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Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
TLDR
BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage. Expand
A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing
TLDR
A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors. Expand
Inhibition of poly(ADP-ribose) polymerase in tumors from BRCA mutation carriers.
TLDR
Olaparib has few of the adverse effects of conventional chemotherapy, inhibits PARP, and has antitumor activity in cancer associated with the BRCA1 or BRCa2 mutation. Expand
Hallmarks of 'BRCAness' in sporadic cancers
TLDR
There are properties that define 'BRCAness' — that is, traits that some sporadic cancers share with those occurring in either BRCA1- or BRCa2-mutation carriers, which might have important implications for the clinical management of these cancers. Expand
Identification of the breast cancer susceptibility gene BRCA2
TLDR
The identification of a gene in which six different germline mutations in breast cancer families that are likely to be due to BRCA2 are detected, and results indicate that this is the BRC a2 gene. Expand
The DNA damage response and cancer therapy
TLDR
A better understanding of the cellular response to DNA damage will not only inform the knowledge of cancer development but also help to refine the classification as well as the treatment of the disease. Expand
CYLD is a deubiquitinating enzyme that negatively regulates NF-κB activation by TNFR family members
TLDR
Results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-κB that is required for appropriate cellular homeostasis of skin appendages. Expand
Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction
TLDR
These studies establish the importance of LKB1 in regulating AMPK activity and cellular energy levels in response to contraction and phenformin and reduce phosphorylation and activation of AMPKα2. Expand
Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition.
TLDR
The results indicate that PARP inhibition might be a useful therapeutic strategy not only for the treatment of BRCA mutation-associated tumors but also for a wider range of tumors bearing a variety of deficiencies in the HR pathway or displaying properties of 'BRCAness. Expand
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