Publications by authors named "R Hromas"
Article Synopsis
- BAP1 mutations lead to a loss of function affecting cell cycle and DNA repair, making patients potentially responsive to PARP inhibitors like niraparib.
- A phase II trial evaluated niraparib in patients with advanced tumors likely to have mBAP1 mutations, focusing on response rates, progression-free survival, and overall survival.
- Despite not meeting the primary efficacy goal, some clinical benefits were observed in patients with confirmed mBAP1 mutations, suggesting the need for further research.
Background And Objective: The etiology of prostate cancer (PC) is multifactorial and poorly understood. It has been suggested that colibactin-producing Escherichia coli positive for the pathogenicity island pks (pks) initiate cancers via induction of genomic instability. In PC, androgens promote oncogenic translocations.
View Article and Find Full Text PDFHomologous recombination (HR) is a highly conserved tool for the removal of DNA double-strand breaks (DSBs) and the preservation of stalled and damaged DNA replication forks. Successful completion of HR requires the tumor suppressor BRCA2. Germline mutations in BRCA2 lead to familial breast, ovarian, and other cancers, underscoring the importance of this protein for maintaining genome stability.
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- - The process of DNA double-strand break repair through homologous recombination requires end resection to create a single-stranded DNA template, involving the RAD51 recombinase and other proteins, with BRCA1-BARD1 being crucial for this step.
- - DNA end resection is performed by three key nucleases: EXO1, DNA2 (in partnership with BLM or WRN helicases), working together to resect the DNA ends, while BRCA1-BARD1’s role in regulating this process is critically examined.
- - Research shows that BRCA1-BARD1 directly interacts with EXO1, BLM, and WRN, enhancing their activity, and certain BARD1 mutations impairing DNA
Overexpression of BCL-xL and BCL-2 play key roles in tumorigenesis and cancer drug resistance. Advances in PROTAC technology facilitated recent development of the first BCL-xL/BCL-2 dual degrader, 753b, a VHL-based degrader with improved potency and reduced toxicity compared to previous small molecule inhibitors. Here, we determine crystal structures of VHL/753b/BCL-xL and VHL/753b/BCL-2 ternary complexes.
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