Browsing by author "Krastev, Dragomir"

Now showing items 1-12 of 12

    • ATR Is a Therapeutic Target in Synovial Sarcoma. 

      Jones, SE; Fleuren, EDG; Frankum, J; Konde, A; Williamson, CT; et al. (AMER ASSOC CANCER RESEARCH, 2017-12-15)
      Synovial sarcoma (SS) is an aggressive soft-tissue malignancy characterized by expression of SS18-SSX fusions, where treatment options are limited. To identify therapeutically actionable genetic dependencies in SS, we ...

    • Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. 

      Krastev, DB; Pettitt, SJ; Campbell, J; Song, F; Tanos, BE; et al. (NATURE PUBLISHING GROUP, 2018-05-22)
      Poly (ADP-ribose)ylation is a dynamic protein modification that regulates multiple cellular processes. Here, we describe a system for identifying and characterizing PARylation events that exploits the ability of a PBZ ...

    • DNA repair deficiency sensitizes lung cancer cells to NAD+ biosynthesis blockade. 

      Touat, M; Sourisseau, T; Dorvault, N; Chabanon, RM; Garrido, M; et al. (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 ...

    • E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer. 

      Bajrami, I; Marlow, R; van de Ven, M; Brough, R; Pemberton, HN; et al. (AMER ASSOC CANCER RESEARCH, 2018-04-01)
      The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells ...

    • Genome-wide and high-density CRISPR-Cas9 screens identify point mutations in PARP1 causing PARP inhibitor resistance. 

      Pettitt, SJ; Krastev, DB; Brandsma, I; Dréan, A; Song, F; et al. (NATURE PUBLISHING GROUP, 2018-05-01)
      Although PARP inhibitors (PARPi) target homologous recombination defective tumours, drug resistance frequently emerges, often via poorly understood mechanisms. Here, using genome-wide and high-density CRISPR-Cas9 ...

    • Genome-wide barcoded transposon screen for cancer drug sensitivity in haploid mouse embryonic stem cells. 

      Pettitt, SJ; Krastev, DB; Pemberton, HN; Fontebasso, Y; Frankum, J; et al. (NATURE PUBLISHING GROUP, 2017-03-01)
      We describe a screen for cellular response to drugs that makes use of haploid embryonic stem cells. We generated ten libraries of mutants with piggyBac gene trap transposon integrations, totalling approximately 100,000 ...

    • A HUWE1 defect causes PARP inhibitor resistance by modulating the BRCA1-∆11q splice variant. 

      Pettitt, SJ; Shao, N; Zatreanu, D; Frankum, J; Bajrami, I; et al. (SPRINGERNATURE, 2023-09-01)
      Although PARP inhibitors (PARPi) now form part of the standard-of-care for the treatment of homologous recombination defective cancers, de novo and acquired resistance limits their overall effectiveness. Previously, ...

    • 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 ...

    • 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 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 ...