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Genome-wide characterization reveals complex interplay between TP53 and TP63 in response to genotoxic stress.
(OXFORD UNIV PRESS, 2014-01-01)
In response to genotoxic stress the TP53 tumour suppressor activates target gene expression to induce cell cycle arrest or apoptosis depending on the extent of DNA damage. These canonical activities can be repressed by ...
DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer.
(MASSACHUSETTS MEDICAL SOC, 2015-10-29)
BACKGROUND: Prostate cancer is a heterogeneous disease, but current treatments are not based on molecular stratification. We hypothesized that metastatic, castration-resistant prostate cancers with DNA-repair defects would ...
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
(NATURE RESEARCH, 2021-06-17)
To identify approaches to target DNA repair vulnerabilities in cancer, we discovered nanomolar potent, selective, low molecular weight (MW), allosteric inhibitors of the polymerase function of DNA polymerase Polθ, including ...
DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade.
(AMER SOC CLINICAL INVESTIGATION INC, 2018-04-02)
Synthetic lethality is an efficient mechanism-based approach to selectively target DNA repair defects. Excision repair cross-complementation group 1 (ERCC1) deficiency is frequently found in non-small-cell lung cancer ...
PARP inhibitors: Synthetic lethality in the clinic.
(AMER ASSOC ADVANCEMENT SCIENCE, 2017-03-17)
PARP inhibitors (PARPi), a cancer therapy targeting poly(ADP-ribose) polymerase, are the first clinically approved drugs designed to exploit synthetic lethality, a genetic concept proposed nearly a century ago. Tumors ...
Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity.
(IMPACT JOURNALS LLC, 2015-05-10)
Based on a series of basic, preclinical and clinical studies, the Poly (ADP-ribose) Polymerase 1 (PARP1) inhibitor, olaparib, has recently been approved for use in ovarian cancer patients with BRCA1 or BRCA2 mutations. By ...
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, ...
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) ...