【《卵巢癌的研究进展文献综述》1900字】

卵巢癌的研究进展文献综述1.1卵巢癌的发病机制有很多因素可以增加卵巢癌的患病风险，例如遗传因素、高龄、绝经后雌雄激素治疗的使用、环境和生活因素、不孕症和未生育ADDINEN.CITEADDINEN.CITE.DATA[11]。遗传因素中特别是基因突变在卵巢癌的发病机制中扮演了十分重要的角色。目前，卵巢癌中研究最深入的基因突变是与DNA修复有关的基因突变,常见的遗传基因有BRCA1、BRCA2和BRIP1ADDINEN.CITEADDINEN.CITE.DATA[12]，BRCA1和BRCA2携带者的卵巢癌发病率随着年龄的增长而增加ADDINEN.CITEADDINEN.CITE.DATA增加增加[13]。卵巢癌中另一个常见基因突变是TP53，TP53是高级别浆液性卵巢癌(High-GradeSerousOvarianCarcer，HGSOC)中最常见的突变基因ADDINEN.CITE<EndNote><Cite><Author>Kurman</Author><Year>2013</Year><RecNum>767</RecNum><DisplayText><styleface="superscript">[14]</style></DisplayText><record><rec-number>767</rec-number><foreign-keys><keyapp="EN"db-id="9sdeda2f70fw5detxd1p2dvor2vw2aeweape"timestamp="1611659907"guid="ffdd044a-360d-40ab-9b78-a7d04cb7820a">767</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Kurman,R.J.</author></authors></contributors><auth-address>DepartmentofGynecology.</auth-address><titles><title>Originandmolecularpathogenesisofovarianhigh-gradeserouscarcinoma</title><secondary-title>AnnOncol</secondary-title><alt-title>Annalsofoncology:officialjournaloftheEuropeanSocietyforMedicalOncology</alt-title></titles><periodical><full-title>AnnOncol</full-title><abbr-1>Annalsofoncology:officialjournaloftheEuropeanSocietyforMedicalOncology</abbr-1></periodical><alt-periodical><full-title>AnnOncol</full-title><abbr-1>Annalsofoncology:officialjournaloftheEuropeanSocietyforMedicalOncology</abbr-1></alt-periodical><pages>x16-21</pages><volume>24Suppl10</volume><edition>2013/12/07</edition><keywords><keyword>Carcinoma/classification/*epidemiology/*genetics/pathology</keyword><keyword>ClinicalTrialsasTopic</keyword><keyword>Female</keyword><keyword>Humans</keyword><keyword>NeoplasmGrading</keyword><keyword>OvarianNeoplasms/classification/*epidemiology/*genetics/pathology</keyword><keyword>QualityofLife</keyword><keyword>TreatmentOutcome</keyword></keywords><dates><year>2013</year><pub-dates><date>Dec</date></pub-dates></dates><isbn>0923-7534</isbn><accession-num>24265397</accession-num><urls></urls><electronic-resource-num>10.1093/annonc/mdt463</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[14]。卵巢癌发病机制研究中的另一个热点领域是肿瘤免疫微环境的作用ADDINEN.CITEADDINEN.CITE.DATA[15]。卵巢恶性发展包括原发肿瘤的生长、治疗耐药和远处转移，这些并不仅仅取决于卵巢癌细胞的基因改变，还在很大程度上取决于卵巢癌发展所涉及的肿瘤细胞与肿瘤免疫微环境的共同作用ADDINEN.CITEADDINEN.CITE.DATA[15]。有研究表明，卵巢癌中细胞毒性T细胞浸润与总生存期（OverallSurvival，OS）的改善相关ADDINEN.CITEADDINEN.CITE.DATA[16]。例如，由肿瘤效应T细胞和肿瘤特异性抗体组成的抗肿瘤免疫反应可在卵巢癌患者的外周血、卵巢癌组织和腹水中检测到ADDINEN.CITE<EndNote><Cite><Author>Zsiros</Author><Year>2014</Year><RecNum>775</RecNum><DisplayText><styleface="superscript">[17]</style></DisplayText><record><rec-number>775</rec-number><foreign-keys><keyapp="EN"db-id="9sdeda2f70fw5detxd1p2dvor2vw2aeweape"timestamp="1611668326"guid="04a53b0e-d82f-47bf-8bad-3de43b46cc60">775</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Zsiros,E.</author><author>Tanyi,J.</author><author>Balint,K.</author><author>Kandalaft,L.E.</author></authors></contributors><auth-address>aOvarianCancerResearchCenter,SmilowTranslationalResearchCenter,PerelmanSchoolofMedicineofUniversityofPennsylvaniaPhiladelphia,Pennsylvania,USAbDepartmentofOncology,LudwigCancerCenter,CentreHospitalierUniversitaireVaudois,Lausanne,Switzerland.</auth-address><titles><title>Immunotherapyforovariancancer:recentadvancesandperspectives</title><secondary-title>CurrOpinOncol</secondary-title><alt-title>Currentopinioninoncology</alt-title></titles><periodical><full-title>CurrOpinOncol</full-title><abbr-1>Currentopinioninoncology</abbr-1></periodical><alt-periodical><full-title>CurrOpinOncol</full-title><abbr-1>Currentopinioninoncology</abbr-1></alt-periodical><pages>492-500</pages><volume>26</volume><number>5</number><edition>2014/07/19</edition><keywords><keyword>Female</keyword><keyword>Humans</keyword><keyword>*Immunotherapy</keyword><keyword>OvarianNeoplasms/drugtherapy/*immunology/radiotherapy/*therapy</keyword></keywords><dates><year>2014</year><pub-dates><date>Sep</date></pub-dates></dates><isbn>1040-8746</isbn><accession-num>25036883</accession-num><urls></urls><electronic-resource-num>10.1097/cco.0000000000000111</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[17]。在肿瘤微环境中促血管生成因子能够促进肿瘤的生长和转移，在卵巢癌的发生发展中起着关键作用ADDINEN.CITEADDINEN.CITE.DATA[18]。卵巢癌最有效的促血管生成因子是血管内皮生长因子(VascularEndothelialGrowthFactor,VEGF)，其他促血管生成因子在卵巢癌中也有被发现，例如成纤维细胞生长因子、血管生成素、内皮素、IL-6、IL-8、巨噬细胞趋化蛋白和血小板衍生生长因子等ADDINEN.CITEADDINEN.CITE.DATA[19,20]。综上所述，卵巢癌的发病机制是非常复杂的，现有发病机制仍有许多值得深入探究的方向。1.2卵巢癌的治疗进展当前卵巢癌的标准治疗方式是最大限度的肿瘤细胞减灭术及术后以顺铂和紫杉醇为主的联合化疗方案。对于早期卵巢癌患者，临床一般采用全面分期手术，对于晚期卵巢癌患者的手术则强调满意的初次肿瘤细胞减灭术或中间型肿瘤细胞减灭术ADDINEN.CITE<EndNote><Cite><Author>Makar</Author><Year>2016</Year><RecNum>695</RecNum><DisplayText><styleface="superscript">[21]</style></DisplayText><record><rec-number>695</rec-number><foreign-keys><keyapp="EN"db-id="9sdeda2f70fw5detxd1p2dvor2vw2aeweape"timestamp="1611299544"guid="bc7663ae-a1eb-42e5-bd40-743325573acf">695</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Makar,AminP.</author><author>Tropé,ClaesG.</author><author>Tummers,Philippe</author><author>Denys,Hannelore</author><author>Vandecasteele,Katrien</author></authors></contributors><titles><title>AdvancedOvarianCancer:PrimaryorIntervalDebulking?FiveCategoriesofPatientsinViewoftheResultsofRandomizedTrialsandTumorBiology:PrimaryDebulkingSurgeryandIntervalDebulkingSurgeryforAdvancedOvarianCancer</title><secondary-title>TheOncologist</secondary-title></titles><periodical><full-title>TheOncologist</full-title></periodical><pages>745-754</pages><volume>21</volume><number>6</number><dates><year>2016</year></dates><publisher>Wiley</publisher><isbn>1083-7159</isbn><urls><related-urls><url>/10.1634/theoncologist.2015-0239</url></related-urls><pdf-urls><url>file://C:\Users\sanmi\Downloads\endnote_click\Makar-2016-Advanced-ovarian-cancer-primary-or-.pdf</url></pdf-urls></urls><electronic-resource-num>10.1634/theoncologist.2015-0239</electronic-resource-num></record></Cite></EndNote>[21]。目前的化疗方式主要包括包括静脉化疗、腹腔热灌注化疗（HyperthermicIntraperitonealChemotherapy，HIPEC）等。HIPEC近年来在卵巢癌治疗中的有益作用不断显现，已经证明能够明显改善卵巢癌患者无进展生存期（ProgressionFreeSurvive，PFS）和OSADDINEN.CITE<EndNote><Cite><Author>VanDriel</Author><Year>2018</Year><RecNum>701</RecNum><DisplayText><styleface="superscript">[22]</style></DisplayText><record><rec-number>701</rec-number><foreign-keys><keyapp="EN"db-id="9sdeda2f70fw5detxd1p2dvor2vw2aeweape"timestamp="1611319767"guid="6935c241-deec-48aa-93d2-1ef68926d1e8">701</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>VanDriel,WillemienJ.</author><author>Koole,SimoneN.</author><author>Sikorska,Karolina</author><author>SchagenVanLeeuwen,JulesH.</author><author>Schreuder,HenkW.R.</author><author>Hermans,RalphH.M.</author><author>DeHingh,IgnaceH.J.T.</author><author>VanDerVelden,Jacobus</author><author>Arts,HenriëtteJ.</author><author>Massuger,LeonF.A.G.</author><author>Aalbers,ArendG.J.</author><author>Verwaal,VictorJ.</author><author>Kieffer,JacobienM.</author><author>VanDeVijver,KoenK.</author><author>VanTinteren,Harm</author><author>Aaronson,NeilK.</author><author>Sonke,GabeS.</author></authors></contributors><titles><title>HyperthermicIntraperitonealChemotherapyinOvarianCancer</title><secondary-title>NewEnglandJournalofMedicine</secondary-title></titles><periodical><full-title>NewEnglandJournalofMedicine</full-title></periodical><pages>230-240</pages><volume>378</volume><number>3</number><dates><year>2018</year></dates><publisher>MassachusettsMedicalSociety</publisher><isbn>0028-4793</isbn><urls><related-urls><url>/10.1056/nejmoa1708618</url></related-urls><pdf-urls><url>file://C:\Users\sanmi\Downloads\endnote_click\Van-driel-2018-Hyperthermic-intraperitoneal-chemot(2).pdf</url></pdf-urls></urls><electronic-resource-num>10.1056/nejmoa1708618</electronic-resource-num></record></Cite></EndNote>[22]。有研究表明，新辅助化疗对于大多数IV期卵巢癌患者来说，是其标准治疗ADDINEN.CITEADDINEN.CITE.DATA[23]。然而，化疗耐药是卵巢癌治疗的新难题，开发针对卵巢癌耐药治疗的新方案成为今后研究的重要任务。近年来，靶向治疗逐渐改变了卵巢癌的治疗现状。目前临床应用效果最好的靶向药物为聚腺苷二磷酸核糖聚合酶（PolyADP-RibosePolymerase，PARP）抑制剂ADDINEN.CITEADDINEN.CITE.DATA[24]，已经有三种不同的PARP抑制剂被批准用于铂敏感复发性卵巢癌患者的维持治疗（尼拉帕尼、奥拉帕尼和瑞卡帕布）ADDINEN.CITEADDINEN.CITE.DATA[25]，其中奥拉帕尼是唯一批准用于原发性BRCA突变晚期高级别卵巢癌患者的一线维持治疗方案ADDINEN.CITEADDINEN.CITE.DATA[26]。而抗VEGF体中的贝伐单抗也已被证明能够改善卵巢癌患者的PFS，其在疾病进展风险高的人群中受益更大ADDINEN.CITEADDINEN.CITE.DATA[27]。目前一些新的治疗方法正在研究中，为卵巢癌的治疗带来了新的曙光。利用嵌合抗原受体T细胞（ChimericAntigenReceptorTcells，CAR-Tcells）是一种潜在的对抗转移性卵巢癌的新方向，它在杀死恶性肿瘤细胞方面突显出优势，在实体肿瘤如卵巢癌中也表现出重要的潜在应用价值ADDINEN.CITEADDINEN.CITE.DATA[28]。根据权威研究，在小鼠卵巢癌模型中，将载有活化CAR-Tcells的镍钛诺薄膜直接递送至肿瘤细胞，可促进T细胞的快速扩增，并显著改善了小鼠的存活率ADDINEN.CITEADDINEN.CITE.DATA[29]。尽管对于CAR-Tcells的研究取得了进展，但利用CAR-Tcells治疗卵巢癌仍处于起步阶段。此外，疫苗疗法的出现也给卵巢癌的治疗带来了新的希望。有研究显示，使用氧化的全肿瘤裂解液树突状细胞(DendriticCell,DC)疫苗在诱导广泛的抗肿瘤免疫方面是安全和有效的ADDINEN.CITEADDINEN.CITE.DATA[30]，不过目前缺乏更进一步的临床证据。同时，有研究发现几乎所有肿瘤细胞都过度表达CD47，从而使癌症细胞能够逃避巨噬细胞和其他吞噬细胞的免疫监视。因此，对于所有表达CD47的肿瘤细胞来说，抑制CD47的表达是一个很有吸引力的治疗方向ADDINEN.CITE[31]。在一项Ib期临床试验中证实了CD47抑制剂5F9联合利妥昔单抗在非霍奇金淋巴瘤患者中是安全的，能够诱导持久地完全缓解ADDINEN.CITEADDINEN.CITE.DATA[32]，或许在将来能够据此研发出一种卵巢癌新疗法来改善卵巢癌患者预后。参考文献1.SiegelRL,MillerKD,JemalA.Cancerstatistics,2020.CACancerJClin,2020,70(1):7-30.2.YaoSE,TripconyL,SandayK,RobertsonJ,PerrinL,ChettyN,LandR,GarrettA,ObermairA,NascimentoM,TangA,JagasiaN,SinghP,NicklinJ.Survivaloutcomesafterdelayedcytoreductionsurgeryfollowingneoadjuvantchemotherapyinadvancedepithelialovariancancer.IntJGynecolCancer,2020,30(12):1935-1942.3.Gato-CañasM,ZuazoM,ArasanzH,Ibañez-VeaM,LorenzoL,Fernandez-HinojalG,VeraR,SmerdouC,MartisovaE,ArozarenaI,WellbrockC,LlopizD,RuizM,SarobeP,BreckpotK,KochanG,EscorsD.PDL1SignalsthroughConservedSequenceMotifstoOvercomeInterferon-MediatedCytotoxicity.CellRep,2017,20(8):1818-1829.4.HamanishiJ,MandaiM,IwasakiM,OkazakiT,TanakaY,YamaguchiK,HiguchiT,YagiH,TakakuraK,MinatoN,HonjoT,FujiiS.Programmedcelldeath1ligand1and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