{"title":"内源性逆转录因子在癌症发展和治疗中的再激活","authors":"Charles A. Ishak, D. D. Carvalho","doi":"10.1146/annurev-cancerbio-030419-033525","DOIUrl":null,"url":null,"abstract":"Domesticated retroelements contribute extensively as regulatory elements within host gene networks. Upon germline integration, retroelement mobilization is restricted through epigenetic silencing, mutational degradation, and innate immune defenses described as the viral mimicry response. Recent discoveries reveal how early events in tumorigenesis reactivate retroelements to facilitate onco-exaptation, replication stress, retrotransposition, mitotic errors, and sterile inflammation, which collectively disrupt genome integrity. The characterization of altered epigenetic homeostasis at retroelements in cancer cells also reveals new epigenetic targets whose inactivation can bolster responses to cancer therapies. Recent discoveries reviewed here frame reactivated retroelements as both drivers of tumorigenesis and therapy responses, where their reactivation by emerging epigenetic therapies can potentiate immune checkpoint blockade, cancer vaccines, and other standard therapies.","PeriodicalId":54233,"journal":{"name":"Annual Review of Cancer Biology-Series","volume":" ","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2020-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1146/annurev-cancerbio-030419-033525","citationCount":"34","resultStr":"{\"title\":\"Reactivation of Endogenous Retroelements in Cancer Development and Therapy\",\"authors\":\"Charles A. Ishak, D. D. Carvalho\",\"doi\":\"10.1146/annurev-cancerbio-030419-033525\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Domesticated retroelements contribute extensively as regulatory elements within host gene networks. Upon germline integration, retroelement mobilization is restricted through epigenetic silencing, mutational degradation, and innate immune defenses described as the viral mimicry response. Recent discoveries reveal how early events in tumorigenesis reactivate retroelements to facilitate onco-exaptation, replication stress, retrotransposition, mitotic errors, and sterile inflammation, which collectively disrupt genome integrity. The characterization of altered epigenetic homeostasis at retroelements in cancer cells also reveals new epigenetic targets whose inactivation can bolster responses to cancer therapies. Recent discoveries reviewed here frame reactivated retroelements as both drivers of tumorigenesis and therapy responses, where their reactivation by emerging epigenetic therapies can potentiate immune checkpoint blockade, cancer vaccines, and other standard therapies.\",\"PeriodicalId\":54233,\"journal\":{\"name\":\"Annual Review of Cancer Biology-Series\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2020-03-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1146/annurev-cancerbio-030419-033525\",\"citationCount\":\"34\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Annual Review of Cancer Biology-Series\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1146/annurev-cancerbio-030419-033525\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual Review of Cancer Biology-Series","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1146/annurev-cancerbio-030419-033525","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ONCOLOGY","Score":null,"Total":0}
Reactivation of Endogenous Retroelements in Cancer Development and Therapy
Domesticated retroelements contribute extensively as regulatory elements within host gene networks. Upon germline integration, retroelement mobilization is restricted through epigenetic silencing, mutational degradation, and innate immune defenses described as the viral mimicry response. Recent discoveries reveal how early events in tumorigenesis reactivate retroelements to facilitate onco-exaptation, replication stress, retrotransposition, mitotic errors, and sterile inflammation, which collectively disrupt genome integrity. The characterization of altered epigenetic homeostasis at retroelements in cancer cells also reveals new epigenetic targets whose inactivation can bolster responses to cancer therapies. Recent discoveries reviewed here frame reactivated retroelements as both drivers of tumorigenesis and therapy responses, where their reactivation by emerging epigenetic therapies can potentiate immune checkpoint blockade, cancer vaccines, and other standard therapies.
期刊介绍:
The Annual Review of Cancer Biology offers comprehensive reviews on various topics within cancer research, covering pivotal and emerging areas in the field. As our understanding of cancer's fundamental mechanisms deepens and more findings transition into targeted clinical treatments, the journal is structured around three main themes: Cancer Cell Biology, Tumorigenesis and Cancer Progression, and Translational Cancer Science. The current volume of this journal has transitioned from gated to open access through Annual Reviews' Subscribe to Open program, ensuring all articles are published under a CC BY license.