Now showing items 1-20 of 76

    • Analysis of Circulating Cell-Free DNA Identifies Multiclonal Heterogeneity of <i>BRCA2</i> Reversion Mutations Associated with Resistance to PARP Inhibitors. 

      Quigley, D; Alumkal, JJ; Wyatt, AW; Kothari, V; Foye, A; Lloyd, P; Aggarwal, R; Kim, W; Lu, E; Schwartzman, J; Beja, K; Annala, M; Das, R; Diolaiti, M; Pritchard, C; Thomas, G; Tomlins, S; Knudsen, K; Lord, CJ; Ryan, C; Youngren, J; Beer, TM; Ashworth, A; Small, EJ; Feng, FY (2017-09)
      Approximately 20% of metastatic prostate cancers harbor mutations in genes required for DNA repair by homologous recombination repair (HRR) such as <i>BRCA2</i> HRR defects confer synthetic lethality to PARP inhibitors ...
    • ATR inhibitors as a synthetic lethal therapy for tumours deficient in ARID1A. 

      Williamson, CT; Miller, R; Pemberton, HN; Jones, SE; Campbell, J; Konde, A; Badham, N; Rafiq, R; Brough, R; Gulati, A; Ryan, CJ; Francis, J; Vermulen, PB; Reynolds, AR; Reaper, PM; Pollard, JR; Ashworth, A; Lord, CJ (2016-12-13)
      Identifying genetic biomarkers of synthetic lethal drug sensitivity effects provides one approach to the development of targeted cancer therapies. Mutations in ARID1A represent one of the most common molecular alterations ...
    • ATR Is a Therapeutic Target in Synovial Sarcoma. 

      Jones, SE; Fleuren, EDG; Frankum, J; Konde, A; Williamson, CT; Krastev, DB; Pemberton, HN; Campbell, J; Gulati, A; Elliott, R; Menon, M; Selfe, JL; Brough, R; Pettitt, SJ; Niedzwiedz, W; van der Graaf, WTA; Shipley, J; Ashworth, A; Lord, CJ (2017-12)
      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 ...
    • Beyond DNA repair: the novel immunological potential of PARP inhibitors. 

      Chabanon, RM; Soria, J-C; Lord, CJ; Postel-Vinay, S (2019-01)
      Loss of excision repair cross-complementation group 1 (ERCC1), frequently found in lung cancer, and mutations in breast cancer type 1/2 susceptibility genes (<i>BRCA1/2</i>), often found in ovarian, breast and prostate ...
    • Biomarkers Associating with PARP Inhibitor Benefit in Prostate Cancer in the TOPARP-B Trial. 

      Carreira, S; Porta, N; Arce-Gallego, S; Seed, G; Llop-Guevara, A; Bianchini, D; Rescigno, P; Paschalis, A; Bertan, C; Baker, C; Goodall, J; Miranda, S; Riisnaes, R; Figueiredo, I; Ferreira, A; Pereira, R; Crespo, M; Gurel, B; Nava Rodrigues, D; Pettitt, SJ; Yuan, W; Serra, V; Rekowski, J; Lord, CJ; Hall, E; Mateo, J; de Bono, JS (2021-05-27)
      PARP inhibitors are approved for treating advanced prostate cancers (APCs) with various defective DNA repair genes; however, further studies to clinically qualify predictive biomarkers are warranted. Herein we analyzed ...
    • CancerGD: a resource for identifying and interpreting genetic dependencies in cancer 

      Bridgett, S; Campbell, J; Lord, C; Ryan, C (2016-10-26)
      Abstract Genes whose function is selectively essential in the presence of cancer associated genetic aberrations represent promising targets for the development of precision therapeutics. Here we present CancerGD ( ...
    • CancerGD: A Resource for Identifying and Interpreting Genetic Dependencies in Cancer. 

      Bridgett, S; Campbell, J; Lord, CJ; Ryan, CJ (2017-07-12)
      Genes whose function is selectively essential in the presence of cancer-associated genetic aberrations represent promising targets for the development of precision therapeutics. Here, we present CancerGD, a resource that ...
    • CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
      Activating KRAS mutations are found in approximately 20% of human cancers but no RAS-directed therapies are currently available. Here we describe a novel, robust, KRAS synthetic lethal interaction with the cyclin dependent ...
    • Cells Lacking the <i>RB1</i> Tumor Suppressor Gene Are Hyperdependent on Aurora B Kinase for Survival. 

      Oser, MG; Fonseca, R; Chakraborty, AA; Brough, R; Spektor, A; Jennings, RB; Flaifel, A; Novak, JS; Gulati, A; Buss, E; Younger, ST; McBrayer, SK; Cowley, GS; Bonal, DM; Nguyen, Q-D; Brulle-Soumare, L; Taylor, P; Cairo, S; Ryan, CJ; Pease, EJ; Maratea, K; Travers, J; Root, DE; Signoretti, S; Pellman, D; Ashton, S; Lord, CJ; Barry, ST; Kaelin, WG (2019-02)
      Small cell lung cancer (SCLC) accounts for 15% of lung cancers and is almost always linked to inactivating <i>RB1</i> and <i>TP53</i> mutations. SCLC frequently responds, albeit briefly, to chemotherapy. The canonical ...
    • Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. 

      Natrajan, R; Wilkerson, PM; Marchiò, C; Piscuoglio, S; Ng, CKY; Wai, P; Lambros, MB; Samartzis, EP; Dedes, KJ; Frankum, J; Bajrami, I; Kopec, A; Mackay, A; A'hern, R; Fenwick, K; Kozarewa, I; Hakas, J; Mitsopoulos, C; Hardisson, D; Lord, CJ; Kumar-Sinha, C; Ashworth, A; Weigelt, B; Sapino, A; Chinnaiyan, AM; Maher, CA; Reis-Filho, JS (2014-04)
      Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen ...
    • Chemosensitivity profiling of osteosarcoma tumour cell lines identifies a model of BRCAness. 

      Holme, H; Gulati, A; Brough, R; Fleuren, EDG; Bajrami, I; Campbell, J; Chong, IY; Costa-Cabral, S; Elliott, R; Fenton, T; Frankum, J; Jones, SE; Menon, M; Miller, R; Pemberton, HN; Postel-Vinay, S; Rafiq, R; Selfe, JL; von Kriegsheim, A; Munoz, AG; Rodriguez, J; Shipley, J; van der Graaf, WTA; Williamson, CT; Ryan, CJ; Pettitt, S; Ashworth, A; Strauss, SJ; Lord, CJ (2018-07-13)
      Osteosarcoma (OS) is an aggressive sarcoma, where novel treatment approaches are required. Genomic studies suggest that a subset of OS, including OS tumour cell lines (TCLs), exhibit genomic loss of heterozygosity (LOH) ...
    • Chemotherapy-induced senescent cancer cells engulf other cells to enhance their survival. 

      Tonnessen-Murray, CA; Frey, WD; Rao, SG; Shahbandi, A; Ungerleider, NA; Olayiwola, JO; Murray, LB; Vinson, BT; Chrisey, DB; Lord, CJ; Jackson, JG (2019-11)
      In chemotherapy-treated breast cancer, wild-type p53 preferentially induces senescence over apoptosis, resulting in a persisting cell population constituting residual disease that drives relapse and poor patient survival ...
    • Circulating Cell-Free DNA to Guide Prostate Cancer Treatment with PARP Inhibition. 

      Goodall, J; Mateo, J; Yuan, W; Mossop, H; Porta, N; Miranda, S; Perez-Lopez, R; Dolling, D; Robinson, DR; Sandhu, S; Fowler, G; Ebbs, B; Flohr, P; Seed, G; Rodrigues, DN; Boysen, G; Bertan, C; Atkin, M; Clarke, M; Crespo, M; Figueiredo, I; Riisnaes, R; Sumanasuriya, S; Rescigno, P; Zafeiriou, Z; Sharp, A; Tunariu, N; Bianchini, D; Gillman, A; Lord, CJ; Hall, E; Chinnaiyan, AM; Carreira, S; de Bono, JS; TOPARP-A investigators (2017-09)
      Biomarkers for more precise patient care are needed in metastatic prostate cancer. We have reported a phase II trial (TOPARP-A) of the PARP inhibitor olaparib in metastatic prostate cancer, demonstrating antitumor activity ...
    • Clinical <i>BRCA1/2</i> Reversion Analysis Identifies Hotspot Mutations and Predicted Neoantigens Associated with Therapy Resistance. 

      Pettitt, SJ; Frankum, JR; Punta, M; Lise, S; Alexander, J; Chen, Y; Yap, TA; Haider, S; Tutt, ANJ; Lord, CJ (2020-10)
      Reversion mutations in <i>BRCA1</i> or <i>BRCA2</i> are associated with resistance to PARP inhibitors and platinum. To better understand the nature of these mutations, we collated, codified, and analyzed more than 300 ...
    • Clonal diversity of MYC amplification evaluated by fluorescent in situ hybridisation and digital droplet polymerase chain reaction in oesophagogastric cancer: Results from a prospective clinical trial screening programme. 

      Davidson, M; Aronson, LI; Howard-Reeves, J; Bryant, H; Cutts, RJ; Hulkki-Wilson, S; Kouvelakis, K; Kalaitzaki, E; Watkins, D; Starling, N; Rao, S; Cardenosa, ML; Begum, R; Rana, I; Lazaro-Alcausi, R; Terlizzo, M; Wotherspoon, A; Brown, G; Swansbury, J; Lord, CJ; Cunningham, D; Chau, I; Chong, IY (2019-11)
      <h4>Introduction</h4>The MYC proto-oncogene is among the most commonly dysregulated genes in human cancers. We report screening data from the iMYC trial, an ongoing phase II study assessing ibrutinib monotherapy in advanced ...
    • A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events. 

      Ryan, CJ; Kennedy, S; Bajrami, I; Matallanas, D; Lord, CJ (2017-10-11)
      Protein complexes are responsible for the bulk of activities within the cell, but how their behavior and abundance varies across tumors remains poorly understood. By combining proteomic profiles of breast tumors with a ...
    • Complementary genetic screens identify the E3 ubiquitin ligase CBLC, as a modifier of PARP inhibitor sensitivity. 

      Frankum, J; Moudry, P; Brough, R; Hodny, Z; Ashworth, A; Bartek, J; Lord, CJ (2015-05)
      Based on a series of basic, preclinical and clinical studies, the Poly (ADP-ribose) Polymerase 1 (PARP1) inhibitor, olaparib, has recently been approved for use in ovarian cancer patients with BRCA1 or BRCA2 mutations. By ...
    • COMPOUNDS AND THEIR USES 

      Newton, G; Lord, C (2013-02-21)
      The invention provides a compound that is an inhibitor of one or both of TBK1 and IKKe, or a down-regulator of the expression of one or both of TBK1 and IKKe, for use in a method of treating a cancer that is dependent on ...
    • Correction: CDK1 Is a Synthetic Lethal Target for KRAS Mutant Tumours. 

      Costa-Cabral, S; Brough, R; Konde, A; Aarts, M; Campbell, J; Marinari, E; Riffell, J; Bardelli, A; Torrance, C; Lord, CJ; Ashworth, A (2016-01)
    • Coupling bimolecular PARylation biosensors with genetic screens to identify PARylation targets. 

      Krastev, DB; Pettitt, SJ; Campbell, J; Song, F; Tanos, BE; Stoynov, SS; Ashworth, A; Lord, CJ (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 ...