Abstract
Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy. Although initial response rates to standard platinum-based treatment are at 70–80%, long-term response in advanced EOC disease is rarely achieved with the development of chemoresistance and recurrence, contributing to overall survival rates below 45%. Additional challenges stem from EOC heterogeneity, reflecting at least five histological subtypes, each with different underlying molecular characteristics and clinicopathology that have significant implications in treatment effectiveness and management. Since the last decade, technologies in genomics, proteomics and pathology have been deployed to find reliable clinical markers that can identify patients sensitive to standard chemotherapy treatments and stratify patients for more suitable targeted therapies. These efforts have identified several molecular markers of prognostic value that have been validated as biomarkers, such as BRCA and KRAS mutations, or are currently under investigation in clinical trials, such as CD8 T cells, immune checkpoint inhibitors and progesterone receptor. Recent advancements in biomarker research have also revealed new targets that have expanded treatment options, introducing poly (ADP-ribose) polymerase (PARP) inhibitors, anti-angiogenic agents, inhibitors targeting signaling pathways, and immunotherapy to improve maintenance therapies or enhance first-line therapy. This review presents a summary of current biomarkers, in clinical use or under evaluation, demonstrating a potential to inform on patient selection for treatment efficacy and predict response to EOC therapies, with particular focus on the serous subtypes, including high-grade and low-grade serous carcinomas.
Keywords: BRCA, markers, PARP inhibitors, immunotherapy, anti-angiogenic therapy, hormone therapy, long-term survival, targeted therapy, high-grade serous, low-grade serous.
Graphical Abstract
[http://dx.doi.org/10.1038/nrc4019] [PMID: 26493647]
[http://dx.doi.org/10.1038/nrdp.2016.61] [PMID: 27558151]
[http://dx.doi.org/10.1016/S0140-6736(18)32552-2] [PMID: 30910306]
[http://dx.doi.org/10.3390/ijms20040952] [PMID: 30813239]
[http://dx.doi.org/10.3322/caac.21492] [PMID: 30207593]
[http://dx.doi.org/10.20892/j.issn.2095-3941.2016.0084] [PMID: 28443200]
[http://dx.doi.org/10.1016/j.biopha.2018.11.097] [PMID: 30551510]
[http://dx.doi.org/10.1007/s13402-016-0309-1] [PMID: 27981507]
[http://dx.doi.org/10.1111/his.13248] [PMID: 28477361]
[http://dx.doi.org/10.1097/01.pas.0000180854.28831.77] [PMID: 16434898]
[http://dx.doi.org/10.1038/s41467-017-00962-1] [PMID: 29061967]
[http://dx.doi.org/10.1158/1940-6207.CAPR-18-0009] [PMID: 30232083]
[http://dx.doi.org/10.1016/j.bpobgyn.2016.11.004] [PMID: 28027849]
[http://dx.doi.org/10.1080/14737159.2016.1259069] [PMID: 27828713]
[http://dx.doi.org/10.1093/annonc/mds203] [PMID: 22910840]
[PMID: 27993805]
[http://dx.doi.org/10.1038/s41598-017-10432-9] [PMID: 28852190]
[PMID: 23257362]
[http://dx.doi.org/10.1007/s40471-017-0115-y] [PMID: 29226065]
[PMID: 27993794]
[http://dx.doi.org/10.1097/PAS.0000000000000824] [PMID: 28248817]
[http://dx.doi.org/10.1186/s12885-018-4242-8] [PMID: 29587661]
[http://dx.doi.org/10.1016/j.ajpath.2015.11.011] [PMID: 27012190]
[http://dx.doi.org/10.1097/PGP.0000000000000274] [PMID: 26974996]
[http://dx.doi.org/10.1200/JCO.2016.69.7458] [PMID: 27646940]
[http://dx.doi.org/10.3802/jgo.2015.26.4.336] [PMID: 26197773]
[http://dx.doi.org/10.1093/annonc/mdx754] [PMID: 29186319]
[http://dx.doi.org/10.1016/j.jogoh.2019.03.018] [PMID: 30936025]
[http://dx.doi.org/10.1186/s13048-019-0509-1] [PMID: 30995948]
[http://dx.doi.org/10.1016/j.ygyno.2019.02.008] [PMID: 30765149]
[http://dx.doi.org/10.1097/PGP.0000000000000251] [PMID: 26598982]
[http://dx.doi.org/10.1097/IGC.0000000000000586] [PMID: 26588231]
[http://dx.doi.org/10.1089/bio.2012.0044] [PMID: 24845429]
[http://dx.doi.org/10.1186/bcr1670] [PMID: 17466083]
[http://dx.doi.org/10.1158/1055-9965.EPI-18-0182] [PMID: 30018149]
[http://dx.doi.org/10.1002/ijc.32075] [PMID: 30561796]
[http://dx.doi.org/10.1001/jama.2012.20] [PMID: 22274685]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-2497] [PMID: 25398451]
[http://dx.doi.org/10.1001/jama.2014.5985] [PMID: 25849179]
[http://dx.doi.org/10.1016/j.cell.2018.02.052]
[http://dx.doi.org/10.1080/14737159.2017.1326820] [PMID: 28468520]
[http://dx.doi.org/10.1200/JCO.2003.01.223] [PMID: 12743133]
[http://dx.doi.org/10.1093/annonc/mdw253] [PMID: 27358387]
[http://dx.doi.org/10.1177/1010428317691189] [PMID: 28218038]
[http://dx.doi.org/10.1371/journal.pone.0194270] [PMID: 29584739]
[PMID: 30511925]
[http://dx.doi.org/10.1080/14737159.2018.1457436] [PMID: 29569984]
[http://dx.doi.org/10.1007/s13277-015-4031-9] [PMID: 26419591]
[http://dx.doi.org/10.1186/1746-1596-8-11] [PMID: 23343214]
[http://dx.doi.org/10.1016/j.ygyno.2007.11.020] [PMID: 18222534]
[http://dx.doi.org/10.1038/bjc.2014.567] [PMID: 25349970]
[http://dx.doi.org/10.1371/journal.pone.0006292] [PMID: 19617914]
[http://dx.doi.org/10.1016/j.clinbiochem.2013.03.010] [PMID: 23528302]
[http://dx.doi.org/10.1002/cam4.1944] [PMID: 30761774]
[http://dx.doi.org/10.1038/sj.bjc.6601956] [PMID: 15199393]
[http://dx.doi.org/10.1186/s13048-018-0387-y] [PMID: 29433550]
[http://dx.doi.org/10.1007/s10555-014-9539-8] [PMID: 25564455]
[http://dx.doi.org/10.1038/nature10166] [PMID: 21720365]
[http://dx.doi.org/10.1001/jama.2011.1456] [PMID: 21990299]
[http://dx.doi.org/10.1186/s13048-018-0424-x] [PMID: 29925418]
[http://dx.doi.org/10.3390/cancers11010119] [PMID: 30669514]
[http://dx.doi.org/10.1158/0008-5472.CAN-12-0324] [PMID: 23066035]
[http://dx.doi.org/10.1158/2159-8290.CD-15-0714] [PMID: 26463832]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-2287] [PMID: 24240112]
[http://dx.doi.org/10.3389/fonc.2018.00016] [PMID: 29459887]
[http://dx.doi.org/10.18632/oncotarget.12306] [PMID: 27690218]
[http://dx.doi.org/10.1007/s40259-019-00347-4] [PMID: 30895466]
[http://dx.doi.org/10.18632/oncotarget.24728] [PMID: 29731958]
[http://dx.doi.org/10.18632/oncotarget.6834] [PMID: 26745875]
[http://dx.doi.org/10.1038/nrc.2015.21] [PMID: 26775620]
[PMID: 30133561]
[http://dx.doi.org/10.3389/fonc.2014.00034] [PMID: 24624361]
[http://dx.doi.org/10.1200/JCO.2010.34.2980] [PMID: 21709188]
[http://dx.doi.org/10.1038/nature14410] [PMID: 26017449]
[http://dx.doi.org/10.1093/annonc/mdx446]
[http://dx.doi.org/10.3390/cancers11030416] [PMID: 30909618]
[http://dx.doi.org/10.1016/j.ejca.2017.08.029] [PMID: 28950147]
[http://dx.doi.org/10.1038/bjc.2012.451] [PMID: 23047548]
[PMID: 29858219]
[http://dx.doi.org/10.1056/NEJMoa1611310] [PMID: 27717299]
[http://dx.doi.org/10.1158/1078-0432.CCR-15-2477] [PMID: 26957554]
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0034] [PMID: 29724815]
[http://dx.doi.org/10.1016/j.ygyno.2019.01.015] [PMID: 30686551]
[http://dx.doi.org/10.1080/15384047.2015.1040960] [PMID: 25894333]
[http://dx.doi.org/10.3390/cancers10090302] [PMID: 30200478]
[http://dx.doi.org/10.1158/1078-0432.CCR-18-1481] [PMID: 30049748]
[http://dx.doi.org/10.1186/1479-5876-10-205] [PMID: 23034130]
[http://dx.doi.org/10.1097/IGC.0000000000000672] [PMID: 26905331]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-3862] [PMID: 29661778]
[http://dx.doi.org/10.1016/j.ygyno.2017.05.003] [PMID: 28552394]
[http://dx.doi.org/10.3390/cancers10080242] [PMID: 30042343]
[http://dx.doi.org/10.1001/jamaoncol.2017.3290] [PMID: 29049607]
[http://dx.doi.org/10.1080/2162402X.2018.1424672] [PMID: 29721385]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-1433] [PMID: 27601594]
[http://dx.doi.org/10.1016/j.ygyno.2016.03.008] [PMID: 26972336]
[http://dx.doi.org/10.1158/2326-6066.CIR-14-0239] [PMID: 25957117]
[http://dx.doi.org/10.1002/cjp2.55] [PMID: 27917296]
[http://dx.doi.org/10.1016/j.cell.2018.03.073]
[http://dx.doi.org/10.1016/j.cell.2016.04.009] [PMID: 27133165]
[http://dx.doi.org/10.18632/oncotarget.7277] [PMID: 26871470]
[http://dx.doi.org/10.1530/ERC-12-0175] [PMID: 23045324]
[http://dx.doi.org/10.1200/JCO.2015.66.3245] [PMID: 27001577]
[http://dx.doi.org/10.1016/S1470-2045(13)70253-5] [PMID: 23845225]
[http://dx.doi.org/10.1111/his.13784] [PMID: 30403298]
[http://dx.doi.org/10.1586/14737159.4.2.157] [PMID: 14995903]
[http://dx.doi.org/10.1016/j.ygyno.2016.01.026] [PMID: 26827964]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-6595] [PMID: 18593951]
[PMID: 19967725]
[http://dx.doi.org/10.1038/sj.onc.1208298] [PMID: 15558012]
[http://dx.doi.org/10.1002/emmm.201201823] [PMID: 23666744]
[http://dx.doi.org/10.1093/biolre/ioz099] [PMID: 31187121]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-0196] [PMID: 18698038]
[http://dx.doi.org/10.1158/1055-9965.EPI-13-0192] [PMID: 23917454]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0246] [PMID: 28280090]
[http://dx.doi.org/10.1093/jnci/dju249] [PMID: 25269487]
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0784] [PMID: 30084834]
[http://dx.doi.org/10.1002/path.4536] [PMID: 25810134]
[http://dx.doi.org/10.1016/S1470-2045(16)30559-9] [PMID: 27908594]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0564] [PMID: 27702817]
[http://dx.doi.org/10.1158/2159-8290.CD-14-0358] [PMID: 25168287]
[http://dx.doi.org/10.3389/fonc.2015.00240] [PMID: 26579492]
[http://dx.doi.org/10.1593/neo.111032] [PMID: 22131882]
[http://dx.doi.org/10.1097/MD.0000000000012996] [PMID: 30407287]
[http://dx.doi.org/10.1159/000447337] [PMID: 27487108]
[http://dx.doi.org/10.1038/s41392-018-0034-5] [PMID: 30652029]
[http://dx.doi.org/10.4238/2015.June.29.17] [PMID: 26125934]
[http://dx.doi.org/10.1007/s00280-008-0783-x] [PMID: 18575867]
[http://dx.doi.org/10.1016/j.dnarep.2015.04.002] [PMID: 25956741]
[http://dx.doi.org/10.1016/j.ejca.2010.11.029] [PMID: 21216588]
[http://dx.doi.org/10.1089/dna.2015.2805] [PMID: 25941922]
[http://dx.doi.org/10.1038/tpj.2011.50] [PMID: 22158331]
[http://dx.doi.org/10.1016/j.tjog.2016.02.011] [PMID: 27125404]
[http://dx.doi.org/10.18632/oncotarget.20482] [PMID: 29156754]
[http://dx.doi.org/10.1016/j.ygyno.2019.02.014] [PMID: 30797591]
[http://dx.doi.org/10.1016/j.ygyno.2018.08.030] [PMID: 30194007]
[http://dx.doi.org/10.1186/s13048-018-0414-z] [PMID: 29843813]
[http://dx.doi.org/10.1186/s13048-019-0512-6] [PMID: 31039792]
[http://dx.doi.org/10.1172/JCI96113] [PMID: 29337305]
[http://dx.doi.org/10.1080/2162402X.2019.1596004] [PMID: 31143517]
[http://dx.doi.org/10.1371/journal.pone.0038541] [PMID: 22685580]
[http://dx.doi.org/10.7785/tcrt.2012.500312] [PMID: 23289476]
[http://dx.doi.org/10.1111/imr.12528] [PMID: 28258700]
[http://dx.doi.org/10.3390/cancers10100366] [PMID: 30274280]
[PMID: 30453041]
[http://dx.doi.org/10.1016/j.ejca.2012.06.026] [PMID: 22897840]
[http://dx.doi.org/10.1038/onc.2014.136] [PMID: 24858042]
[http://dx.doi.org/10.18632/oncotarget.13286] [PMID: 28388557]
[http://dx.doi.org/10.1016/j.tranon.2018.07.010] [PMID: 30056367]
[http://dx.doi.org/10.1007/s00018-008-8281-1] [PMID: 18726070]
[http://dx.doi.org/10.1002/ijc.29982] [PMID: 26704932]
[http://dx.doi.org/10.1371/journal.pone.0184439] [PMID: 28934230]
[http://dx.doi.org/10.3390/ijms18061207] [PMID: 28587302]
[PMID: 30373860]
[http://dx.doi.org/10.1080/23723556.2015.1074336] [PMID: 27308596]
[http://dx.doi.org/10.1155/2015/413076] [PMID: 26137480]
[http://dx.doi.org/10.1002/jcp.26289] [PMID: 29152737]
[PMID: 29456815]
[http://dx.doi.org/10.1016/j.bbrc.2016.07.035] [PMID: 27422607]
[http://dx.doi.org/10.1038/bjc.2016.203] [PMID: 27415012]
[http://dx.doi.org/10.1016/j.ygyno.2013.07.107] [PMID: 23917080]
[http://dx.doi.org/10.1371/journal.pone.0040717] [PMID: 22792399]
[http://dx.doi.org/10.1001/jamaoncol.2017.4218] [PMID: 29242937]
[http://dx.doi.org/10.1056/NEJMoa1810858] [PMID: 30345884]
[http://dx.doi.org/10.1038/nrclinonc.2017.161] [PMID: 28994419]
[http://dx.doi.org/10.1200/JCO.18.02238] [PMID: 31173551]
[http://dx.doi.org/10.1158/2159-8290.CD-18-0715] [PMID: 30425037]
[http://dx.doi.org/10.1016/j.clbc.2017.12.010] [PMID: 29325860]
[http://dx.doi.org/10.1158/2159-8290.CD-17-0734] [PMID: 28864639]
[http://dx.doi.org/10.1016/j.dnarep.2018.08.021] [PMID: 30177437]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-0247] [PMID: 27678458]
[http://dx.doi.org/10.1016/j.molcel.2018.12.008]
[http://dx.doi.org/10.1515/BC.2003.167] [PMID: 14669994]
[http://dx.doi.org/10.1016/j.bbrc.2015.05.083] [PMID: 26047697]
[http://dx.doi.org/10.1200/EDBK_160766] [PMID: 27249758]
[http://dx.doi.org/10.1200/EDBK_237967] [PMID: 31099679]
[http://dx.doi.org/10.1038/s41416-019-0384-y] [PMID: 30718808]
[http://dx.doi.org/10.1007/s11864-018-0584-3] [PMID: 30430276]
[http://dx.doi.org/10.1016/j.intimp.2018.06.001] [PMID: 29990692]
[http://dx.doi.org/10.1093/annonc/mdz135] [PMID: 31046082]
[http://dx.doi.org/10.1001/jamaoncol.2018.6258] [PMID: 30676622]
[http://dx.doi.org/10.1038/nm.4333] [PMID: 28481359]
[http://dx.doi.org/10.18632/oncotarget.24770] [PMID: 29707124]
[http://dx.doi.org/10.1084/jem.20140559] [PMID: 25601652]
[http://dx.doi.org/10.3390/biomedicines5020034] [PMID: 28635679]
[http://dx.doi.org/10.1016/j.ygyno.2017.01.027] [PMID: 28139261]
[http://dx.doi.org/10.1016/j.ejca.2017.01.026] [PMID: 28242502]
[http://dx.doi.org/10.1200/JCO.2013.51.4489] [PMID: 24637997]
[http://dx.doi.org/10.1016/S1470-2045(15)00086-8] [PMID: 26115797]
[http://dx.doi.org/10.1016/j.ygyno.2018.08.036] [PMID: 30449719]
[http://dx.doi.org/10.1016/j.ygyno.2018.10.031] [PMID: 30409490]
[http://dx.doi.org/10.1093/jnci/djx066] [PMID: 29059426]
[http://dx.doi.org/10.1016/j.ygyno.2010.08.016] [PMID: 20870280]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-0489] [PMID: 23935036]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3269] [PMID: 24536077]
[http://dx.doi.org/10.1158/1078-0432.CCR-13-3248] [PMID: 24947924]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2196] [PMID: 28159814]
[http://dx.doi.org/10.3390/jcm8030380] [PMID: 30889935]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0647] [PMID: 28855350]
[http://dx.doi.org/10.18632/oncotarget.20410] [PMID: 29228548]
[http://dx.doi.org/10.1016/j.molonc.2011.11.010] [PMID: 22265591]
[http://dx.doi.org/10.1002/ijc.29937] [PMID: 26595060]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-2499] [PMID: 29545464]
[http://dx.doi.org/10.1093/annonc/mdv250] [PMID: 26063635]
[http://dx.doi.org/10.1158/0008-5472.CAN-07-0033] [PMID: 17483358]
[http://dx.doi.org/10.1200/JCO.2013.49.7685] [PMID: 24127448]
[http://dx.doi.org/10.1093/annonc/mdu024] [PMID: 24667717]
[http://dx.doi.org/10.1158/1535-7163.MCT-15-0950] [PMID: 27256377]
[http://dx.doi.org/10.1200/JCO.2016.71.0632] [PMID: 28221866]
[http://dx.doi.org/10.1016/j.ygyno.2017.10.036] [PMID: 29157627]
[http://dx.doi.org/10.1016/j.ygyno.2019.06.011] [PMID: 31227223]
[http://dx.doi.org/10.1016/j.ygyno.2018.11.030] [PMID: 30501904]
[http://dx.doi.org/10.1002/gcc.20883] [PMID: 21563232]
[http://dx.doi.org/10.1158/1535-7163.MCT-11-0996] [PMID: 22556379]
[http://dx.doi.org/10.5732/cjc.014.10289] [PMID: 25556614]
[http://dx.doi.org/10.1055/s-0043-118907] [PMID: 29093603]
[http://dx.doi.org/10.18632/oncotarget.7549] [PMID: 26909613]
[PMID: 27993796]
[http://dx.doi.org/10.3892/ol.2017.6081] [PMID: 28588728]
[http://dx.doi.org/10.1158/1535-7163.MCT-13-0764] [PMID: 24795222]
[http://dx.doi.org/10.1088/1478-3975/ab157a] [PMID: 30939460]
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2727] [PMID: 29273632]
[http://dx.doi.org/10.2353/ajpath.2010.100212] [PMID: 20802181]
[http://dx.doi.org/10.1016/S1470-2045(12)70572-7] [PMID: 23261356]
[http://dx.doi.org/10.1158/1078-0432.CCR-18-0494] [PMID: 29844129]
[http://dx.doi.org/10.1186/s40661-016-0026-5] [PMID: 27231576]
[http://dx.doi.org/10.1016/j.gore.2019.01.007] [PMID: 30809568]
[http://dx.doi.org/10.1016/j.gore.2018.09.002] [PMID: 30246138]
[http://dx.doi.org/10.1158/1078-0432.CCR-14-1814] [PMID: 25500057]
[http://dx.doi.org/10.1007/978-3-319-91442-8_6] [PMID: 30069761]
[http://dx.doi.org/10.1016/j.ygyno.2014.01.008] [PMID: 24434059]
[http://dx.doi.org/10.1016/j.ygyno.2016.12.002] [PMID: 28062115]
[http://dx.doi.org/10.1136/esmoopen-2018-000444] [PMID: 30962959]
[PMID: 27822414]
[http://dx.doi.org/10.1158/2159-8290.CD-18-0444] [PMID: 30045908]
[http://dx.doi.org/10.1158/2159-8290.CD-15-0896] [PMID: 26732095]
[http://dx.doi.org/10.1186/s12935-019-0725-1] [PMID: 30636931]
[http://dx.doi.org/10.1002/path.2696] [PMID: 20229506]
[http://dx.doi.org/10.1002/cjp2.53] [PMID: 27840695]
[http://dx.doi.org/10.1038/sj.bjc.6603741] [PMID: 17437016]
[http://dx.doi.org/10.1038/s41598-019-41706-z] [PMID: 30918304]
[http://dx.doi.org/10.1136/ijgc-2018-000087] [PMID: 30659026]
[http://dx.doi.org/10.18632/oncotarget.24530] [PMID: 29662608]
[http://dx.doi.org/10.21873/anticanres.13149] [PMID: 30711931]
[http://dx.doi.org/10.1002/path.2744] [PMID: 20629008]
[http://dx.doi.org/10.1038/nm0302-282] [PMID: 11875500]
[http://dx.doi.org/10.1016/j.ejca.2017.06.023] [PMID: 28756138]
[http://dx.doi.org/10.1016/j.ccr.2012.03.042] [PMID: 22624712]
[http://dx.doi.org/10.1038/cddis.2015.143] [PMID: 26086967]
[http://dx.doi.org/10.1186/s13048-016-0239-6] [PMID: 27179933]
[http://dx.doi.org/10.1038/s41588-018-0179-8] [PMID: 30104763]
[http://dx.doi.org/10.1309/N6X5MB24BP42KP20] [PMID: 16753589]
[http://dx.doi.org/10.1158/1078-0432.CCR-08-1564] [PMID: 19193619]
[http://dx.doi.org/10.1097/CCO.0b013e32833b5126] [PMID: 20485165]
[http://dx.doi.org/10.1073/pnas.1314302110] [PMID: 24218601]
[http://dx.doi.org/10.1186/1757-2215-6-2] [PMID: 23289505]
[http://dx.doi.org/10.1186/s12885-019-5622-4] [PMID: 31060523]
[http://dx.doi.org/10.1038/s41598-017-16286-5] [PMID: 29170526]
[http://dx.doi.org/10.1016/S1470-2045(19)30154-8] [PMID: 31044723]
[http://dx.doi.org/10.1038/s41467-018-06130-3] [PMID: 30254278]
[http://dx.doi.org/10.1007/s13277-015-4299-9] [PMID: 26500096]
[http://dx.doi.org/10.1016/j.ygyno.2012.01.008] [PMID: 22261301]
[http://dx.doi.org/10.4161/cbt.5.10.3240] [PMID: 16969071]
[http://dx.doi.org/10.1097/PDM.0b013e3181359e1f] [PMID: 18303408]
[http://dx.doi.org/10.1093/annonc/mdq584] [PMID: 21098618]
[http://dx.doi.org/10.1016/j.ejca.2014.06.022] [PMID: 25087181]
[http://dx.doi.org/10.1200/JCO.18.00328] [PMID: 30339520]
[http://dx.doi.org/10.1017/erm.2018.5] [PMID: 30558693]
[http://dx.doi.org/10.1007/s00428-017-2222-z] [PMID: 28840321]
[http://dx.doi.org/10.1016/j.ajog.2005.01.054] [PMID: 16150257]
[http://dx.doi.org/10.1016/j.molonc.2014.12.003] [PMID: 25579085]
[http://dx.doi.org/10.3390/cancers11060774] [PMID: 31167492]
[http://dx.doi.org/10.1371/journal.pone.0145754] [PMID: 26717006]
[http://dx.doi.org/10.1371/journal.pmed.1002198] [PMID: 27997533]
[http://dx.doi.org/10.1593/neo.131900] [PMID: 24563622]
[http://dx.doi.org/10.1158/1078-0432.CCR-17-0544] [PMID: 28765325]
[http://dx.doi.org/10.1158/2159-8290.CD-17-0146] [PMID: 28450426]
[http://dx.doi.org/10.1097/MD.0000000000011505] [PMID: 30095616]
[http://dx.doi.org/10.1016/j.trsl.2018.10.003] [PMID: 30391474]
[http://dx.doi.org/10.1186/s13048-019-0482-8] [PMID: 30898156]
[http://dx.doi.org/10.18632/oncotarget.5766] [PMID: 26416421]
[http://dx.doi.org/10.1111/aogs.12883] [PMID: 26910180]
[http://dx.doi.org/10.18632/oncotarget.7850] [PMID: 26943577]
[http://dx.doi.org/10.1155/2017/3098542] [PMID: 28293063]
[http://dx.doi.org/10.1016/S1470-2045(16)30108-5] [PMID: 27402147]
[http://dx.doi.org/10.1016/S1470-2045(16)30149-8] [PMID: 27402146]
[http://dx.doi.org/10.1186/s40168-018-0483-7] [PMID: 29789015]
[http://dx.doi.org/10.3389/fmicb.2016.01144] [PMID: 27507964]
[http://dx.doi.org/10.1038/s41591-019-0377-7] [PMID: 30842679]
[http://dx.doi.org/10.1038/s41598-018-38031-2] [PMID: 30737418]
[http://dx.doi.org/10.1016/j.ygyno.2017.10.032] [PMID: 29128106]
[http://dx.doi.org/10.1080/02656736.2018.1518544] [PMID: 30295114]
[http://dx.doi.org/10.1016/j.ygyno.2016.03.010] [PMID: 26968641]
[http://dx.doi.org/10.1097/AOG.0000000000000981] [PMID: 26244529]
[http://dx.doi.org/10.1016/j.ygyno.2012.02.024] [PMID: 22366151]
[http://dx.doi.org/10.1186/s13073-018-0590-x] [PMID: 30382883]
[http://dx.doi.org/10.1016/j.ygyno.2015.11.009] [PMID: 26556769]
[http://dx.doi.org/10.1016/j.molonc.2014.05.017] [PMID: 24974076]
[http://dx.doi.org/10.1158/1078-0432.CCR-07-1083] [PMID: 18094425]
[http://dx.doi.org/10.1158/1078-0432.CCR-16-2615] [PMID: 28223274]
[http://dx.doi.org/10.1001/jamaoncol.2015.5495] [PMID: 26720728]
[http://dx.doi.org/10.1111/his.13711] [PMID: 30007074]
[http://dx.doi.org/10.1186/s13048-016-0234-y] [PMID: 27080533]
[http://dx.doi.org/10.1038/s41467-019-10460-1] [PMID: 31186408]
[http://dx.doi.org/10.1038/s41467-017-00263-7] [PMID: 28848242]
[http://dx.doi.org/10.1097/GCO.0000000000000243] [PMID: 26642065]
[http://dx.doi.org/10.1002/cjp2.109] [PMID: 30062862]
[http://dx.doi.org/10.1038/aps.2017.8] [PMID: 28414200]
[http://dx.doi.org/10.1056/NEJMoa1502309] [PMID: 26287849]
[http://dx.doi.org/10.1158/0008-5472.CAN-14-3569] [PMID: 26363007]
[http://dx.doi.org/10.1158/1078-0432.CCR-10-2307] [PMID: 21278246]
[http://dx.doi.org/10.1200/JCO.2015.61.2408] [PMID: 26261251]