{"title":"跨年龄组前列腺癌的分子景观:对预后和治疗结果的影响。","authors":"Magdalena Julita Orzechowska, Andrzej K Bednarek","doi":"10.3390/ijms26199777","DOIUrl":null,"url":null,"abstract":"<p><p>Prostate cancer (PC) has long been considered a disease of older men. Still, a significant and concerning rise in diagnoses among younger men has revealed a biologically distinct and more aggressive clinical entity: early-onset prostate cancer (EO-PC). This comprehensive review synthesizes the molecular and clinical evidence to demonstrate that PC is not a single disease, but a collection of distinct entities delineated by patient age. EO-PC is characterized by a strong genetic component, unique fusion events like <i>TMPRSS2-ERG</i>, and a highly plastic phenotype driven by intense Notch signaling and a hybrid epithelial-to-mesenchymal transition. In stark contrast, late-onset prostate cancer (LO-PC) is defined by a higher mutational burden, an epigenetic \"field defect\" that accumulates with age, and a predominantly immunosuppressive tumor microenvironment. These profound biological differences have significant implications for diagnosis, prognosis, and therapeutic strategies. Traditional prognostic tools, such as the Gleason score, are often insufficient to capture the full spectrum of risk in younger men. The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"26 19","pages":""},"PeriodicalIF":4.9000,"publicationDate":"2025-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524801/pdf/","citationCount":"0","resultStr":"{\"title\":\"Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes.\",\"authors\":\"Magdalena Julita Orzechowska, Andrzej K Bednarek\",\"doi\":\"10.3390/ijms26199777\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Prostate cancer (PC) has long been considered a disease of older men. Still, a significant and concerning rise in diagnoses among younger men has revealed a biologically distinct and more aggressive clinical entity: early-onset prostate cancer (EO-PC). This comprehensive review synthesizes the molecular and clinical evidence to demonstrate that PC is not a single disease, but a collection of distinct entities delineated by patient age. EO-PC is characterized by a strong genetic component, unique fusion events like <i>TMPRSS2-ERG</i>, and a highly plastic phenotype driven by intense Notch signaling and a hybrid epithelial-to-mesenchymal transition. In stark contrast, late-onset prostate cancer (LO-PC) is defined by a higher mutational burden, an epigenetic \\\"field defect\\\" that accumulates with age, and a predominantly immunosuppressive tumor microenvironment. These profound biological differences have significant implications for diagnosis, prognosis, and therapeutic strategies. Traditional prognostic tools, such as the Gleason score, are often insufficient to capture the full spectrum of risk in younger men. The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.</p>\",\"PeriodicalId\":14156,\"journal\":{\"name\":\"International Journal of Molecular Sciences\",\"volume\":\"26 19\",\"pages\":\"\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2025-10-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12524801/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Molecular Sciences\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.3390/ijms26199777\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Molecular Sciences","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.3390/ijms26199777","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
Molecular Landscape of Prostate Cancer Across Age Groups: Impact on Prognosis and Treatment Outcomes.
Prostate cancer (PC) has long been considered a disease of older men. Still, a significant and concerning rise in diagnoses among younger men has revealed a biologically distinct and more aggressive clinical entity: early-onset prostate cancer (EO-PC). This comprehensive review synthesizes the molecular and clinical evidence to demonstrate that PC is not a single disease, but a collection of distinct entities delineated by patient age. EO-PC is characterized by a strong genetic component, unique fusion events like TMPRSS2-ERG, and a highly plastic phenotype driven by intense Notch signaling and a hybrid epithelial-to-mesenchymal transition. In stark contrast, late-onset prostate cancer (LO-PC) is defined by a higher mutational burden, an epigenetic "field defect" that accumulates with age, and a predominantly immunosuppressive tumor microenvironment. These profound biological differences have significant implications for diagnosis, prognosis, and therapeutic strategies. Traditional prognostic tools, such as the Gleason score, are often insufficient to capture the full spectrum of risk in younger men. The divergent molecular landscapes of EO-PC and LO-PC necessitate a fundamental shift from a standard approach to an age-aware precision medicine framework. This review highlights key therapeutic targets and underscores the critical need for a new paradigm in PC management to improve patient outcomes.
期刊介绍:
The International Journal of Molecular Sciences (ISSN 1422-0067) provides an advanced forum for chemistry, molecular physics (chemical physics and physical chemistry) and molecular biology. It publishes research articles, reviews, communications and short notes. Our aim is to encourage scientists to publish their theoretical and experimental results in as much detail as possible. Therefore, there is no restriction on the length of the papers or the number of electronics supplementary files. For articles with computational results, the full experimental details must be provided so that the results can be reproduced. Electronic files regarding the full details of the calculation and experimental procedure, if unable to be published in a normal way, can be deposited as supplementary material (including animated pictures, videos, interactive Excel sheets, software executables and others).