{"title":"表型可塑性-替代转录程序驱动治疗耐药前列腺癌。","authors":"Jagpreet Singh Nanda, Praveen Koganti, Graziela Perri, Leigh Ellis","doi":"10.1615/CritRevOncog.2022043096","DOIUrl":null,"url":null,"abstract":"<p><p>Androgen deprivation therapy (ADT) that antagonizes androgen receptor (AR) signaling has made significant increases to overall survival of prostate cancer patients. However, ADT is not curative, and patients eventually progress to castration resistant disease (CRPC). It has become evident that a subset of prostate cancers acquire ADT resistance through mechanisms independent of AR alteration or reprogramming of AR signaling. This approximately involves a quarter of prostate cancers progressing on ADT. Collectively, these tumors evolve via phenotypic plasticity and display the activation of developmental and stemness gene signatures as well as transitional programs including an epithelial-mesenchymal phenotype. Currently, no successful treatments exist for prostate cancer patients to inhibit or reverse prostate tumor progression that utilizes mechanisms of epi-plasticity. This overview will discuss epigenetic mechanisms that mediate phenotypic plasticity and the potential for targeting the epigenome to create a novel direction for combination strategies involving epigenetic therapy to provide durable response.</p>","PeriodicalId":35617,"journal":{"name":"Critical Reviews in Oncogenesis","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353263/pdf/nihms-1904403.pdf","citationCount":"1","resultStr":"{\"title\":\"Phenotypic Plasticity - Alternate Transcriptional Programs Driving Treatment Resistant Prostate Cancer.\",\"authors\":\"Jagpreet Singh Nanda, Praveen Koganti, Graziela Perri, Leigh Ellis\",\"doi\":\"10.1615/CritRevOncog.2022043096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Androgen deprivation therapy (ADT) that antagonizes androgen receptor (AR) signaling has made significant increases to overall survival of prostate cancer patients. However, ADT is not curative, and patients eventually progress to castration resistant disease (CRPC). It has become evident that a subset of prostate cancers acquire ADT resistance through mechanisms independent of AR alteration or reprogramming of AR signaling. This approximately involves a quarter of prostate cancers progressing on ADT. Collectively, these tumors evolve via phenotypic plasticity and display the activation of developmental and stemness gene signatures as well as transitional programs including an epithelial-mesenchymal phenotype. Currently, no successful treatments exist for prostate cancer patients to inhibit or reverse prostate tumor progression that utilizes mechanisms of epi-plasticity. This overview will discuss epigenetic mechanisms that mediate phenotypic plasticity and the potential for targeting the epigenome to create a novel direction for combination strategies involving epigenetic therapy to provide durable response.</p>\",\"PeriodicalId\":35617,\"journal\":{\"name\":\"Critical Reviews in Oncogenesis\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2022-01-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10353263/pdf/nihms-1904403.pdf\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Critical Reviews in Oncogenesis\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.1615/CritRevOncog.2022043096\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"Biochemistry, Genetics and Molecular Biology\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Critical Reviews in Oncogenesis","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.1615/CritRevOncog.2022043096","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"Biochemistry, Genetics and Molecular Biology","Score":null,"Total":0}
Androgen deprivation therapy (ADT) that antagonizes androgen receptor (AR) signaling has made significant increases to overall survival of prostate cancer patients. However, ADT is not curative, and patients eventually progress to castration resistant disease (CRPC). It has become evident that a subset of prostate cancers acquire ADT resistance through mechanisms independent of AR alteration or reprogramming of AR signaling. This approximately involves a quarter of prostate cancers progressing on ADT. Collectively, these tumors evolve via phenotypic plasticity and display the activation of developmental and stemness gene signatures as well as transitional programs including an epithelial-mesenchymal phenotype. Currently, no successful treatments exist for prostate cancer patients to inhibit or reverse prostate tumor progression that utilizes mechanisms of epi-plasticity. This overview will discuss epigenetic mechanisms that mediate phenotypic plasticity and the potential for targeting the epigenome to create a novel direction for combination strategies involving epigenetic therapy to provide durable response.
期刊介绍:
The journal is dedicated to extensive reviews, minireviews, and special theme issues on topics of current interest in basic and patient-oriented cancer research. The study of systems biology of cancer with its potential for molecular level diagnostics and treatment implies competence across the sciences and an increasing necessity for cancer researchers to understand both the technology and medicine. The journal allows readers to adapt a better understanding of various fields of molecular oncology. We welcome articles on basic biological mechanisms relevant to cancer such as DNA repair, cell cycle, apoptosis, angiogenesis, tumor immunology, etc.