Author pages are created from data sourced from our academic publisher partnerships and public sources.
Share This Author
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
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
Deficiency in the repair of DNA damage by homologous recombination and sensitivity to poly(ADP-ribose) polymerase inhibition.
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
BRCA2-deficient CAPAN-1 cells are extremely sensitive to the inhibition of poly (ADP-ribose) polymerase: An issue of potency
- N. Mccabe, C. Lord, A. Tutt, N. Martin, Graeme C M Smith, A. Ashworth
- Biology, Medicine
- Cancer biology & therapy
- 23 June 2005
It is shown that CAPAN-1 cells are in fact very sensitive to the potent PARP inhibitors KU0058684 (IC50 3.2nM) and K U0058948 (IC 50 3.4nM), and treatment with potent ParP inhibitors remains an exciting potential therapy for cancers involving BRCA1 or BRCa2 deficiency. Expand
DNA Polymerases as Potential Therapeutic Targets for Cancers Deficient in the DNA Mismatch Repair Proteins MSH2 or MLH1
Synthetic sickness/lethality can be exploited to develop therapeutic strategies for cancer and deficiency in MSH2 is SSL with inhibition of the DNA polymerase POLB, whereas deficiency in MLH1 isSSL with DNA polymerases POLG inhibition. Expand
Activation of STING-Dependent Innate Immune Signaling By S-Phase-Specific DNA Damage in Breast Cancer
- E. Parkes, S. Walker, +12 authors R. Kennedy
- Medicine, Biology
- Journal of the National Cancer Institute
- 5 October 2016
A novel mechanism of immune infiltration in DDRD tumors, independent of neoantigen production is proposed, and activation of this pathway and associated PD-L1 expression may explain the paradoxical lack of T-cell-mediated cytotoxicity observed in DDRd tumors. Expand
Potentiation of inflammatory CXCL8 signalling sustains cell survival in PTEN-deficient prostate carcinoma.
PTEN loss induces a selective upregulation of CXCL8 signalling that sustains the growth and survival of PTEN-deficient prostate epithelium, and is detected in regions displaying atypical cytologic features in wild-type PTEN (Pten(WT)) glands. Expand
Exploiting the DNA repair defect in BRCA mutant cells in the design of new therapeutic strategies for cancer.
- A. Tutt, C. Lord, +6 authors A. Ashworth
- Biology, Medicine
- Cold Spring Harbor symposia on quantitative…
These efforts are described, based on understanding the DNA repair defects in BRCAdeficient cells, to define the optimal existing treatment for cancers arising from BRCA mutation carriers and the development of novel therapeutic approaches. Expand
Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer
- N. Mccabe, M. Cerone, T. Ohishi, H. Seimiya, C. Lord, A. Ashworth
- Biology, Medicine
- 19 March 2009
It is shown that inhibition of the telomere-associated protein, Tankyrase 1, is also selectively lethal with BRCA deficiency, and it is proposed that suppression of Tankyrases 1 could be therapeutically exploited in BRCa-associated cancers. Expand
BRCA1 Regulates the Interferon γ-mediated Apoptotic Response*
BRCA1 is identified as a component of the IFN-γ-regulated signaling pathway and suggests that BRCA 1 may play a role in the regulation of IFN -γ-mediated apoptosis. Expand
BRCA1 regulates the interferon gamma-mediated apoptotic response.
- H. Andrews, P. Mullan, +9 authors D. Harkin
- Chemistry, Medicine
- The Journal of biological chemistry
BRCA1 is identified as a component of the IFN-gamma-regulated signaling pathway and it is suggested that BRCA 1 may play a role in the regulation ofIFN-Gamma-mediated apoptosis. Expand