Now showing items 1-20 of 48

    • Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer. 

      Rafii, S; Gourley, C; Kumar, R; Geuna, E; Ern Ang, J; Rye, T; Chen, L-M; Shapira-Frommer, R; Friedlander, M; Matulonis, U; De Greve, J; Oza, AM; Banerjee, S; Molife, LR; Gore, ME; Kaye, SB; Yap, TA (2017-07)
      The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately ...
    • BRCA1 and BRCA2 tumor suppressors protect against endogenous acetaldehyde toxicity. 

      Tacconi, EM; Lai, X; Folio, C; Porru, M; Zonderland, G; Badie, S; Michl, J; Sechi, I; Rogier, M; Matía García, V; Batra, AS; Rueda, OM; Bouwman, P; Jonkers, J; Ryan, A; Reina-San-Martin, B; Hui, J; Tang, N; Bruna, A; Biroccio, A; Tarsounas, M (2017-10)
      Maintenance of genome integrity requires the functional interplay between Fanconi anemia (FA) and homologous recombination (HR) repair pathways. Endogenous acetaldehyde, a product of cellular metabolism, is a potent source ...
    • The BRCA1-Δ11q Alternative Splice Isoform Bypasses Germline Mutations and Promotes Therapeutic Resistance to PARP Inhibition and Cisplatin. 

      Wang, Y; Bernhardy, AJ; Cruz, C; Krais, JJ; Nacson, J; Nicolas, E; Peri, S; van der Gulden, H; van der Heijden, I; O'Brien, SW; Zhang, Y; Harrell, MI; Johnson, SF; Candido Dos Reis, FJ; Pharoah, PDP; Karlan, B; Gourley, C; Lambrechts, D; Chenevix-Trench, G; Olsson, H; Benitez, JJ; Greene, MH; Gore, M; Nussbaum, R; Sadetzki, S; Gayther, SA; Kjaer, SK; kConFab Investigators; D'Andrea, AD; Shapiro, GI; Wiest, DL; Connolly, DC; Daly, MB; Swisher, EM; Bouwman, P; Jonkers, J; Balmaña, J; Serra, V; Johnson, N (2016-05)
      Breast and ovarian cancer patients harboring BRCA1/2 germline mutations have clinically benefitted from therapy with PARP inhibitor (PARPi) or platinum compounds, but acquired resistance limits clinical impact. In this ...
    • Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial. 

      Tutt, A; Tovey, H; Cheang, MCU; Kernaghan, S; Kilburn, L; Gazinska, P; Owen, J; Abraham, J; Barrett, S; Barrett-Lee, P; Brown, R; Chan, S; Dowsett, M; Flanagan, JM; Fox, L; Grigoriadis, A; Gutin, A; Harper-Wynne, C; Hatton, MQ; Hoadley, KA; Parikh, J; Parker, P; Perou, CM; Roylance, R; Shah, V; Shaw, A; Smith, IE; Timms, KM; Wardley, AM; Wilson, G; Gillett, C; Lanchbury, JS; Ashworth, A; Rahman, N; Harries, M; Ellis, P; Pinder, SE; Bliss, JM (2018-05)
      Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs ...
    • 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) ...
    • A Cost-Effectiveness Evaluation of Germline BRCA1 and BRCA2 Testing in UK Women with Ovarian Cancer. 

      Eccleston, A; Bentley, A; Dyer, M; Strydom, A; Vereecken, W; George, A; Rahman, N (2017-04)
      OBJECTIVES:To evaluate the long-term cost-effectiveness of germline BRCA1 and BRCA2 (collectively termed "BRCA") testing in women with epithelial ovarian cancer, and testing for the relevant mutation in first- and second-degree ...
    • CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions. 

      Zimmermann, M; Murina, O; Reijns, MAM; Agathanggelou, A; Challis, R; Tarnauskaitė, Ž; Muir, M; Fluteau, A; Aregger, M; McEwan, A; Yuan, W; Clarke, M; Lambros, MB; Paneesha, S; Moss, P; Chandrashekhar, M; Angers, S; Moffat, J; Brunton, VG; Hart, T; de Bono, J; Stankovic, T; Jackson, AP; Durocher, D (2018-07-04)
      The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in ...
    • CSN and CAVA: variant annotation tools for rapid, robust next-generation sequencing analysis in the clinical setting. 

      Münz, M; Ruark, E; Renwick, A; Ramsay, E; Clarke, M; Mahamdallie, S; Cloke, V; Seal, S; Strydom, A; Lunter, G; Rahman, N (2015-07-28)
      Next-generation sequencing (NGS) offers unprecedented opportunities to expand clinical genomics. It also presents challenges with respect to integration with data from other sequencing methods and historical data. Provision ...
    • 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; Roobol, SJ; Lutz, C; Frankum, J; Song, FF; Brough, R; Evers, B; Gogola, E; Bhin, J; van de Ven, M; van Gent, DC; Jacobs, JJL; Chapman, R; Lord, CJ; Jonkers, J; Rottenberg, S (2018-05)
      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 ...
    • A decade of clinical development of PARP inhibitors in perspective. 

      Mateo, J; Lord, CJ; Serra, V; Tutt, A; Balmaña, J; Castroviejo-Bermejo, M; Cruz, C; Oaknin, A; Kaye, SB; de Bono, JS (2019-09)
      Genomic instability is a hallmark of cancer, and often is the result of altered DNA repair capacities in tumour cells. DNA damage repair defects are common in different cancer types; these alterations can also induce ...
    • Dissecting PARP inhibitor resistance with functional genomics. 

      Pettitt, SJ; Lord, CJ (2019-02)
      The poly-(ADP-ribose) polymerase (PARP) inhibitor (PARPi) olaparib was the first licenced cancer drug that targeted an inherited form of cancer, namely ovarian cancers caused by germline BRCA1 or BRCA2 gene mutations. ...
    • Diverse BRCA1 and BRCA2 Reversion Mutations in Circulating Cell-Free DNA of Therapy-Resistant Breast or Ovarian Cancer. 

      Weigelt, B; Comino-Méndez, I; de Bruijn, I; Tian, L; Meisel, JL; García-Murillas, I; Fribbens, C; Cutts, R; Martelotto, LG; Ng, CKY; Lim, RS; Selenica, P; Piscuoglio, S; Aghajanian, C; Norton, L; Murali, R; Hyman, DM; Borsu, L; Arcila, ME; Konner, J; Reis-Filho, JS; Greenberg, RA; Robson, ME; Turner, NC (2017-11)
      Purpose: Resistance to platinum-based chemotherapy or PARP inhibition in germline BRCA1 or BRCA2 mutation carriers may occur through somatic reversion mutations or intragenic deletions that restore BRCA1 or BRCA2 function. ...
    • DNA Repair in Prostate Cancer: Biology and Clinical Implications. 

      Mateo, J; Boysen, G; Barbieri, CE; Bryant, HE; Castro, E; Nelson, PS; Olmos, D; Pritchard, CC; Rubin, MA; de Bono, JS (2017-03)
      CONTEXT:For more precise, personalized care in prostate cancer (PC), a new classification based on molecular features relevant for prognostication and treatment stratification is needed. Genomic aberrations in the DNA ...
    • Evaluation of Cancer-Based Criteria for Use in Mainstream BRCA1 and BRCA2 Genetic Testing in Patients With Breast Cancer. 

      Kemp, Z; Turnbull, A; Yost, S; Seal, S; Mahamdallie, S; Poyastro-Pearson, E; Warren-Perry, M; Eccleston, A; Tan, M-M; Teo, SH; Turner, N; Strydom, A; George, A; Rahman, N (2019-05-03)
      Importance:Increasing BRCA1 and BRCA2 (collectively termed herein as BRCA) gene testing is required to improve cancer management and prevent BRCA-related cancers. Objective:To evaluate mainstream genetic testing using ...
    • An evaluation of the challenges to developing tumor BRCA1 and BRCA2 testing methodologies for clinical practice. 

      Ellison, G; Ahdesmäki, M; Luke, S; Waring, PM; Wallace, A; Wright, R; Röthlisberger, B; Ludin, K; Merkelbach-Bruse, S; Heydt, C; Ligtenberg, MJL; Mensenkamp, AR; de Castro, DG; Jones, T; Vivancos, A; Kondrashova, O; Pauwels, P; Weyn, C; Hahnen, E; Hauke, J; Soong, R; Lai, Z; Dougherty, B; Carr, TH; Johnson, J; Mills, J; Barrett, JC (2018-03)
      Ovarian cancer patients with germline or somatic pathogenic variants benefit from treatment with poly ADP ribose polymerase (PARP) inhibitors. Tumor BRCA1/2 testing is more challenging than germline testing as the majority ...
    • EXD2 Protects Stressed Replication Forks and Is Required for Cell Viability in the Absence of BRCA1/2. 

      Nieminuszczy, J; Broderick, R; Bellani, MA; Smethurst, E; Schwab, RA; Cherdyntseva, V; Evmorfopoulou, T; Lin, Y-L; Minczuk, M; Pasero, P; Gagos, S; Seidman, MM; Niedzwiedz, W (2019-08)
      Accurate DNA replication is essential to preserve genomic integrity and prevent chromosomal instability-associated diseases including cancer. Key to this process is the cells' ability to stabilize and restart stalled ...
    • Gene and pathway level analyses of germline DNA-repair gene variants and prostate cancer susceptibility using the iCOGS-genotyping array. 

      Saunders, EJ; Dadaev, T; Leongamornlert, DA; Al Olama, AA; Benlloch, S; Giles, GG; Wiklund, F; Gronberg, H; Haiman, CA; Schleutker, J; Nordestgaard, BG; Travis, RC; Neal, D; Pasayan, N; Khaw, K-T; Stanford, JL; Blot, WJ; Thibodeau, SN; Maier, C; Kibel, AS; Cybulski, C; Cannon-Albright, L; Brenner, H; Park, JY; Kaneva, R; Batra, J; Teixeira, MR; Pandha, H; Govindasami, K; Muir, K; UK Genetic Prostate Cancer Study Collaborators; UK ProtecT Study Collaborators; PRACTICAL Consortium; Easton, DF; Eeles, RA; Kote-Jarai, Z (2016-04)
      BACKGROUND:Germline mutations within DNA-repair genes are implicated in susceptibility to multiple forms of cancer. For prostate cancer (PrCa), rare mutations in BRCA2 and BRCA1 give rise to moderately elevated risk, whereas ...
    • 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; Aleksandrov, R; Harrell, MI; Menon, M; Brough, R; Campbell, J; Frankum, J; Ranes, M; Pemberton, HN; Rafiq, R; Fenwick, K; Swain, A; Guettler, S; Lee, J-M; Swisher, EM; Stoynov, S; Yusa, K; Ashworth, A; Lord, CJ (2018-05-10)
      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 ...
    • Genomic alterations in breast cancer: level of evidence for actionability according to ESMO Scale for Clinical Actionability of molecular Targets (ESCAT). 

      Condorelli, R; Mosele, F; Verret, B; Bachelot, T; Bedard, PL; Cortes, J; Hyman, DM; Juric, D; Krop, I; Bieche, I; Saura, C; Sotiriou, C; Cardoso, F; Loibl, S; Andre, F; Turner, NC (2019-03)
      Better knowledge of the tumor genomic landscapes has helped to develop more effective targeted drugs. However, there is no tool to interpret targetability of genomic alterations assessed by next-generation sequencing in ...
    • Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients. 

      Capoluongo, E; Ellison, G; López-Guerrero, JA; Penault-Llorca, F; Ligtenberg, MJL; Banerjee, S; Singer, C; Friedman, E; Markiefka, B; Schirmacher, P; Büttner, R; van Asperen, CJ; Ray-Coquard, I; Endris, V; Kamel-Reid, S; Percival, N; Bryce, J; Röthlisberger, B; Soong, R; de Castro, DG (2017-06)
      The approval, in 2015, of the first poly (adenosine diphosphate-ribose) polymerase inhibitor (PARPi; olaparib, Lynparza) for platinum-sensitive relapsed high-grade ovarian cancer with either germline or somatic BRCA1/2 ...