Role of BRCA1 in glioblastoma etiology.

Cell Oncol (Dordr)

Department of Molecular Pharmacology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.

Published: December 2024

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.

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13402-024-01024-7DOI Listing

Publication Analysis

Top Keywords

dna repair
8
brca1 mutations
8
glioblastoma
7
brca1
5
role brca1
4
brca1 glioblastoma
4
glioblastoma etiology
4
etiology brca1
4
brca1 breast
4
breast cancer
4

Similar Publications

Genome engineering with Cas9 and AAV repair templates, successes and pitfalls.

Mamm Genome

January 2025

CNRS, INSERM, CELPHEDIA, Institut Clinique de la Souris (ICS), Université de Strasbourg, Illkirch, PHENOMIN, France.

Genome editing, in particular the CRISPR/Cas9 system, is widely used to generate new animal models. However, the generation of mutations, such as conditional knock-out or knock-in, can remain complex and inefficient, in particular because of the difficulty to deliver the donor DNA (single or double stranded) into the nucleus of fertilized oocytes. The use of recombinant adeno-associated viruses (rAAV) as donor DNA is a rapidly developing approach that promises to improve the efficiency of creation of animal models.

View Article and Find Full Text PDF

Purpose: More active high-dose chemotherapy (HDC) regimens are needed for autologous stem-cell transplantation (ASCT) for refractory lymphomas. Seeking HDC enhancement with a poly(ADP-ribose) polymerase (PARP) inhibitor, we observed marked synergy between olaparib and vorinostat/gemcitabine/busulfan/melphalan (GemBuMel) against lymphoma cell lines, mediated by inhibition of DNA damage repair. Our preclinical work led us to clinically study olaparib/vorinostat/GemBuMel with ASCT.

View Article and Find Full Text PDF

Discovery of WDR5-MLL1 and HDAC Dual-Target Inhibitors for the Treatment of Acute Myeloid Leukemia.

J Med Chem

January 2025

Jiangsu Key Laboratory of Drug Design and Optimization and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.

Targeting the WDR5-MLL1 protein-protein interaction (PPI) is considered to be an effective approach for the treatment of MLL-rearranged leukemia. However, interfering with WDR5-MLL1 PPI reduces methylated H3K4 levels and induces a decline in acetylated H3 levels, which may contribute to the suboptimal cellular efficacy of WDR5 inhibitors. We observed that cotreatment with WDR5-MLL1 PPI and HDAC inhibitors augmented the antiproliferative effect in MV-4-11 cells.

View Article and Find Full Text PDF

We investigated if selected polymorphisms in DNA repair genes modify the association between exposure to particulate matter ≤ 10 micron in diameter (PM) and breast cancer (BCa) risk. We included 150,929 postmenopausal women (5,969 with BCa) from UK Biobank, a population-based prospective cohort. Cancer diagnoses were ascertained through the linkage to the UK National Health Service Central Registers.

View Article and Find Full Text PDF

Changes in the copy number of large genomic regions, termed copy number variations (CNVs), contribute to important phenotypes in many organisms. CNVs are readily identified using conventional approaches when present in a large fraction of the cell population. However, CNVs that are present in only a few genomes across a population are often overlooked but important; if beneficial under specific conditions, a de novo CNV that arises in a single genome can expand during selection to create a larger population of cells with novel characteristics.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!