Search
Now showing items 81-90 of 90
Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells.
(NATURE PUBLISHING GROUP, 2017-06-27)
BACKGROUND: Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 ...
SF3B1 hotspot mutations confer sensitivity to PARP inhibition by eliciting a defective replication stress response.
(NATURE PORTFOLIO, 2023-08-01)
SF3B1 hotspot mutations are associated with a poor prognosis in several tumor types and lead to global disruption of canonical splicing. Through synthetic lethal drug screens, we identify that SF3B1 mutant (SF3B1MUT) cells ...
The shieldin complex mediates 53BP1-dependent DNA repair.
(NATURE PUBLISHING GROUP, 2018-08-02)
53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and RIF14-9, ...
Longitudinal profiling identifies co-occurring BRCA1/2 reversions, TP53BP1, RIF1 and PAXIP1 mutations in PARP inhibitor-resistant advanced breast cancer.
(Elsevier BV, 2024-01-19)
BACKGROUND: Resistance to therapies that target homologous recombination deficiency (HRD) in breast cancer limits their overall effectiveness. Multiple, preclinically validated, mechanisms of resistance have been proposed, ...
MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells.
(CELL PRESS, 2023-05-30)
The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity ...
Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition.
(AMER ASSOC CANCER RESEARCH, 2017-09-01)
Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity ...
SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance.
(AMER ASSOC CANCER RESEARCH, 2022-11-02)
UNLABELLED: Gastric cancer represents the third leading cause of global cancer mortality and an area of unmet clinical need. Drugs that target the DNA damage response, including ATR inhibitors (ATRi), have been proposed ...
Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness.
(NATURE PORTFOLIO, 2018-07-13)
Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) ...
Cancer-associated FBXW7 loss is synthetic lethal with pharmacological targeting of CDC7.
(WILEY, 2023-10-22)
The F-box and WD repeat domain containing 7 (FBXW7) tumour suppressor gene encodes a substrate-recognition subunit of Skp, cullin, F-box (SCF)-containing complexes. The tumour-suppressive role of FBXW7 is ascribed to its ...
Functional annotation of the 2q35 breast cancer risk locus implicates a structural variant in influencing activity of a long-range enhancer element.
(CELL PRESS, 2021-07-01)
A combination of genetic and functional approaches has identified three independent breast cancer risk loci at 2q35. A recent fine-scale mapping analysis to refine these associations resulted in 1 (signal 1), 5 (signal 2), ...