http://dx.doi.org/10.3390/diagnostics9030087] [PMID: 31374917]
[PMID: 347606]
[http://dx.doi.org/10.1200/jco.2011.29.15_suppl.5011]
[http://dx.doi.org/10.1038/bjc.2014.116] [PMID: 24642620]
[http://dx.doi.org/10.1002/cncr.25701] [PMID: 21472713]
[http://dx.doi.org/10.1007/s10637-013-0003-3] [PMID: 23907406]
[http://dx.doi.org/10.1016/j.ygyno.2013.11.008] [PMID: 24239753]
[http://dx.doi.org/10.1002/cncr.29082] [PMID: 25336142]
[http://dx.doi.org/10.1016/j.ygyno.2014.08.004] [PMID: 25124162]
[http://dx.doi.org/10.1200/JCO.2015.63.6480] [PMID: 27069082]
[http://dx.doi.org/10.1007/s11095-010-0214-7] [PMID: 20814720]
[http://dx.doi.org/10.1038/nrc1369] [PMID: 15170445]
[http://dx.doi.org/10.1038/nrclinonc.2009.217] [PMID: 20010898]
[http://dx.doi.org/10.1152/ajprenal.00313.2004] [PMID: 15692055]
[http://dx.doi.org/10.1002/jbm.a.30654] [PMID: 16425240]
[http://dx.doi.org/10.1038/nm.2472] [PMID: 21926976]
[http://dx.doi.org/10.3390/ijms19071930] [PMID: 29966369]
[http://dx.doi.org/10.18632/oncotarget.5093] [PMID: 26418751]
[http://dx.doi.org/10.1248/bpb.b12-01102] [PMID: 23649331]
[http://dx.doi.org/10.1016/j.msec.2014.06.002] [PMID: 25491871]
[http://dx.doi.org/10.1016/S0168-3659(03)00209-8] [PMID: 12932638]
[http://dx.doi.org/10.1016/j.ijpharm.2017.09.060] [PMID: 28947245]
[http://dx.doi.org/10.2353/ajpath.2010.100105] [PMID: 20651229]
[http://dx.doi.org/10.1002/14651858.CD005340.pub4] [PMID: 26755441]
[http://dx.doi.org/10.1016/S0025-6196(11)61196-8] [PMID: 17550756]
[PMID: 9713471]
[http://dx.doi.org/10.1517/17425247.2012.665366] [PMID: 22452661]
[http://dx.doi.org/10.1093/annonc/mdx443] [PMID: 29232466]
[http://dx.doi.org/10.1111/j.1471-0528.2004.00157.x] [PMID: 15198792]
[http://dx.doi.org/10.1021/mp500628g] [PMID: 25536192]
[http://dx.doi.org/10.1056/NEJM197604082941506] [PMID: 765825]