{"title":"BRCA1在胶质母细胞瘤发病中的作用。","authors":"Emirhan Harbi, Michael Aschner","doi":"10.1007/s13402-024-01024-7","DOIUrl":null,"url":null,"abstract":"<p><p>BRCA1 (Breast Cancer 1) is a tumor suppressor gene with a role in DNA repair by Homologous Recombination (HR), and maintenance of genomic stability that is frequently investigated in breast, prostate, and ovarian cancers. BRCA1 mutations or dysregulation in glioblastoma can lead to impaired DNA repair mechanisms, resulting in tumor progression and resistance to standard therapies. Several studies have shown that BRCA1 expression is altered, albeit rarely, in glioblastoma, leading to poor prognosis and increased tumor aggressiveness. In addition, the communication of BRCA1 with other molecular pathways such as p53 and PTEN further complicates its role in glioblastoma pathogenesis. Targeting BRCA1-related pathways in these cases has shown the potential to improve the efficacy of standard treatments, including radiotherapy and chemotherapy. The development of (Poly (ADP-ribose) Polymerase) PARP inhibitors that exploit the lack of HR also offers a therapeutic approach to glioblastoma patients with BRCA1 mutations. Despite these advances, the heterogeneity of glioblastoma and its complex tumor microenvironment make the translation of such approaches into clinical practice still challenging, and there is an \"unmet need\". This review discusses the current mechanisms of etiology and potential treatment of BRCA1-related glioblastoma.</p>","PeriodicalId":49223,"journal":{"name":"Cellular Oncology","volume":" ","pages":"2091-2098"},"PeriodicalIF":4.9000,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Role of BRCA1 in glioblastoma etiology.\",\"authors\":\"Emirhan Harbi, Michael Aschner\",\"doi\":\"10.1007/s13402-024-01024-7\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>BRCA1 (Breast Cancer 1) is a tumor suppressor gene with a role in DNA repair by Homologous Recombination (HR), and maintenance of genomic stability that is frequently investigated in breast, prostate, and ovarian cancers. BRCA1 mutations or dysregulation in glioblastoma can lead to impaired DNA repair mechanisms, resulting in tumor progression and resistance to standard therapies. Several studies have shown that BRCA1 expression is altered, albeit rarely, in glioblastoma, leading to poor prognosis and increased tumor aggressiveness. In addition, the communication of BRCA1 with other molecular pathways such as p53 and PTEN further complicates its role in glioblastoma pathogenesis. Targeting BRCA1-related pathways in these cases has shown the potential to improve the efficacy of standard treatments, including radiotherapy and chemotherapy. The development of (Poly (ADP-ribose) Polymerase) PARP inhibitors that exploit the lack of HR also offers a therapeutic approach to glioblastoma patients with BRCA1 mutations. Despite these advances, the heterogeneity of glioblastoma and its complex tumor microenvironment make the translation of such approaches into clinical practice still challenging, and there is an \\\"unmet need\\\". This review discusses the current mechanisms of etiology and potential treatment of BRCA1-related glioblastoma.</p>\",\"PeriodicalId\":49223,\"journal\":{\"name\":\"Cellular Oncology\",\"volume\":\" \",\"pages\":\"2091-2098\"},\"PeriodicalIF\":4.9000,\"publicationDate\":\"2024-12-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13402-024-01024-7\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/12/10 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13402-024-01024-7","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/12/10 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
BRCA1 (Breast Cancer 1)是一种肿瘤抑制基因,在通过同源重组(Homologous Recombination, HR)修复DNA和维持基因组稳定性中发挥作用,在乳腺癌、前列腺癌和卵巢癌中经常被研究。胶质母细胞瘤中的BRCA1突变或失调可导致DNA修复机制受损,导致肿瘤进展和对标准治疗的耐药性。几项研究表明,BRCA1表达在胶质母细胞瘤中发生改变(尽管很少),导致预后不良和肿瘤侵袭性增加。此外,BRCA1与p53、PTEN等其他分子通路的通讯使其在胶质母细胞瘤发病中的作用进一步复杂化。在这些病例中,靶向brca1相关通路已显示出提高标准治疗(包括放疗和化疗)疗效的潜力。利用HR缺乏的聚(adp核糖)聚合酶PARP抑制剂的开发也为BRCA1突变的胶质母细胞瘤患者提供了一种治疗方法。尽管取得了这些进展,但胶质母细胞瘤的异质性及其复杂的肿瘤微环境使得这些方法转化为临床实践仍然具有挑战性,并且存在“未满足的需求”。本文综述了brca1相关胶质母细胞瘤的病因机制和潜在治疗方法。
BRCA1 (Breast Cancer 1) is a tumor suppressor gene with a role in DNA repair by Homologous Recombination (HR), and maintenance of genomic stability that is frequently investigated in breast, prostate, and ovarian cancers. BRCA1 mutations or dysregulation in glioblastoma can lead to impaired DNA repair mechanisms, resulting in tumor progression and resistance to standard therapies. Several studies have shown that BRCA1 expression is altered, albeit rarely, in glioblastoma, leading to poor prognosis and increased tumor aggressiveness. In addition, the communication of BRCA1 with other molecular pathways such as p53 and PTEN further complicates its role in glioblastoma pathogenesis. Targeting BRCA1-related pathways in these cases has shown the potential to improve the efficacy of standard treatments, including radiotherapy and chemotherapy. The development of (Poly (ADP-ribose) Polymerase) PARP inhibitors that exploit the lack of HR also offers a therapeutic approach to glioblastoma patients with BRCA1 mutations. Despite these advances, the heterogeneity of glioblastoma and its complex tumor microenvironment make the translation of such approaches into clinical practice still challenging, and there is an "unmet need". This review discusses the current mechanisms of etiology and potential treatment of BRCA1-related glioblastoma.
期刊介绍:
The Official Journal of the International Society for Cellular Oncology
Focuses on translational research
Addresses the conversion of cell biology to clinical applications
Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions.
A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients.
In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.