Skip to content
2000
Volume 32, Issue 36
  • ISSN: 0929-8673
  • E-ISSN: 1875-533X

Abstract

Ovarian cancer (OC) ranks as the fifth leading cause of cancer-related deaths in the United States, posing a significant threat to female health. Late-stage diagnoses, driven by elusive symptoms often masquerading as gastrointestinal issues, contribute to a concerning 70% of cases being identified in advanced stages. While early-stage OC brags a 90% cure rate, progression involving pelvic organs or extending beyond the peritoneal cavity drastically diminishes it. Overcoming chemoresistance and metastasis requires a deep understanding of the associated progression mechanisms for innovative therapies. Extracellular vesicles (EVs), containing proteins, RNAs, DNAs, and metabolites, have surged in recent years, significantly impacting tumor progression, recurrence, immune evasion, and metastasis associated with the ovarian tumor microenvironment. Recent research unveils organ-specific metastatic patterns in OC, providing insights into tumor cell interactions and signaling crosstalk with stromal cells. The review explores the role of EVs behind OC cell metastasis and chemoresistance. Furthermore, the article delves into the role of EVs in the tumor microenvironment, immune evasion, and as biomarkers in context to OC, offering promising therapeutic strategies to enhance survival rates for OC patients. Lastly, the article focuses on an overview of PI3K/AKT/mTOR, MAPK/ERK, and VEGFR signaling pathways in the pathophysiology of ovarian cancer.

Loading

Article metrics loading...

/content/journals/cmc/10.2174/0109298673331849240930140120
2025-01-14
2025-10-29
Loading full text...

Full text loading...

References

  1. SiegelR.L. MillerK.D. WagleN.S. JemalA. Cancer statistics, 2023.CA Cancer J. Clin.2023731174810.3322/caac.2176336633525
    [Google Scholar]
  2. PiechockiM. KoziołekW. SrokaD. MatrejekA. MiziołekP. SaiukN. SledzikM. JaworskaA. BerezaK. PlutaE. BanasT. Trends in incidence and mortality of gynecological and breast cancers in Poland (1980–2018).Clin. Epidemiol.2022149511410.2147/CLEP.S33008135115839
    [Google Scholar]
  3. Brett MR. Brett MR. Jennifer BP. Thomas AS. Jennifer BP. Thomas AS. Epidemiology of ovarian cancer: A review.Cancer Biol. Med.201714193210.20892/j.issn.2095‑3941.2016.008428443200
    [Google Scholar]
  4. PfeifferR.M. ParkY. KreimerA.R. LaceyJ.V.Jr PeeD. GreenleeR.T. BuysS.S. HollenbeckA. RosnerB. GailM.H. HartgeP. Risk prediction for breast, endometrial, and ovarian cancer in white women aged 50 y or older: Derivation and validation from population-based cohort studies.PLoS Med.2013107e100149210.1371/journal.pmed.100149223935463
    [Google Scholar]
  5. Key statistics for ovarian cancer. 2024.Available from: https://www.cancer.org/cancer/types/ovarian-cancer/about/key-statistics.html
  6. Lino-SilvaL.S. Ovarian carcinoma: Pathology review with an emphasis in their molecular characteristics.Chin. Clin. Oncol.2020944510.21037/cco‑20‑3132434347
    [Google Scholar]
  7. BerekJ.S. RenzM. FriedlanderM.L. BastR.C.Jr Epithelial ovarian, fallopian tube, and peritoneal cancer.Holland-Frei Cancer MedicineWiley2024123
    [Google Scholar]
  8. YeungT.L. LeungC.S. YipK.P. Au YeungC.L. WongS.T.C. MokS.C. Cellular and molecular processes in ovarian cancer metastasis. A review in the theme: Cell and molecular processes in cancer metastasis.Am. J. Physiol. Cell Physiol.20153097C444C45610.1152/ajpcell.00188.201526224579
    [Google Scholar]
  9. LeongE. OngS.K. JaliF. NaingL. Incidence, mortality and survival analysis of epithelial ovarian cancer in brunei darussalam.Asian Pac. J. Cancer Prev.20222341415142310.31557/APJCP.2022.23.4.141535485704
    [Google Scholar]
  10. AroraT. MullangiS. LekkalaM.R. Ovarian cancer.StatPearls, StatPearls Publishing Copyright © 2024.StatPearls Publishing LLC2024
    [Google Scholar]
  11. CaoW. ChenH.D. YuY.W. LiN. ChenW.Q. Changing profiles of cancer burden worldwide and in China: A secondary analysis of the global cancer statistics 2020.Chin. Med. J.2021134778379110.1097/CM9.000000000000147433734139
    [Google Scholar]
  12. ArendR. MartinezA. SzulT. BirrerM.J. Biomarkers in ovarian cancer: To be or not to be.Cancer2019125S24Suppl. 244563457210.1002/cncr.3259531967683
    [Google Scholar]
  13. Devouassoux-ShisheboranM. GenestieC. Pathobiology of ovarian carcinomas.Chin. J. Cancer2015341505510.5732/cjc.014.1027325556618
    [Google Scholar]
  14. Ovarian cancer stages. 2018.Available from: https://www.cancer.org/cancer/types/ovarian-cancer/detection-diagnosis-staging/staging.html
  15. PratJ. FIGO Committee on Gynecologic Oncology FIGO’s staging classification for cancer of the ovary, fallopian tube, and peritoneum: Abridged republication.J. Gynecol. Oncol.2015262878910.3802/jgo.2015.26.2.8725872889
    [Google Scholar]
  16. BerekJ.S. RenzM. KehoeS. KumarL. FriedlanderM. Cancer of the ovary, fallopian tube, and peritoneum: 2021 update.Int. J. Gynaecol. Obstet.2021155S1618510.1002/ijgo.1387834669199
    [Google Scholar]
  17. CristS.B. GhajarC.M. When a house is not a home: A survey of antimetastatic niches and potential mechanisms of disseminated tumor cell suppression.Annu. Rev. Pathol.202116140943210.1146/annurev‑pathmechdis‑012419‑03264733276706
    [Google Scholar]
  18. KalluriR. LeBleuV.S. The biology, function, and biomedical applications of exosomes.Science20203676478eaau697710.1126/science.aau697732029601
    [Google Scholar]
  19. SrivastavaA. RathoreS. MunshiA. RameshR. Extracellular vesicles in oncology: From immune suppression to immunotherapy.AAPS J.20212323010.1208/s12248‑021‑00554‑433586060
    [Google Scholar]
  20. BradleyJ.A. BoltonE.M. PedersenR.A. Stem cell medicine encounters the immune system.Nat. Rev. Immunol.200221185987110.1038/nri93412415309
    [Google Scholar]
  21. LedermannJ.A. RajaF.A. FotopoulouC. Gonzalez- MartinA. ColomboN. SessaC. ESMO Guidelines Working Group Newly diagnosed and relapsed epithelial ovarian carcinoma: ESMO clinical practice guidelines for diagnosis, treatment and follow-up.Ann. Oncol.201324Suppl. 6vi24vi3210.1093/annonc/mdt33324078660
    [Google Scholar]
  22. ArmstrongD.K. AlvarezR.D. Bakkum-GamezJ.N. BarroilhetL. BehbakhtK. BerchuckA. BerekJ.S. ChenL. CristeaM. DeRosaM. ElNaggarA.C. GershensonD.M. GrayH.J. HakamA. JainA. JohnstonC. LeathC.A.III LiuJ. MahdiH. MateiD. McHaleM. McLeanK. O’MalleyD.M. PensonR.T. Percac-LimaS. RatnerE. RemmengaS.W. SabbatiniP. WernerT.L. ZsirosE. BurnsJ.L. EnghA.M. NCCN guidelines insights: Ovarian cancer, version 1.2019.J. Natl. Compr. Canc. Netw.201917889690910.6004/jnccn.2019.003931390583
    [Google Scholar]
  23. MontemoranoL. LightfootM. BixelK. Role of olaparib as maintenance treatment for ovarian cancer: The evidence to date.OncoTargets Ther.201912114971150610.2147/OTT.S19555231920338
    [Google Scholar]
  24. TewariK.S. BurgerR.A. EnserroD. NorquistB.M. SwisherE.M. BradyM.F. BookmanM.A. FlemingG.F. HuangH. HomesleyH.D. FowlerJ.M. GreerB.E. BoenteM. LiangS.X. YeC. BaisC. RandallL.M. ChanJ.K. FerrissJ.S. ColemanR.L. AghajanianC. HerzogT.J. DiSaiaP.J. CopelandL.J. MannelR.S. BirrerM.J. MonkB.J. Final overall survival of a randomized trial of bevacizumab for primary treatment of ovarian cancer.J. Clin. Oncol.201937262317232810.1200/JCO.19.0100931216226
    [Google Scholar]
  25. VarierL. SundaramS.M. GamitN. WarrierS. An overview of ovarian cancer: The role of cancer stem cells in chemoresistance and a precision medicine approach targeting the wnt pathway with the antagonist sFRP4.Cancers2023154127510.3390/cancers1504127536831617
    [Google Scholar]
  26. LiG. GongJ. CaoS. WuZ. ChengD. ZhuJ. HuangX. TangJ. YuanY. CaiW. ZhangH. The non-coding RNAs inducing drug resistance in ovarian cancer: A new perspective for understanding drug resistance.Front. Oncol.20211174214910.3389/fonc.2021.74214934660304
    [Google Scholar]
  27. AbdullahL.N. ChowE.K.H. Mechanisms of chemoresistance in cancer stem cells.Clin. Transl. Med.201321e310.1186/2001‑1326‑2‑323369605
    [Google Scholar]
  28. WangL. LiS. ZhuD. QinY. WangX. HongZ. HanZ. Effectiveness and safety of nab-paclitaxel and platinum as first-line chemotherapy for ovarian cancer: A retrospective study.J. Gynecol. Oncol.2023344e4410.3802/jgo.2023.34.e4436807747
    [Google Scholar]
  29. LisioM.A. FuL. GoyenecheA. GaoZ. TelleriaC. High-grade serous ovarian cancer: Basic sciences, clinical and therapeutic standpoints.Int. J. Mol. Sci.201920495210.3390/ijms2004095230813239
    [Google Scholar]
  30. TorreL.A. TrabertB. DeSantisC.E. MillerK.D. SamimiG. RunowiczC.D. GaudetM.M. JemalA. SiegelR.L. Ovarian cancer statistics, 2018.CA Cancer J. Clin.201868428429610.3322/caac.2145629809280
    [Google Scholar]
  31. TimmermansM. SonkeG.S. Van de VijverK.K. van der AaM.A. KruitwagenR.F.P.M. No improvement in long-term survival for epithelial ovarian cancer patients: A population-based study between 1989 and 2014 in the Netherlands.Eur. J. Cancer201888313710.1016/j.ejca.2017.10.03029179135
    [Google Scholar]
  32. MusiA. BongiovanniL. Extracellular vesicles in cancer drug resistance: Implications on melanoma therapy.Cancers2023154107410.3390/cancers1504107436831417
    [Google Scholar]
  33. YangQ. XuJ. GuJ. ShiH. ZhangJ. ZhangJ. ChenZ.S. FangX. ZhuT. ZhangX. Extracellular vesicles in cancer drug resistance: Roles, mechanisms, and implications.Adv. Sci.2022934220160910.1002/advs.20220160936253096
    [Google Scholar]
  34. ZhaoL. GuoH. ChenX. ZhangW. HeQ. DingL. YangB. Tackling drug resistance in ovarian cancer with epigenetic targeted drugs.Eur. J. Pharmacol.202292717507110.1016/j.ejphar.2022.17507135636522
    [Google Scholar]
  35. SafaeiR. LarsonB.J. ChengT.C. GibsonM.A. OtaniS. NaerdemannW. HowellS.B. Abnormal lysosomal trafficking and enhanced exosomal export of cisplatin in drug-resistant human ovarian carcinoma cells.Mol. Cancer Ther.20054101595160410.1158/1535‑7163.MCT‑05‑010216227410
    [Google Scholar]
  36. PiccioliniS. RodàF. BedoniM. GualerziA. Advances in the field of micro- and nanotechnologies applied to extracellular vesicle research: Take-home message from ISEV2021.Micromachines20211212156310.3390/mi1212156334945413
    [Google Scholar]
  37. PalviainenM. SaraswatM. VargaZ. KitkaD. NeuvonenM. PuhkaM. JoenvääräS. RenkonenR. NieuwlandR. TakataloM. SiljanderP.R.M. Extracellular vesicles from human plasma and serum are carriers of extravesicular cargo—Implications for biomarker discovery.PLoS One2020158e023643910.1371/journal.pone.023643932813744
    [Google Scholar]
  38. Ali SyedaZ. LangdenS.S.S. MunkhzulC. LeeM. SongS.J. Regulatory mechanism of MicroRNA expression in cancer.Int. J. Mol. Sci.2020215172310.3390/ijms2105172332138313
    [Google Scholar]
  39. SamuelP. MulcahyL. A. FurlongF. McCarthyH. O. BrooksS. A. FabbriM. PinkR. C. CarterD. R. F. Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells.Philos. Trans. R. Soc. Lond. B Biol. Sci.2018373173710.1098/rstb.2017.0065
    [Google Scholar]
  40. Asare-WereheneM. CommunalL. CarmonaE. HanY. SongY.S. BurgerD. Mes-MassonA.M. TsangB.K. Plasma gelsolin inhibits CD8+ T-cell function and regulates glutathione production to confer chemoresistance in ovarian cancer.Cancer Res.202080183959397110.1158/0008‑5472.CAN‑20‑078832641415
    [Google Scholar]
  41. ZhangF. ZhuY. ZhaoQ. YangD. DongY. JiangL. XingW. LiX. XingH. ShiM. ChenY. BruceI.C. JinJ. MaX. Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance.Eur. J. Pharmacol.2014738839010.1016/j.ejphar.2014.05.02624877693
    [Google Scholar]
  42. SchweerD. McAteeA. NeupaneK. RichardsC. UelandF. KolesarJ. Tumor-associated macrophages and ovarian cancer: Implications for therapy.Cancers2022149222010.3390/cancers1409222035565348
    [Google Scholar]
  43. WangW. HanD. SongY. S. Abstract 5081: Proteomic analysis of ascites- and cancer cell-derived EVs for identifying ovarian cancer diagnostic biomarkers.Cancer Research20228212_Supplement5081508110.1158/1538‑7445.AM2022‑5081
    [Google Scholar]
  44. Asare-WereheneM. HunterR.A. GerberE. ReunovA. BrineI. ChangC.Y. ChangC.C. ShiehD.B. BurgerD. AnisH. TsangB.K. The application of an extracellular vesicle-based biosensor in early diagnosis and prediction of chemoresponsiveness in ovarian cancer.Cancers2023159256610.3390/cancers1509256637174032
    [Google Scholar]
  45. HosseinikhahS.M. GheybiF. MoosavianS.A. ShahbaziM.A. JaafariM.R. SillanpääM. KesharwaniP. AlavizadehS.H. SahebkarA. Role of exosomes in tumour growth, chemoresistance and immunity: State-of-the-art.J. Drug Target.2023311325010.1080/1061186X.2022.211400035971773
    [Google Scholar]
  46. GuoQ. WangH. YanY. LiuY. SuC. ChenH. YanY. AdhikariR. WuQ. ZhangJ. The role of exosomal microrna in cancer drug resistance.Front. Oncol.20201047210.3389/fonc.2020.0047232318350
    [Google Scholar]
  47. GrixtiJ.M. AyersD. DayP.J.R. An analysis of mechanisms for cellular uptake of mirnas to enhance drug delivery and efficacy in cancer chemoresistance.Noncoding RNA2021722710.3390/ncrna702002733923485
    [Google Scholar]
  48. AlharbiM. SharmaS. GuanzonD. LaiA. ZuñigaF. ShiddikyM.J.A. YamauchiY. Salas-BurgosA. HeY. PejovicT. WintersC. MorganT. PerrinL. HooperJ.D. SalomonC. miRNa signature in small extracellular vesicles and their association with platinum resistance and cancer recurrence in ovarian cancer.Nanomedicine20202810220710.1016/j.nano.2020.10220732334098
    [Google Scholar]
  49. Au YeungC.L. CoN.N. TsurugaT. YeungT.L. KwanS.Y. LeungC.S. LiY. LuE.S. KwanK. WongK.K. SchmandtR. LuK.H. MokS.C. Exosomal transfer of stroma-derived miR21 confers paclitaxel resistance in ovarian cancer cells through targeting APAF1.Nat. Commun.2016711115010.1038/ncomms1115027021436
    [Google Scholar]
  50. GuoH. HaC. DongH. YangZ. MaY. DingY. Cancer-associated fibroblast-derived exosomal microRNA-98-5p promotes cisplatin resistance in ovarian cancer by targeting CDKN1A.Cancer Cell Int.201919134710.1186/s12935‑019‑1051‑331889899
    [Google Scholar]
  51. ZhuX. ShenH. YinX. YangM. WeiH. ChenQ. FengF. LiuY. XuW. LiY. Macrophages derived exosomes deliver miR-223 to epithelial ovarian cancer cells to elicit a chemoresistant phenotype.J. Exp. Clin. Cancer Res.20193818110.1186/s13046‑019‑1095‑130770776
    [Google Scholar]
  52. KanlikilicerP. BayraktarR. DenizliM. RashedM.H. IvanC. AslanB. MitraR. KaragozK. BayraktarE. ZhangX. Rodriguez-AguayoC. El-ArabeyA.A. KahramanN. BaydoganS. OzkayarO. GatzaM.L. OzpolatB. CalinG.A. SoodA.K. Lopez-BeresteinG. Corrigendum to ‘Exosomal miRNA confers chemo resistance via targeting Cav1/p-gp/M2-type macrophage axis in ovarian cancer’ [EBioMedicine 38 (2018) 100–112].EBioMedicine20205210263010.1016/j.ebiom.2020.10263031972470
    [Google Scholar]
  53. Weiner-GorzelK. DempseyE. MilewskaM. McGoldrickA. TohV. WalshA. LindsayS. GubbinsL. CannonA. SharpeD. O’SullivanJ. MurphyM. MaddenS.F. KellM. McCannA. FurlongF. Overexpression of the microRNA miR-433 promotes resistance to paclitaxel through the induction of cellular senescence in ovarian cancer cells.Cancer Med.20154574575810.1002/cam4.40925684390
    [Google Scholar]
  54. XieZ. CaoL. ZhangJ. miR-21 modulates paclitaxel sensitivity and hypoxia-inducible factor-1α expression in human ovarian cancer cells.Oncol. Lett.20136379580010.3892/ol.2013.143224137413
    [Google Scholar]
  55. DavidsonB. TropéC.G. ReichR. The clinical and diagnostic role of microRNAs in ovarian carcinoma.Gynecol. Oncol.2014133364064610.1016/j.ygyno.2014.03.57524713546
    [Google Scholar]
  56. WangY. BaoW. LiuY. WangS. XuS. LiX. LiY. WuS. miR-98-5p contributes to cisplatin resistance in epithelial ovarian cancer by suppressing miR-152 biogenesis via targeting Dicer1.Cell Death Dis.20189544710.1038/s41419‑018‑0390‑729670086
    [Google Scholar]
  57. ChenC. WangH.J. YangL.Y. JiaX.B. XuP. ChenJ. LiuY. Expression of miR-130a in serum samples of patients with epithelial ovarian cancer and its association with platinum resistance.Sichuan Da Xue Xue Bao Yi Xue Ban2016471606327062783
    [Google Scholar]
  58. PinkR.C. SamuelP. MassaD. CaleyD.P. BrooksS.A. CarterD.R.F. The passenger strand, miR-21-3p, plays a role in mediating cisplatin resistance in ovarian cancer cells.Gynecol. Oncol.2015137114315110.1016/j.ygyno.2014.12.04225579119
    [Google Scholar]
  59. JiangY. JiangJ. JiaH. QiaoZ. ZhangJ. Recovery of miR-139-5p in ovarian cancer reverses cisplatin resistance by targeting C-Jun.Cell. Physiol. Biochem.201851112914110.1159/00049516930439707
    [Google Scholar]
  60. YangC. KimH.S. ParkS.J. LeeE.J. KimS.I. SongG. LimW. Inhibition of miR-214-3p aids in preventing epithelial ovarian cancer malignancy by increasing the expression of LHX6.Cancers20191112191710.3390/cancers1112191731810245
    [Google Scholar]
  61. YangH. KongW. HeL. ZhaoJ.J. O’DonnellJ.D. WangJ. WenhamR.M. CoppolaD. KrukP.A. NicosiaS.V. ChengJ.Q. MicroRNA expression profiling in human ovarian cancer: miR-214 induces cell survival and cisplatin resistance by targeting PTEN.Cancer Res.200868242543310.1158/0008‑5472.CAN‑07‑248818199536
    [Google Scholar]
  62. GuoP. XiongX. ZhangS. PengD. miR-100 resensitizes resistant epithelial ovarian cancer to cisplatin.Oncol. Rep.20163663552355810.3892/or.2016.514027748936
    [Google Scholar]
  63. LiZ. NiuH. QinQ. YangS. WangQ. YuC. WeiZ. JinZ. WangX. YangA. ChenX. lncRNA UCA1 mediates resistance to cisplatin by regulating the miR-143/FOSL2-signaling pathway in ovarian cancer.Mol. Ther. Nucleic Acids2019179210110.1016/j.omtn.2019.05.00731234009
    [Google Scholar]
  64. HanX. ZhenS. YeZ. LuJ. WangL. LiP. LiJ. ZhengX. LiH. ChenW. ZhaoL. LiX. A feedback loop between miR-30a/c-5p and DNMT1 mediates cisplatin resistance in ovarian cancer cells.Cell. Physiol. Biochem.201741397398610.1159/00046061828222434
    [Google Scholar]
  65. a AboutalebiH. BahramiA. SoleimaniA. SaeediN. RahmaniF. KhazaeiM. FiujiH. ShafieeM. FernsG. A. AvanA. The diagnostic, prognostic and therapeutic potential of circulating microRNAs in ovarian cancer.Int J Biochem Cell Biol 202012410576510.1016/j.biocel.2020.105765
    [Google Scholar]
  66. b PanC. StevicI. MüllerV. NiQ. Oliveira-FerrerL. PantelK. SchwarzenbachH. Exosomal microRNAs as tumor markers in epithelial ovarian cancer.Mol. Oncol.2018Nov 12111935194810.1002/1878‑0261.12371
    [Google Scholar]
  67. ZhangW. SuX. LiS. LiuZ. WangQ. ZengH. Low serum exosomal miR-484 expression predicts unfavorable prognosis in ovarian cancer.Cancer Biomark.202027448549110.3233/CBM‑19112332065786
    [Google Scholar]
  68. LiS. MaF. JiangK. ShanH. ShiM. ChenB. Long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 promotes lung adenocarcinoma by directly interacting with specificity protein 1.Cancer Sci.201810951346135610.1111/cas.1358729575609
    [Google Scholar]
  69. ZhaoM. WangS. LiQ. JiQ. GuoP. LiuX. MALAT1: A long non-coding RNA highly associated with human cancers (Review).Oncol. Lett.2018161192610.3892/ol.2018.861329928382
    [Google Scholar]
  70. AmodioN. RaimondiL. JuliG. StamatoM.A. CaraccioloD. TagliaferriP. TassoneP. MALAT1: A druggable long non-coding RNA for targeted anti-cancer approaches.J. Hematol. Oncol.20181116310.1186/s13045‑018‑0606‑429739426
    [Google Scholar]
  71. WangH. WangL. ZhangG. LuC. ChuH. YangR. ZhaoG. MALAT1/miR-101-3p/MCL1 axis mediates cisplatin resistance in lung cancer.Oncotarget2018977501751210.18632/oncotarget.2348329484127
    [Google Scholar]
  72. ChenQ. WeiC. WangZ. SunM. Long non-coding RNAs in anti-cancer drug resistance.Oncotarget2017811925193610.18632/oncotarget.1246127713133
    [Google Scholar]
  73. ZhaoZ. JiM. WangQ. HeN. LiY. RETRACTED: Circular RNA Cdr1as upregulates SCAI to suppress cisplatin resistance in ovarian cancer via miR-1270 suppression.Mol. Ther. Nucleic Acids201918243310.1016/j.omtn.2019.07.01231479922
    [Google Scholar]
  74. GerberE. Asare-WereheneM. ReunovA. BurgerD. LeT. CarmonaE. Mes-MassonA.M. TsangB.K. Predicting chemoresponsiveness in epithelial ovarian cancer patients using circulating small extracellular vesicle-derived plasma gelsolin.J. Ovarian Res.20231611410.1186/s13048‑022‑01086‑x36642715
    [Google Scholar]
  75. SharmaS. AlharbiM. KobayashiM. LaiA. GuanzonD. ZuñigaF. OrmazabalV. PalmaC. Scholz-RomeroK. RiceG.E. HooperJ.D. SalomonC. Proteomic analysis of exosomes reveals an association between cell invasiveness and exosomal bioactivity on endothelial and mesenchymal cell migration in vitro.Clin. Sci.2018132182029204410.1042/CS2018042530219799
    [Google Scholar]
  76. ZhouW. FongM.Y. MinY. SomloG. LiuL. PalomaresM.R. YuY. ChowA. O’ConnorS.T.F. ChinA.R. YenY. WangY. MarcussonE.G. ChuP. WuJ. WuX. LiA.X. LiZ. GaoH. RenX. BoldinM.P. LinP.C. WangS.E. Cancer-secreted miR-105 destroys vascular endothelial barriers to promote metastasis.Cancer Cell201425450151510.1016/j.ccr.2014.03.00724735924
    [Google Scholar]
  77. KanlikilicerP. RashedM.H. BayraktarR. MitraR. IvanC. AslanB. ZhangX. FilantJ. SilvaA.M. Rodriguez-AguayoC. BayraktarE. PichlerM. OzpolatB. CalinG.A. SoodA.K. Lopez-BeresteinG. Ubiquitous release of exosomal tumor suppressor miR-6126 from ovarian cancer cells.Cancer Res.201676247194720710.1158/0008‑5472.CAN‑16‑071427742688
    [Google Scholar]
  78. LiX. LiuR. WangZ. WuM. ChangL. YuanH. ZhuangF. SongY. LiuZ. MicroRNA-7 regulates the proliferation and metastasis of human papillary carcinoma cells by targeting Bcl-2.Am. J. Transl. Res.20201295772578033042456
    [Google Scholar]
  79. RezaA.M.M.T. ChoiY.J. YasudaH. KimJ.H. Human adipose mesenchymal stem cell-derived exosomal-miRNAs are critical factors for inducing anti-proliferation signalling to A2780 and SKOV-3 ovarian cancer cells.Sci. Rep.2016613849810.1038/srep3849827929108
    [Google Scholar]
  80. GiustiI. Di FrancescoM. PoppaG. EspositoL. D’AscenzoS. DoloV. Tumor-derived extracellular vesicles activate normal human fibroblasts to a cancer-associated fibroblast-like phenotype, sustaining a pro-tumorigenic microenvironment.Front. Oncol.20221283988010.3389/fonc.2022.83988035280782
    [Google Scholar]
  81. LuoY. GuiR. Circulating exosomal circFoxp1 confers cisplatin resistance in epithelial ovarian cancer cells.J. Gynecol. Oncol.2020315e7510.3802/jgo.2020.31.e7532808501
    [Google Scholar]
  82. BarkalA.A. BrewerR.E. MarkovicM. KowarskyM. BarkalS.A. ZaroB.W. KrishnanV. HatakeyamaJ. DorigoO. BarkalL.J. WeissmanI.L. CD24 signalling through macrophage Siglec-10 is a target for cancer immunotherapy.Nature2019572776939239610.1038/s41586‑019‑1456‑031367043
    [Google Scholar]
  83. WangH. LiuB. WeiJ. Beta2-microglobulin(B2M) in cancer immunotherapies: Biological function, resistance and remedy.Cancer Lett.20215179610410.1016/j.canlet.2021.06.00834129878
    [Google Scholar]
  84. WangY. XiangY. XinV.W. WangX.W. PengX.C. LiuX.Q. WangD. LiN. ChengJ.T. LyvY.N. CuiS.Z. MaZ. ZhangQ. XinH.W. Dendritic cell biology and its role in tumor immunotherapy.J. Hematol. Oncol.202013110710.1186/s13045‑020‑00939‑632746880
    [Google Scholar]
  85. JiangH. AwutiG. GuoX. Construction of an immunophenoscore-related signature for evaluating prognosis and immunotherapy sensitivity in ovarian cancer.ACS Omega2023836330173303110.1021/acsomega.3c0485637720747
    [Google Scholar]
  86. WuF. GuY. KangB. HeskiaF. PachotA. BonnevilleM. WeiP. LiangJ. PD-L1 detection on circulating tumor-derived extracellular vesicles (T-EVs) from patients with lung cancer.Transl. Lung Cancer Res.20211062441245110.21037/tlcr‑20‑127734295653
    [Google Scholar]
  87. HanY. LiuD. LiL. PD-1/PD-L1 pathway: Current researches in cancer.Am. J. Cancer Res.202010372774232266087
    [Google Scholar]
  88. BasakU. SarkarT. MukherjeeS. ChakrabortyS. DuttaA. DuttaS. NayakD. KaushikS. DasT. SaG. Tumor-associated macrophages: An effective player of the tumor microenvironment.Front. Immunol.202314129525710.3389/fimmu.2023.129525738035101
    [Google Scholar]
  89. ChenX. YingX. WangX. WuX. ZhuQ. WangX. Exosomes derived from hypoxic epithelial ovarian cancer deliver microRNA-940 to induce macrophage M2 polarization.Oncol. Rep.201738152252810.3892/or.2017.569728586039
    [Google Scholar]
  90. LiH. FanX. HoughtonJ. Tumor microenvironment: The role of the tumor stroma in cancer.J. Cell. Biochem.2007101480581510.1002/jcb.2115917226777
    [Google Scholar]
  91. XuW.X. WangD.D. ZhaoZ.Q. ZhangH.D. YangS.J. ZhangQ. LiL. ZhangJ. Exosomal microRNAs shuttling between tumor cells and macrophages: Cellular interactions and novel therapeutic strategies.Cancer Cell Int.202222119010.1186/s12935‑022‑02594‑y35578228
    [Google Scholar]
  92. TanS. TangH. WangY. XieP. LiH. ZhangZ. ZhouJ. Tumor cell-derived exosomes regulate macrophage polarization: Emerging directions in the study of tumor genesis and development.Heliyon202399e1929610.1016/j.heliyon.2023.e1929637662730
    [Google Scholar]
  93. ZhouY. RenH. DaiB. LiJ. ShangL. HuangJ. ShiX. Hepatocellular carcinoma-derived exosomal miRNA-21 contributes to tumor progression by converting hepatocyte stellate cells to cancer-associated fibroblasts.J. Exp. Clin. Cancer Res.201837132410.1186/s13046‑018‑0965‑230591064
    [Google Scholar]
  94. FedericiC. ShahajE. CecchettiS. CameriniS. CasellaM. IessiE. CamisaschiC. PaolinoG. CalvieriS. FerroS. Natural-killer-derived extracellular vesicles: Immune sensors and interactors.Front Immunol.20201126210.3389/fimmu.2020.00262
    [Google Scholar]
  95. GorelikM. Frischmeyer-GuerrerioP.A. Innate and adaptive dendritic cell responses to immunotherapy.Curr. Opin. Allergy Clin. Immunol.201515657558010.1097/ACI.000000000000021326509662
    [Google Scholar]
  96. DingG. ZhouL. QianY. FuM. ChenJ. ChenJ. XiangJ. WuZ. JiangG. CaoL. Pancreatic cancer-derived exosomes transfer miRNAs to dendritic cells and inhibit RFXAP expression via miR-212-3p.Oncotarget2015630298772988810.18632/oncotarget.492426337469
    [Google Scholar]
  97. Lawrence MJ.Y. GuoY. ChenZ. WangY. YangC. DudasA. DuZ. LiuW. ZouY. SzaboE. LeeS.C. SimsM. GuW. TillmannsT. PfefferL.M. TigyiG. YueJ. miR-203 functions as a tumor suppressor by inhibiting epithelial to mesenchymal transition in ovarian cancer.J. Cancer Sci. Ther.201572344310.4172/1948‑5956.100032226819680
    [Google Scholar]
  98. ShenY. GuoD. WengL. WangS. MaZ. YangY. WangP. WangJ. CaiZ. Tumor-derived exosomes educate dendritic cells to promote tumor metastasis via HSP72/HSP105-TLR2/TLR4 pathway.OncoImmunology2017612e136252710.1080/2162402X.2017.136252729209566
    [Google Scholar]
  99. LaneD. MatteI. RancourtC. PichéA. The prosurvival activity of ascites against TRAIL is associated with a shorter disease-free interval in patients with ovarian cancer.J. Ovarian Res.201031110.1186/1757‑2215‑3‑120157422
    [Google Scholar]
  100. Czystowska-KuzmiczM. SosnowskaA. NowisD. RamjiK. SzajnikM. Chlebowska-TuzJ. WolinskaE. GajP. GrazulM. PilchZ. ZerrouqiA. Graczyk- JarzynkaA. SoroczynskaK. CierniakS. KoktyszR. ElishaevE. GrucaS. StefanowiczA. BlaszczykR. BorekB. GzikA. WhitesideT. GolabJ. Small extracellular vesicles containing arginase-1 suppress T-cell responses and promote tumor growth in ovarian carcinoma.Nat. Commun.2019101300010.1038/s41467‑019‑10979‑331278254
    [Google Scholar]
  101. TaylorD.D. Gerçel-TaylorC. LyonsK.S. StansonJ. WhitesideT.L. T-cell apoptosis and suppression of T-cell receptor/CD3-zeta by Fas ligand-containing membrane vesicles shed from ovarian tumors.Clin. Cancer Res.20039145113511914613988
    [Google Scholar]
  102. KlinkerM. W. LizzioV. ReedT. J. FoxD. A. LundyS. K. Human B cell-derived lymphoblastoid cell lines constitutively produce fas ligand and secrete MHCII(+)FasL(+) killer exosomes.Front Immunol.2014514410.3389/fimmu.2014.00144
    [Google Scholar]
  103. TkachM. KowalJ. ZucchettiA.E. EnserinkL. JouveM. LankarD. SaitakisM. Martin-JaularL. ThéryC. Qualitative differences in T-cell activation by dendritic cell-derived extracellular vesicle subtypes.EMBO J.201736203012302810.15252/embj.20169600328923825
    [Google Scholar]
  104. LiuC. YuS. ZinnK. WangJ. ZhangL. JiaY. KappesJ.C. BarnesS. KimberlyR.P. GrizzleW.E. ZhangH.G. Murine mammary carcinoma exosomes promote tumor growth by suppression of NK cell function.J. Immunol.200617631375138510.4049/jimmunol.176.3.137516424164
    [Google Scholar]
  105. LearyN. WalserS. HeY. CousinN. PereiraP. GalloA. Collado-DiazV. HalinC. Garcia-SilvaS. PeinadoH. DieterichL.C. Melanoma-derived extracellular vesicles mediate lymphatic remodelling and impair tumour immunity in draining lymph nodes.J. Extracell. Vesicles2022112e1219710.1002/jev2.1219735188342
    [Google Scholar]
  106. Shoae-HassaniA. HamidiehA.A. BehfarM. MohseniR. Mortazavi-TabatabaeiS.A. AsgharzadehS. NK cell–derived exosomes from NK cells previously exposed to neuroblastoma cells augment the antitumor activity of cytokine-activated NK cells.J. Immunother.201740726527610.1097/CJI.000000000000017928622272
    [Google Scholar]
  107. AhmedN. StenversK.L. Getting to know ovarian cancer ascites: Opportunities for targeted therapy-based translational research.Front. Oncol.2013325610.3389/fonc.2013.0025624093089
    [Google Scholar]
  108. HosseiniR. SarvnazH. ArabpourM. RamsheS.M. Asef-KabiriL. YousefiH. AkbariM.E. EskandariN. Cancer exosomes and natural killer cells dysfunction: Biological roles, clinical significance and implications for immunotherapy.Mol. Cancer20222111510.1186/s12943‑021‑01492‑735031075
    [Google Scholar]
  109. KriegeskorteA.K. GebhardtF.E. PorcelliniS. SchiemannM. StembergerC. FranzT.J. HusterK.M. CarayannopoulosL.N. YokoyamaW.M. ColonnaM. SiccardiA.G. BauerS. BuschD.H. NKG2D-independent suppression of T cell proliferation by H60 and MICA.Proc. Natl. Acad. Sci. USA200510233118051181010.1073/pnas.050202610216091471
    [Google Scholar]
  110. KondělkováK. VokurkováD. KrejsekJ. BorskáL. FialaZ. AndrýsC. Regulatory T cells (TREG) and their roles in immune system with respect to immunopathological disorders.Acta Med.2010532737710.14712/18059694.2016.6320672742
    [Google Scholar]
  111. TangD. LiuS. ShenH. DengG. ZengS. Extracellular vesicles promote the formation of pre-metastasis niche in gastric cancer.Front. Immunol.20221381301510.3389/fimmu.2022.81301535173726
    [Google Scholar]
  112. XieF. ZhouX. FangM. LiH. SuP. TuY. ZhangL. ZhouF. Extracellular vesicles in cancer immune microenvironment and cancer immunotherapy.Adv. Sci.2019624190177910.1002/advs.20190177931871860
    [Google Scholar]
  113. YeL. ZhangQ. ChengY. ChenX. WangG. ShiM. ZhangT. CaoY. PanH. ZhangL. WangG. DengY. YangY. ChenG. Tumor-derived exosomal HMGB1 fosters hepatocellular carcinoma immune evasion by promoting TIM-1+ regulatory B cell expansion.J. Immunother. Cancer20186114510.1186/s40425‑018‑0451‑630526680
    [Google Scholar]
  114. ChenG. HuangA.C. ZhangW. ZhangG. WuM. XuW. YuZ. YangJ. WangB. SunH. XiaH. ManQ. ZhongW. AnteloL.F. WuB. XiongX. LiuX. GuanL. LiT. LiuS. YangR. LuY. DongL. McGettiganS. SomasundaramR. RadhakrishnanR. MillsG. LuY. KimJ. ChenY.H. DongH. ZhaoY. KarakousisG.C. MitchellT.C. SchuchterL.M. HerlynM. WherryE.J. XuX. GuoW. Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.Nature2018560771838238610.1038/s41586‑018‑0392‑830089911
    [Google Scholar]
  115. ShenoyG.N. LoyallJ. BerensonC.S. KelleherR.J.Jr IyerV. Balu-IyerS.V. OdunsiK. BankertR.B. Sialic acid–dependent inhibition of T cells by exosomal ganglioside GD3 in ovarian tumor microenvironments.J. Immunol.2018201123750375810.4049/jimmunol.180104130446565
    [Google Scholar]
  116. ChenS.W. ZhuS.Q. PeiX. QiuB.Q. XiongD. LongX. LinK. LuF. XuJ.J. WuY.B. Cancer cell-derived exosomal circUSP7 induces CD8+ T cell dysfunction and anti-PD1 resistance by regulating the miR-934/SHP2 axis in NSCLC.Mol. Cancer202120114410.1186/s12943‑021‑01448‑x34753486
    [Google Scholar]
  117. LiY. ZhouJ. ZhuoQ. ZhangJ. XieJ. HanS. ZhaoS. Malignant ascite-derived extracellular vesicles inhibit T cell activity by upregulating Siglec-10 expression.Cancer Manag. Res.2019117123713410.2147/CMAR.S21056831534365
    [Google Scholar]
  118. WangH. PanJ. BarskyL. JacobJ.C. ZhengY. GaoC. WangS. ZhuW. SunH. LuL. JiaH. ZhaoY. BrunsC. VagoR. DongQ. QinL. Characteristics of pre-metastatic niche: The landscape of molecular and cellular pathways.Mol. Biomed.202121310.1186/s43556‑020‑00022‑z35006432
    [Google Scholar]
  119. LiangB. PengP. ChenS. LiL. ZhangM. CaoD. YangJ. LiH. GuiT. LiX. ShenK. Characterization and proteomic analysis of ovarian cancer-derived exosomes.J. Proteomics20138017118210.1016/j.jprot.2012.12.02923333927
    [Google Scholar]
  120. TodorovaD. SimonciniS. LacroixR. SabatierF. Dignat-GeorgeF. Extracellular vesicles in angiogenesis.Circ. Res.2017120101658167310.1161/CIRCRESAHA.117.30968128495996
    [Google Scholar]
  121. LiuS. JiangM. ZhaoQ. LiS. PengY. ZhangP. HanM. Vascular endothelial growth factor plays a critical role in the formation of the pre-metastatic niche via prostaglandin E2.Oncol. Rep.20143262477248410.3892/or.2014.351625333935
    [Google Scholar]
  122. ThuaultS. GhossoubR. DavidG. ZimmermannP. A journey on extracellular vesicles for matrix metalloproteinases: A mechanistic perspective.Front. Cell Dev. Biol.20221088638110.3389/fcell.2022.88638135669514
    [Google Scholar]
  123. GiustiI. PoppaG. Di FazioG. D’AscenzoS. DoloV. Metastatic dissemination: Role of tumor-derived extracellular vesicles and their use as clinical biomarkers.Int. J. Mol. Sci.20232411959010.3390/ijms2411959037298540
    [Google Scholar]
  124. SchmidtA. OberleN. KrammerP.H. Molecular mechanisms of treg-mediated T cell suppression.Front. Immunol.201235110.3389/fimmu.2012.0005122566933
    [Google Scholar]
  125. RahmanM.J. RegnD. BashratyanR. DaiY.D. Exosomes released by islet-derived mesenchymal stem cells trigger autoimmune responses in NOD mice.Diabetes20146331008102010.2337/db13‑085924170696
    [Google Scholar]
  126. KarnasE. DudekP. Zuba-SurmaE.K. Stem cell- derived extracellular vesicles as new tools in regenerative medicine - Immunomodulatory role and future perspectives.Front. Immunol.202314112017510.3389/fimmu.2023.112017536761725
    [Google Scholar]
  127. TaichmanR.S. CooperC. KellerE.T. PientaK.J. TaichmanN.S. McCauleyL.K. Use of the stromal cell-derived factor-1/CXCR4 pathway in prostate cancer metastasis to bone.Cancer Res.20026261832183711912162
    [Google Scholar]
  128. ShelkeG.V. YinY. JangS.C. LässerC. WennmalmS. HoffmannH.J. LiL. GhoY.S. NilssonJ.A. LötvallJ. Endosomal signalling via exosome surface TGFβ-1.J. Extracell. Vesicles201981165045810.1080/20013078.2019.165045831595182
    [Google Scholar]
  129. GurunathanS. KangM.H. QasimM. KhanK. KimJ.H. Biogenesis, membrane trafficking, functions, and next generation nanotherapeutics medicine of extracellular vesicles.Int. J. Nanomedicine2021163357338310.2147/IJN.S31035734040369
    [Google Scholar]
  130. MohanA. AgarwalS. ClaussM. BrittN.S. DhillonN.K. Extracellular vesicles: Novel communicators in lung diseases.Respir. Res.202021117510.1186/s12931‑020‑01423‑y32641036
    [Google Scholar]
  131. GangadaranP. MadhyasthaH. MadhyasthaR. RajendranR.L. NakajimaY. WatanabeN. VelikkakathA.K.G. HongC.M. GopiR.V. MuthukaliananG.K. Valsala GopalakrishnanA. JeyaramanM. AhnB-C. The emerging role of exosomes in innate immunity, diagnosis and therapy.Front. Immunol.202313108505710.3389/fimmu.2022.1085057
    [Google Scholar]
  132. JinY. MaL. ZhangW. YangW. FengQ. WangH. Extracellular signals regulate the biogenesis of extracellular vesicles.Biol. Res.20225513510.1186/s40659‑022‑00405‑236435789
    [Google Scholar]
  133. SurmanM. StępieńE. Hoja-ŁukowiczD. PrzybyłoM. Deciphering the role of ectosomes in cancer development and progression: Focus on the proteome.Clin. Exp. Metastasis2017343-427328910.1007/s10585‑017‑9844‑z28317069
    [Google Scholar]
  134. JaiswalR. SedgerL.M. Intercellular vesicular transfer by exosomes, microparticles and oncosomes - Implications for cancer biology and treatments.Front. Oncol.2019912510.3389/fonc.2019.0012530895170
    [Google Scholar]
  135. MinciacchiV.R. YouS. SpinelliC. MorleyS. ZandianM. AspuriaP.J. CavalliniL. CiardielloC. SobreiroM.R. MorelloM. KharmateG. JangS.C. KimD.K. Hosseini-BeheshtiE. GunsE.T. GleaveM. GhoY.S. MathivananS. YangW. FreemanM.R. Di VizioD. Large oncosomes contain distinct protein cargo and represent a separate functional class of tumor-derived extracellular vesicles.Oncotarget2015613113271134110.18632/oncotarget.359825857301
    [Google Scholar]
  136. DixsonA.C. DawsonT.R. Di VizioD. WeaverA.M. Context-specific regulation of extracellular vesicle biogenesis and cargo selection.Nat. Rev. Mol. Cell Biol.202324745447610.1038/s41580‑023‑00576‑036765164
    [Google Scholar]
  137. ZouX. LeiQ. LuoX. YinJ. chenS. HaoC. ShiyuL. MaD. Advances in biological functions and applications of apoptotic vesicles.Cell Commun. Signal.202321126010.1186/s12964‑023‑01251‑937749626
    [Google Scholar]
  138. O’BrienK. BreyneK. UghettoS. LaurentL.C. BreakefieldX.O. RNA delivery by extracellular vesicles in mammalian cells and its applications.Nat. Rev. Mol. Cell Biol.2020211058560610.1038/s41580‑020‑0251‑y32457507
    [Google Scholar]
  139. KatoM. NatarajanR. MicroRNA circuits in transforming growth factor-β actions and diabetic nephropathy.Semin. Nephrol.201232325326010.1016/j.semnephrol.2012.04.00422835456
    [Google Scholar]
  140. PegtelD.M. CosmopoulosK. Thorley-LawsonD.A. van EijndhovenM.A.J. HopmansE.S. LindenbergJ.L. de GruijlT.D. WürdingerT. MiddeldorpJ.M. Functional delivery of viral miRNAs via exosomes.Proc. Natl. Acad. Sci. USA2010107146328633310.1073/pnas.091484310720304794
    [Google Scholar]
  141. ParkS.M. GaurA.B. LengyelE. PeterM.E. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2.Genes Dev.200822789490710.1101/gad.164060818381893
    [Google Scholar]
  142. HaslehurstA.M. KotiM. DharseeM. NuinP. EvansK. GeraciJ. ChildsT. ChenJ. LiJ. WeberpalsJ. DaveyS. SquireJ. ParkP.C. FeilotterH. EMT transcription factors snail and slug directly contribute to cisplatin resistance in ovarian cancer.BMC Cancer20121219110.1186/1471‑2407‑12‑9122429801
    [Google Scholar]
  143. MediciD. HayE.D. OlsenB.R. Snail and Slug promote epithelial-mesenchymal transition through beta-catenin-T- cell factor-4-dependent expression of transforming growth factor-beta3.Mol. Biol. Cell200819114875488710.1091/mbc.e08‑05‑050618799618
    [Google Scholar]
  144. BeckerA. ThakurB.K. WeissJ.M. KimH.S. PeinadoH. LydenD. Extracellular vesicles in cancer: Cell-to- cell mediators of metastasis.Cancer Cell201630683684810.1016/j.ccell.2016.10.00927960084
    [Google Scholar]
  145. DedierM. MagneB. NivetM. BanzetS. TrouillasM. Anti-inflammatory effect of interleukin-6 highly enriched in secretome of two clinically relevant sources of mesenchymal stromal cells.Front. Cell Dev. Biol.202311124412010.3389/fcell.2023.124412037745306
    [Google Scholar]
  146. Janowska-WieczorekA. WysoczynskiM. KijowskiJ. Marquez-CurtisL. MachalinskiB. RatajczakJ. RatajczakM.Z. Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer.Int. J. Cancer2005113575276010.1002/ijc.2065715499615
    [Google Scholar]
  147. FerlizzaE. RomanielloD. BorrelliF. PaganoF. GironeC. GelfoV. KuhreR.S. MorselliA. MazzeschiM. SgarziM. FilippiniD.M. D’UvaG. LauriolaM. Extracellular vesicles and epidermal growth factor receptor activation: Interplay of drivers in cancer progression.Cancers20231511297010.3390/cancers1511297037296932
    [Google Scholar]
  148. XuY. FengK. ZhaoH. DiL. WangL. WangR. Tumor-derived extracellular vesicles as messengers of natural products in cancer treatment.Theranostics20221241683171410.7150/thno.6777535198064
    [Google Scholar]
  149. ZhouX. YanT. HuangC. XuZ. WangL. JiangE. WangH. ChenY. LiuK. ShaoZ. ShangZ. Melanoma cell-secreted exosomal miR-155-5p induce proangiogenic switch of cancer-associated fibroblasts via SOCS1/JAK2/STAT3 signaling pathway.J. Exp. Clin. Cancer Res.201837124210.1186/s13046‑018‑0911‑330285793
    [Google Scholar]
  150. CaiL. ZhangQ. DuL. ZhengF. Silencing of miR-1246 induces cell cycle arrest and apoptosis in cisplatin-resistant ovarian cancer cells by promoting ZNF23 transcription.Cytogenet. Genome Res.202116110-1148850010.1159/00052006934923485
    [Google Scholar]
  151. WuL. ZhangX. ZhangB. ShiH. YuanX. SunY. PanZ. QianH. XuW. Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.Tumour Biol.2016379121691218010.1007/s13277‑016‑5071‑527220495
    [Google Scholar]
  152. ArkhypovI. LasserS. PetrovaV. WeberR. GrothC. UtikalJ. AltevogtP. UmanskyV. Myeloid cell modulation by tumor-derived extracellular vesicles.Int. J. Mol. Sci.20202117631910.3390/ijms2117631932878277
    [Google Scholar]
  153. RoefsM.T. SluijterJ.P.G. VaderP. Extracellular vesicle-associated proteins in tissue repair.Trends Cell Biol.20203012990101310.1016/j.tcb.2020.09.00933069512
    [Google Scholar]
  154. GuoP. HuB. GuW. XuL. WangD. HuangH.J.S. CaveneeW.K. ChengS.Y. Platelet-derived growth factor-B enhances glioma angiogenesis by stimulating vascular endothelial growth factor expression in tumor endothelia and by promoting pericyte recruitment.Am. J. Pathol.200316241083109310.1016/S0002‑9440(10)63905‑312651601
    [Google Scholar]
  155. KimH. LeeS. ShinE. SeongK.M. JinY.W. YounH. YounB. The emerging roles of exosomes as EMT regulators in cancer.Cells20209486110.3390/cells904086132252322
    [Google Scholar]
  156. WangJ. ZhangC. LiC. ZhaoD. LiS. MaL. CuiY. WeiX. ZhaoY. GaoY. MicroRNA-92a promotes vascular smooth muscle cell proliferation and migration through the ROCK/MLCK signalling pathway.J. Cell. Mol. Med.20192353696371010.1111/jcmm.1427430907506
    [Google Scholar]
  157. WuM. WangM. JiaH. WuP. Extracellular vesicles: Emerging anti-cancer drugs and advanced functionalization platforms for cancer therapy.Drug Deliv.20222912513253810.1080/10717544.2022.210440435915054
    [Google Scholar]
  158. KimM.S. HaneyM.J. ZhaoY. MahajanV. DeygenI. KlyachkoN.L. InskoeE. PiroyanA. SokolskyM. OkolieO. HingtgenS.D. KabanovA.V. BatrakovaE.V. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells.Nanomedicine201612365566410.1016/j.nano.2015.10.01226586551
    [Google Scholar]
  159. TrajkovicK. HsuC. ChiantiaS. RajendranL. WenzelD. WielandF. SchwilleP. BrüggerB. SimonsM. Ceramide triggers budding of exosome vesicles into multivesicular endosomes.Science200831958671244124710.1126/science.115312418309083
    [Google Scholar]
  160. ZwickeG.L. Ali MansooriG. JefferyC.J. Utilizing the folate receptor for active targeting of cancer nanotherapeutics.Nano Rev.2012311849610.3402/nano.v3i0.1849623240070
    [Google Scholar]
  161. Fernández-MessinaL. Rodríguez-GalánA. de YébenesV.G. Gutiérrez-VázquezC. TenreiroS. SeabraM.C. RamiroA.R. Sánchez-MadridF. Transfer of extracellular vesicle-micro RNA controls germinal center reaction and antibody production.EMBO Rep.2020214e4892510.15252/embr.20194892532073750
    [Google Scholar]
  162. YimK.H.W. Al HroutA. BorgoniS. ChahwanR. Extracellular vesicles orchestrate immune and tumor interaction networks.Cancers20201212369610.3390/cancers1212369633317058
    [Google Scholar]
  163. WojtukiewiczM.Z. RekM.M. KarpowiczK. GórskaM. PolityńskaB. WojtukiewiczA.M. MoniuszkoM. RadziwonP. TuckerS.C. HonnK.V. Inhibitors of immune checkpoints-PD-1, PD-L1, CTLA-4-new opportunities for cancer patients and a new challenge for internists and general practitioners.Cancer Metastasis Rev.202140394998210.1007/s10555‑021‑09976‑034236546
    [Google Scholar]
  164. BuchbinderE.I. DesaiA. CTLA-4 and PD-1 pathways.Am. J. Clin. Oncol.20163919810610.1097/COC.000000000000023926558876
    [Google Scholar]
  165. WhitesideT.L. Exosomes and tumor-mediated immune suppression.J. Clin. Invest.201612641216122310.1172/JCI8113626927673
    [Google Scholar]
  166. RobbinsP.D. MorelliA.E. Regulation of immune responses by extracellular vesicles.Nat. Rev. Immunol.201414319520810.1038/nri362224566916
    [Google Scholar]
  167. JiaoS. XiaW. YamaguchiH. WeiY. ChenM.K. HsuJ.M. HsuJ.L. YuW.H. DuY. LeeH.H. LiC.W. ChouC.K. LimS.O. ChangS.S. LittonJ. ArunB. HortobagyiG.N. HungM.C. PARP inhibitor upregulates PD-L1 expression and enhances cancer-associated immunosuppression.Clin. Cancer Res.201723143711372010.1158/1078‑0432.CCR‑16‑321528167507
    [Google Scholar]
  168. ChenY. WangL. ZhengM. ZhuC. WangG. XiaY. BlumenthalE.J. MaoW. WanY. Engineered extracellular vesicles for concurrent Anti-PDL1 immunotherapy and chemotherapy.Bioact. Mater.2022925126510.1016/j.bioactmat.2021.07.01234820569
    [Google Scholar]
  169. GiustiI. FrancescoM.D. AscenzoS.D. PalmeriniM.G. MacchiarelliG. CartaG. DoloV. Ovarian cancer-derived extracellular vesicles affect normal human fibroblast behavior.Cancer Biol. Ther.201819814410.1080/15384047.2018.145128629580188
    [Google Scholar]
  170. MoY. LeungL.L. MakC.S.L. WangX. ChanW.S. HuiL.M.N. TangH.W.M. SiuM.K.Y. SharmaR. XuD. TsuiS.K.W. NganH.Y.S. YungM.M.H. ChanK.K.L. ChanD.W. Tumor-secreted exosomal miR-141 activates tumor-stroma interactions and controls premetastatic niche formation in ovarian cancer metastasis.Mol. Cancer2023221410.1186/s12943‑022‑01703‑936624516
    [Google Scholar]
  171. CheaibB. AugusteA. LearyA. The PI3K/Akt/mTOR pathway in ovarian cancer: Therapeutic opportunities and challenges.Chin. J. Cancer201534141610.5732/cjc.014.1028925556614
    [Google Scholar]
  172. TianW. LeiN. ZhouJ. ChenM. GuoR. QinB. LiY. ChangL. Extracellular vesicles in ovarian cancer chemoresistance, metastasis, and immune evasion.Cell Death Dis.20221316410.1038/s41419‑022‑04510‑835042862
    [Google Scholar]
  173. LemmonM.A. SchlessingerJ. Cell signaling by receptor tyrosine kinases.Cell201014171117113410.1016/j.cell.2010.06.01120602996
    [Google Scholar]
  174. GhoneumA. SaidN. PI3K-AKT-mTOR and NFκB pathways in ovarian cancer: Implications for targeted therapeutics.Cancers201911794910.3390/cancers1107094931284467
    [Google Scholar]
  175. SteelmanL.S. ChappellW.H. AbramsS.L. KempfC.R. LongJ. LaidlerP. MijatovicS. Maksimovic-IvanicD. StivalaF. MazzarinoM.C. DoniaM. FagoneP. MalaponteG. NicolettiF. LibraM. MilellaM. TafuriA. BonatiA. BäseckeJ. CoccoL. EvangelistiC. MartelliA.M. MontaltoG. CervelloM. McCubreyJ.A. Roles of the Raf/MEK/ERK and PI3K/PTEN/Akt/mTOR pathways in controlling growth and sensitivity to therapy-implications for cancer and aging.Aging20113319222210.18632/aging.10029621422497
    [Google Scholar]
  176. PolchiA. MaginiA. MeoD.D. TanciniB. EmilianiC. mTOR signaling and neural stem cells: The tuberous sclerosis complex model.Int. J. Mol. Sci.2018195147410.3390/ijms1905147429772672
    [Google Scholar]
  177. RomagnoliA. MaracciC. D’AgostinoM. La TeanaA. Di MarinoD. Targeting mTOR and eIF4E: A feasible scenario in ovarian cancer therapy.Cancer Drug Resist.20214359660610.20517/cdr.2021.2035582305
    [Google Scholar]
  178. RozengurtE. SoaresH.P. Sinnet-SmithJ. Suppression of feedback loops mediated by PI3K/mTOR induces multiple overactivation of compensatory pathways: An unintended consequence leading to drug resistance.Mol. Cancer Ther.201413112477248810.1158/1535‑7163.MCT‑14‑033025323681
    [Google Scholar]
  179. XieY. LeiX. ZhaoG. GuoR. CuiN. mTOR in programmed cell death and its therapeutic implications.Cytokine Growth Factor Rev.202371-72668110.1016/j.cytogfr.2023.06.00237380596
    [Google Scholar]
  180. MagawayC. KimE. JacintoE. Targeting mTOR and metabolism in cancer: Lessons and innovations.Cells2019812158410.3390/cells812158431817676
    [Google Scholar]
  181. RinneN. ChristieE.L. ArdashevaA. KwokC.H. DemchenkoN. LowC. Tralau-StewartC. FotopoulouC. CunneaP. Targeting the PI3K/AKT/mTOR pathway in epithelial ovarian cancer, therapeutic treatment options for platinum-resistant ovarian cancer.Cancer Drug Resist.20214357359510.20517/cdr.2021.0535582310
    [Google Scholar]
  182. HendrikseC.S.E. TheelenP.M.M. van der PloegP. WestgeestH.M. BoereI.A. ThijsA.M.J. OttevangerP.B. van de StolpeA. LambrechtsS. BekkersR.L.M. PiekJ.M.J. The potential of RAS/RAF/MEK/ERK (MAPK) signaling pathway inhibitors in ovarian cancer: A systematic review and meta-analysis.Gynecol. Oncol.2023171839410.1016/j.ygyno.2023.01.03836841040
    [Google Scholar]
  183. IqbalN. IqbalN. Human epidermal growth factor receptor 2 (HER2) in cancers: Overexpression and therapeutic implications.Mol. Biol. Int.201420141910.1155/2014/85274825276427
    [Google Scholar]
  184. WeiY. ErfaniS. SchweerD. de GouveaR. QadirJ. ShiJ. ChengK. WuD. CravenR. WuY. OlivierT. BaldwinL.A. ZhouB. ZhouY. ZhaoW. YangB.B. UelandF.R. YangX.H. Targeting receptor tyrosine kinases in ovarian cancer: Genomic dysregulation, clinical evaluation of inhibitors, and potential for combinatorial therapies.Mol. Ther. Oncolytics20232829330610.1016/j.omto.2023.02.00636911068
    [Google Scholar]
  185. MaruyamaI. Mechanisms of activation of receptor tyrosine kinases: Monomers or dimers.Cells20143230433010.3390/cells302030424758840
    [Google Scholar]
  186. VigilD. CherfilsJ. RossmanK.L. DerC.J. Ras superfamily GEFs and GAPs: Validated and tractable targets for cancer therapy?Nat. Rev. Cancer2010101284285710.1038/nrc296021102635
    [Google Scholar]
  187. TherachiyilL. AnandA. AzmiA. BhatA. KorashyH.M. UddinS. Role of RAS signaling in ovarian cancer.F1000 Res.202211125310.12688/f1000research.126337.136451660
    [Google Scholar]
  188. SantarpiaL. LippmanS.M. El-NaggarA.K. Targeting the MAPK–RAS–RAF signaling pathway in cancer therapy.Expert Opin. Ther. Targets201216110311910.1517/14728222.2011.64580522239440
    [Google Scholar]
  189. CargnelloM. RouxP.P. Activation and function of the MAPKs and their substrates, the MAPK-activated protein kinases.Microbiol. Mol. Biol. Rev.2011751508310.1128/MMBR.00031‑1021372320
    [Google Scholar]
  190. LakeD. CorrêaS.A.L. MüllerJ. Negative feedback regulation of the ERK1/2 MAPK pathway.Cell. Mol. Life Sci.201673234397441310.1007/s00018‑016‑2297‑827342992
    [Google Scholar]
  191. ZhouB. SunC. LiN. ShanW. LuH. GuoL. GuoE. XiaM. WengD. MengL. HuJ. MaD. ChenG. Cisplatin-induced CCL5 secretion from CAFs promotes cisplatin-resistance in ovarian cancer via regulation of the STAT3 and PI3K/Akt signaling pathways.Int. J. Oncol.20164852087209710.3892/ijo.2016.344226983899
    [Google Scholar]
  192. OkkenhaugK. GrauperaM. VanhaesebroeckB. Targeting PI3K in cancer: Impact on tumor cells, their protective stroma, angiogenesis, and immunotherapy.Cancer Discov.20166101090110510.1158/2159‑8290.CD‑16‑071627655435
    [Google Scholar]
  193. LimaB. AbreuM.H. SousaS. BartoschC. PereiraD. Impressive and durable clinical responses obtained with dabrafenib and trametinib in low-grade serous ovarian cancer harbouring a BRAF V600E mutation.Gynecol. Oncol. Rep.20224010094210.1016/j.gore.2022.10094235242981
    [Google Scholar]
  194. GershensonD.M. MillerA. BradyW.E. PaulJ. CartyK. RodgersW. MillanD. ColemanR.L. MooreK.N. BanerjeeS. ConnollyK. SecordA.A. O’MalleyD.M. DorigoO. GaillardS. GabraH. SlomovitzB. HanjaniP. FarleyJ. ChurchmanM. EwingA. HollisR.L. HerringtonC.S. HuangH.Q. WenzelL. GourleyC. Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): An international, randomised, open-label, multicentre, phase 2/3 trial.Lancet20223991032454155310.1016/S0140‑6736(21)02175‑935123694
    [Google Scholar]
  195. LawalB. LoW.C. MokgautsiN. SumitraM.R. KhedkarH. WuA.T. HuangH.S. A preclinical report of a cobimetinib-inspired novel anticancer small-molecule scaffold of isoflavones, NSC777213, for targeting PI3K/AKT/mTOR/MEK in multiple cancers.Am. J. Cancer Res.20211162590261734249417
    [Google Scholar]
  196. ZhuY. LiuY. LuoY. CaiM. ShenP. LiJ. ChenH. BaoW. Anti-angiogenic therapy in ovarian cancer: Current situation & prospects.Indian J. Med. Res.2021154568069010.4103/ijmr.IJMR_1160_1935532586
    [Google Scholar]
  197. ShibuyaM. Vascular endothelial growth factor (VEGF) and its receptor (VEGFR) signaling in angiogenesis: A crucial target for anti- and pro-angiogenic therapies.Genes Cancer20112121097110510.1177/194760191142303122866201
    [Google Scholar]
  198. ShibuyaM. Claesson-WelshL. Signal transduction by VEGF receptors in regulation of angiogenesis and lymphangiogenesis.Exp. Cell Res.2006312554956010.1016/j.yexcr.2005.11.01216336962
    [Google Scholar]
  199. KochS. Claesson-WelshL. Signal transduction by vascular endothelial growth factor receptors.Cold Spring Harb. Perspect. Med.201227a00650210.1101/cshperspect.a00650222762016
    [Google Scholar]
  200. WangX. BoveA.M. SimoneG. MaB. Molecular bases of VEGFR-2-mediated physiological function and pathological role.Front. Cell Dev. Biol.2020859928110.3389/fcell.2020.59928133304904
    [Google Scholar]
  201. Masoumi MoghaddamS. AminiA. MorrisD.L. PourgholamiM.H. Significance of vascular endothelial growth factor in growth and peritoneal dissemination of ovarian cancer.Cancer Metastasis Rev.2012311-214316210.1007/s10555‑011‑9337‑522101807
    [Google Scholar]
  202. TrifanescuO.G. GalesL.N. TanaseB.C. MarinescuS.A. TrifanescuR.A. GruiaI.M. PaunM.A. RebegeaL. MitricaR. SerbanescuL. Prognostic role of vascular endothelial growth factor and correlation with oxidative stress markers in locally advanced and metastatic ovarian cancer patients.Diagnostics2023131166
    [Google Scholar]
  203. SpannuthW.A. NickA.M. JenningsN.B. Armaiz-PenaG.N. MangalaL.S. DanesC.G. LinY.G. MerrittW.M. ThakerP.H. KamatA.A. HanL.Y. TonraJ.R. ColemanR.L. EllisL.M. SoodA.K. Functional significance of VEGFR-2 on ovarian cancer cells.Int. J. Cancer200912451045105310.1002/ijc.2402819058181
    [Google Scholar]
  204. ChoiH.J. Armaiz PenaG.N. PradeepS. ChoM.S. ColemanR.L. SoodA.K. Anti-vascular therapies in ovarian cancer: Moving beyond anti-VEGF approaches.Cancer Metastasis Rev.2015341194010.1007/s10555‑014‑9538‑925544368
    [Google Scholar]
  205. MurphyA.D. MorganR.D. ClampA.R. JaysonG.C. The role of vascular endothelial growth factor inhibitors in the treatment of epithelial ovarian cancer.Br. J. Cancer2022126685186410.1038/s41416‑021‑01605‑534716396
    [Google Scholar]
  206. GarciaA. SinghH. Bevacizumab and ovarian cancer.Ther. Adv. Med. Oncol.20135213314110.1177/175883401246766123450196
    [Google Scholar]
  207. MaoC.L. SeowK.M. ChenK.H. The utilization of bevacizumab in patients with advanced ovarian cancer: A systematic review of the mechanisms and effects.Int. J. Mol. Sci.20222313691110.3390/ijms2313691135805914
    [Google Scholar]
  208. PerrenT.J. SwartA.M. PfistererJ. LedermannJ.A. Pujade-LauraineE. KristensenG. CareyM.S. BealeP. CervantesA. KurzederC. BoisA. SehouliJ. KimmigR. StähleA. CollinsonF. EssapenS. GourleyC. LortholaryA. SelleF. MirzaM.R. LeminenA. PlanteM. StarkD. QianW. ParmarM.K.B. OzaA.M. ICON7 Investigators A phase 3 trial of bevacizumab in ovarian cancer.N. Engl. J. Med.2011365262484249610.1056/NEJMoa110379922204725
    [Google Scholar]
  209. FrumanD.A. ChiuH. HopkinsB.D. BagrodiaS. CantleyL.C. AbrahamR.T. The PI3K pathway in human disease.Cell2017170460563510.1016/j.cell.2017.07.02928802037
    [Google Scholar]
  210. RahmanM. NakayamaK. RahmanM.T. NakayamaN. IshikawaM. KatagiriA. IidaK. NakayamaS. OtsukiY. ShihI.M. MiyazakiK. Clinicopathologic and biological analysis of PIK3CA mutation in ovarian clear cell carcinoma.Hum. Pathol.201243122197220610.1016/j.humpath.2012.03.01122705003
    [Google Scholar]
  211. AbeA. MinaguchiT. OchiH. OnukiM. OkadaS. MatsumotoK. SatohT. OkiA. YoshikawaH. PIK3CA overexpression is a possible prognostic factor for favorable survival in ovarian clear cell carcinoma.Hum. Pathol.201344219920710.1016/j.humpath.2012.05.00522955107
    [Google Scholar]
  212. YamamotoS. TsudaH. TakanoM. IwayaK. TamaiS. MatsubaraO. PIK3CA mutation is an early event in the development of endometriosis-associated ovarian clear cell adenocarcinoma.J. Pathol.2011225218919410.1002/path.294021735444
    [Google Scholar]
  213. YeS. YangJ. YouY. CaoD. HuangH. WuM. ChenJ. LangJ. ShenK. Clinicopathologic significance of HNF-1β, AIRD1A, and PIK3CA expression in ovarian clear cell carcinoma.Medicine2016959e300310.1097/MD.000000000000300326945423
    [Google Scholar]
  214. LiS.Y. RongM. GrieuF. IacopettaB. PIK3CA mutations in breast cancer are associated with poor outcome.Breast Cancer Res. Treat.2006961919510.1007/s10549‑005‑9048‑016317585
    [Google Scholar]
  215. ItamochiH. OishiT. OumiN. TakeuchiS. YoshiharaK. MikamiM. YaegashiN. TeraoY. TakeharaK. UshijimaK. WatariH. AokiD. KimuraT. NakamuraT. YokoyamaY. KigawaJ. SugiyamaT. Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma.Br. J. Cancer2017117571772410.1038/bjc.2017.22828728166
    [Google Scholar]
  216. WuY.H. HuangY.F. ChenC.C. HuangC.Y. ChouC.Y. Comparing PI3K/Akt inhibitors used in ovarian cancer treatment.Front. Pharmacol.20201120610.3389/fphar.2020.0020632194423
    [Google Scholar]
  217. DengJ. BaiX. FengX. NiJ. BeretovJ. GrahamP. LiY. Inhibition of PI3K/Akt/mTOR signaling pathway alleviates ovarian cancer chemoresistance through reversing epithelial-mesenchymal transition and decreasing cancer stem cell marker expression.BMC Cancer201919161810.1186/s12885‑019‑5824‑931234823
    [Google Scholar]
  218. JuricD. RodonJ. TaberneroJ. JankuF. BurrisH.A. SchellensJ.H.M. MiddletonM.R. BerlinJ. SchulerM. Gil-MartinM. RugoH.S. Seggewiss-BernhardtR. HuangA. BootleD. DemanseD. BlumensteinL. CoughlinC. QuadtC. BaselgaJ. Phosphatidylinositol 3-kinase α–selective inhibition with alpelisib (BYL719) in PIK3CA -altered solid tumors: Results from the first-in-human study.J. Clin. Oncol.201836131291129910.1200/JCO.2017.72.710729401002
    [Google Scholar]
  219. SohnE.J. PIK3R3, a regulatory subunit of PI3K, modulates ovarian cancer stem cells and ovarian cancer development and progression by integrative analysis.BMC Cancer202222170810.1186/s12885‑022‑09807‑735761259
    [Google Scholar]
  220. CamblinA.J. TanG. CurleyM.D. YannatosI. IadevaiaS. RimkunasV. Mino-KenudsonM. BloomT. SchoeberlB. DrummondD.C. LugovskoyA.A. LouisC.U. AskoxylakisV. Dual targeting of IGF-1R and ErbB3 as a potential therapeutic regimen for ovarian cancer.Sci. Rep.2019911683210.1038/s41598‑019‑53322‑y31728045
    [Google Scholar]
  221. SongJ.H. PadiS.K.R. LuevanoL.A. MindenM.D. DeAngeloD.J. HardimanG. BallL.E. WarfelN.A. KraftA.S. Insulin receptor substrate 1 is a substrate of the Pim protein kinases.Oncotarget2016715201522016510.18632/oncotarget.791826956053
    [Google Scholar]
  222. DariciS. AlkhaldiH. HorneG. JørgensenH.G. MarmiroliS. HuangX. Targeting PI3K/Akt/mTOR in AML: Rationale and clinical evidence.J. Clin. Med.202099293410.3390/jcm909293432932888
    [Google Scholar]
  223. XuD. CobbM.G. GavilanoL. WitherspoonS.M. WilliamsD. WhiteC.D. TavernaP. BednarskiB.K. KimH.J. BaldwinA.S. BainesA.T. Inhibition of oncogenic Pim-3 kinase modulates transformed growth and chemosensitizes pancreatic cancer cells to gemcitabine.Cancer Biol. Ther.201314649250110.4161/cbt.2434323760491
    [Google Scholar]
  224. HanrahanA.J. SchultzN. WestfalM.L. SakrR.A. GiriD.D. ScarperiS. JanikarimanM. OlveraN. StevensE.V. SheQ.B. AghajanianC. KingT.A. de StanchinaE. SpriggsD.R. HeguyA. TaylorB.S. SanderC. RosenN. LevineD.A. SolitD.B. Genomic complexity and AKT dependence in serous ovarian cancer.Cancer Discov.201221566710.1158/2159‑8290.CD‑11‑017022328975
    [Google Scholar]
  225. XuS. FuG.B. TaoZ. OuYangJ. KongF. JiangB.H. WanX. ChenK. MiR-497 decreases cisplatin resistance in ovarian cancer cells by targeting mTOR/P70S6K1.Oncotarget2015628264572647110.18632/oncotarget.476226238185
    [Google Scholar]
  226. WangQ. TangY. YuH. YinQ. LiM. ShiL. ZhangW. LiD. LiL. CCL18 from tumor-cells promotes epithelial ovarian cancer metastasis via mTOR signaling pathway.Mol. Carcinog.201655111688169910.1002/mc.2241926457987
    [Google Scholar]
  227. ChenY. León-LetelierR.A. Abdel SaterA.H. VykoukalJ. DennisonJ.B. HanashS. FahrmannJ.F. c-MYC-driven polyamine metabolism in ovarian cancer: From pathogenesis to early detection and therapy.Cancers202315362310.3390/cancers1503062336765581
    [Google Scholar]
  228. WhillockA.L. MambetsarievN. LinW.W. StunzL.L. BishopG.A. TRAF3 regulates the oncogenic proteins Pim2 and c-Myc to restrain survival in normal and malignant B cells.Sci. Rep.2019911288410.1038/s41598‑019‑49390‑931501481
    [Google Scholar]
/content/journals/cmc/10.2174/0109298673331849240930140120
Loading
/content/journals/cmc/10.2174/0109298673331849240930140120
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test