Browsing Breast Cancer Research by author "Pettitt, Stephen"
Now showing items 21-32 of 32
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Modeling Therapy Resistance in BRCA1/2-Mutant Cancers.
Dréan, A; Williamson, CT; Brough, R; Brandsma, I; Menon, M; et al. (AMER ASSOC CANCER RESEARCH, 2017-09-01)Although PARP inhibitors target BRCA1- or BRCA2-mutant tumor cells, drug resistance is a problem. PARP inhibitor resistance is sometimes associated with the presence of secondary or "revertant" mutations in BRCA1 or BRCA2 ... -
PARP inhibition enhances tumor cell-intrinsic immunity in ERCC1-deficient non-small cell lung cancer.
Chabanon, RM; Muirhead, G; Krastev, DB; Adam, J; Morel, D; et al. (AMER SOC CLINICAL INVESTIGATION INC, 2019-03-01)The cyclic GMP-AMP synthase/stimulator of IFN genes (cGAS/STING) pathway detects cytosolic DNA to activate innate immune responses. Poly(ADP-ribose) polymerase inhibitors (PARPi) selectively target cancer cells with DNA ... -
PARP inhibitors and breast cancer: highlights and hang-ups
Pettitt, SJ; Lord, CJ (TAYLOR & FRANCIS LTD, 2018-01-01) -
Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors.
Yap, TA; O'Carrigan, B; Penney, MS; Lim, JS; Brown, JS; et al. (AMER SOC CLINICAL ONCOLOGY, 2020-06-22)PURPOSE: Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging ... -
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 ... -
Resistance to DNA repair inhibitors in cancer.
Baxter, JS; Zatreanu, D; Pettitt, SJ; Lord, CJ (WILEY, 2022-05-14)The DNA damage response (DDR) represents a complex network of proteins which detect and repair DNA damage, thereby maintaining the integrity of the genome and preventing the transmission of mutations and rearranged chromosomes ... -
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 ... -
SMG8/SMG9 Heterodimer Loss Modulates SMG1 Kinase to Drive ATR Inhibitor Resistance.
Llorca-Cardenosa, MJ; Aronson, LI; Krastev, DB; Nieminuszczy, J; Alexander, J; et al. (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 ... -
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 ...