Browsing Molecular Pathology by author "Pettitt, Stephen"
Now showing items 21-26 of 26
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Phase I Trial of the PARP Inhibitor Olaparib and AKT Inhibitor Capivasertib in Patients with BRCA1/2- and Non-BRCA1/2-Mutant Cancers.
Yap, TA; Kristeleit, R; Michalarea, V; Pettitt, SJ; Lim, JSJ; et al. (AMER ASSOC CANCER RESEARCH, 2020-10-01)Preclinical studies have demonstrated synergy between PARP and PI3K/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing ... -
Polθ inhibitors elicit BRCA-gene synthetic lethality and target PARP inhibitor resistance.
Zatreanu, D; Robinson, HMR; Alkhatib, O; Boursier, M; Finch, H; et al. (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 ... -
Sirtuin inhibition is synthetic lethal with BRCA1 or BRCA2 deficiency.
Bajrami, I; Walker, C; Krastev, DB; Weekes, D; Song, F; et al. (NATURE PORTFOLIO, 2021-11-08)PARP enzymes utilise NAD+ as a co-substrate for their enzymatic activity. Inhibition of PARP1 is synthetic lethal with defects in either BRCA1 or BRCA2. In order to assess whether other genes implicated in NAD+ metabolism ... -
The CST Complex Mediates End Protection at Double-Strand Breaks and Promotes PARP Inhibitor Sensitivity in BRCA1-Deficient Cells.
Barazas, M; Annunziato, S; Pettitt, SJ; de Krijger, I; Ghezraoui, H; et al. (CELL PRESS, 2018-05-15)Selective elimination of BRCA1-deficient cells by inhibitors of poly(ADP-ribose) polymerase (PARP) is a prime example of the concept of synthetic lethality in cancer therapy. This interaction is counteracted by the restoration ... -
The shieldin complex mediates 53BP1-dependent DNA repair.
Noordermeer, SM; Adam, S; Setiaputra, D; Barazas, M; Pettitt, SJ; et al. (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, ... -
The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin.
Krastev, DB; Li, S; Sun, Y; Wicks, AJ; Hoslett, G; et al. (NATURE PORTFOLIO, 2022-01-01)Poly (ADP-ribose) polymerase (PARP) inhibitors elicit antitumour activity in homologous recombination-defective cancers by trapping PARP1 in a chromatin-bound state. How cells process trapped PARP1 remains unclear. Using ...