Now showing items 1-20 of 62

    • Association of programmed death ligand-1 (PD-L1) expression with treatment outcomes in patients with BRAF mutation-positive melanoma treated with vemurafenib or cobimetinib combined with vemurafenib. 

      Wongchenko, MJ; Ribas, A; Dréno, B; Ascierto, PA; McArthur, GA; Gallo, JD; Rooney, IA; Hsu, J; Koeppen, H; Yan, Y; Larkin, J (2018-07)
      The prognostic significance of programmed death ligand-1 (PD-L1) on treatment outcomes in patients receiving BRAF with or without MEK inhibitors is not well understood. This retrospective exploratory analysis evaluated the ...
    • Ataxia Telangiectasia Mutated Protein Loss and Benefit From Oxaliplatin-based Chemotherapy in Colorectal Cancer. 

      Sundar, R; Miranda, S; Rodrigues, DN; Chénard-Poirier, M; Dolling, D; Clarke, M; Figueiredo, I; Bertan, C; Yuan, W; Ferreira, A; Chistova, R; Boysen, G; Perez, DR; Tunariu, N; Mateo, J; Wotherspoon, A; Chau, I; Cunningham, D; Valeri, N; Carreira, S; de Bono, J (2018-12)
      BACKGROUND: Loss of ataxia telangiectasia mutated (ATM), a key protein regulating DNA repair signaling, has been suggested to increase sensitivity to DNA damaging agents. We conducted a study analyzing the loss of ATM ...
    • Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170. 

      Dunning, AM; Michailidou, K; Kuchenbaecker, KB; Thompson, D; French, JD; Beesley, J; Healey, CS; Kar, S; Pooley, KA; Lopez-Knowles, E; Dicks, E; Barrowdale, D; Sinnott-Armstrong, NA; Sallari, RC; Hillman, KM; Kaufmann, S; Sivakumaran, H; Moradi Marjaneh, M; Lee, JS; Hills, M; Jarosz, M; Drury, S; Canisius, S; Bolla, MK; Dennis, J; Wang, Q; Hopper, JL; Southey, MC; Broeks, A; Schmidt, MK; Lophatananon, A; Muir, K; Beckmann, MW; Fasching, PA; Dos-Santos-Silva, I; Peto, J; Sawyer, EJ; Tomlinson, I; Burwinkel, B; Marme, F; Guénel, P; Truong, T; Bojesen, SE; Flyger, H; González-Neira, A; Perez, JI; Anton-Culver, H; Eunjung, L; Arndt, V; Brenner, H; Meindl, A; Schmutzler, RK; Brauch, H; Hamann, U; Aittomäki, K; Blomqvist, C; Ito, H; Matsuo, K; Bogdanova, N; Dörk, T; Lindblom, A; Margolin, S; Kosma, VM; Mannermaa, A; Tseng, CC; Wu, AH; Lambrechts, D; Wildiers, H; Chang-Claude, J; Rudolph, A; Peterlongo, P; Radice, P; Olson, JE; Giles, GG; Milne, RL; Haiman, CA; Henderson, BE; Goldberg, MS; Teo, SH; Yip, CH; Nord, S; Borresen-Dale, AL; Kristensen, V; Long, J; Zheng, W; Pylkäs, K; Winqvist, R; Andrulis, IL; Knight, JA; Devilee, P; Seynaeve, C; Figueroa, J; Sherman, ME; Czene, K; Darabi, H; Hollestelle, A; van den Ouweland, AM; Humphreys, K; Gao, YT; Shu, XO; Cox, A; Cross, SS; Blot, W; Cai, Q; Ghoussaini, M; Perkins, BJ; Shah, M; Choi, JY; Kang, D; Lee, SC; Hartman, M; Kabisch, M; Torres, D; Jakubowska, A; Lubinski, J; Brennan, P; Sangrajrang, S; Ambrosone, CB; Toland, AE; Shen, CY; Wu, PE; Orr, N; Swerdlow, A; McGuffog, L; Healey, S; Lee, A; Kapuscinski, M; John, EM; Terry, MB; Daly, MB; Goldgar, DE; Buys, SS; Janavicius, R; Tihomirova, L; Tung, N; Dorfling, CM; van Rensburg, EJ; Neuhausen, SL; Ejlertsen, B; Hansen, TV; Osorio, A; Benitez, J; Rando, R; Weitzel, JN; Bonanni, B; Peissel, B; Manoukian, S; Papi, L; Ottini, L; Konstantopoulou, I; Apostolou, P; Garber, J; Rashid, MU; Frost, D; Izatt, L; Ellis, S; Godwin, AK; Arnold, N; Niederacher, D; Rhiem, K; Bogdanova-Markov, N; Sagne, C; Stoppa-Lyonnet, D; Damiola, F; Sinilnikova, OM; Mazoyer, S; Isaacs, C; Claes, KB; De Leeneer, K; de la Hoya, M; Caldes, T; Nevanlinna, H; Khan, S; Mensenkamp, AR; Hooning, MJ; Rookus, MA; Kwong, A; Olah, E; Diez, O; Brunet, J; Pujana, MA; Gronwald, J; Huzarski, T; Barkardottir, RB; Laframboise, R; Soucy, P; Montagna, M; Agata, S; Teixeira, MR; Park, SK; Lindor, N; Couch, FJ; Tischkowitz, M; Foretova, L; Vijai, J; Offit, K; Singer, CF; Rappaport, C; Phelan, CM; Greene, MH; Mai, PL; Rennert, G; Imyanitov, EN; Hulick, PJ; Phillips, KA; Piedmonte, M; Mulligan, AM; Glendon, G; Bojesen, A; Thomassen, M; Caligo, MA; Yoon, SY; Friedman, E; Laitman, Y; Borg, A; von Wachenfeldt, A; Ehrencrona, H; Rantala, J; Olopade, OI; Ganz, PA; Nussbaum, RL; Gayther, SA; Nathanson, KL; Domchek, SM; Arun, BK; Mitchell, G; Karlan, BY; Lester, J; Maskarinec, G; Woolcott, C; Scott, C; Stone, J; Apicella, C; Tamimi, R; Luben, R; Khaw, KT; Helland, Å; Haakensen, V; Dowsett, M; Pharoah, PD; Simard, J; Hall, P; García-Closas, M; Vachon, C; Chenevix-Trench, G; Antoniou, AC; Easton, DF; Edwards, SL (2016-04)
      We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each ...
    • Bromodomain protein 4 discriminates tissue-specific super-enhancers containing disease-specific susceptibility loci in prostate and breast cancer. 

      Zuber, V; Bettella, F; Witoelar, A; PRACTICAL Consortium; CRUK GWAS; BCAC Consortium; TRICL Consortium; Andreassen, OA; Mills, IG; Urbanucci, A (2017-03-31)
      BACKGROUND: Epigenetic information can be used to identify clinically relevant genomic variants single nucleotide polymorphisms (SNPs) of functional importance in cancer development. Super-enhancers are cell-specific DNA ...
    • Catch my drift? Making sense of genomic intra-tumour heterogeneity. 

      Sottoriva, A; Barnes, CP; Graham, TA (2017-04)
      The cancer genome is shaped by three components of the evolutionary process: mutation, selection and drift. While many studies have focused on the first two components, the role of drift in cancer evolution has received ...
    • Cdc42 regulates Cdc42EP3 function in cancer-associated fibroblasts. 

      Farrugia, AJ; Calvo, F (2017-01-02)
      Rho family GTPases such as Cdc42 are key regulators of essential cellular processes through their effects on cytoskeletal dynamics, signaling and gene expression. Rho GTPases modulate these functions by engaging a wide ...
    • 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 ...
    • Characterisation of the immune-related transcriptome in resected biliary tract cancers. 

      Ghidini, M; Cascione, L; Carotenuto, P; Lampis, A; Trevisani, F; Previdi, MC; Hahne, JC; Said-Huntingford, I; Raj, M; Zerbi, A; Mescoli, C; Cillo, U; Rugge, M; Roncalli, M; Torzilli, G; Rimassa, L; Santoro, A; Valeri, N; Fassan, M; Braconi, C (2017-11)
      Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling ...
    • Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast. 

      Natrajan, R; Wilkerson, PM; Marchiò, C; Piscuoglio, S; Ng, CK; 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 ...
    • CHD1 loss sensitizes prostate cancer to DNA damaging therapy by promoting error-prone double-strand break repair. 

      Shenoy, TR; Boysen, G; Wang, MY; Xu, QZ; Guo, W; Koh, FM; Wang, C; Zhang, LZ; Wang, Y; Gil, V; Aziz, S; Christova, R; Rodrigues, DN; Crespo, M; Rescigno, P; Tunariu, N; Riisnaes, R; Zafeiriou, Z; Flohr, P; Yuan, W; Knight, E; Swain, A; Ramalho-Santos, M; Xu, DY; de Bono, J; Wu, H (2017-07-01)
      Background: Deletion of the chromatin remodeler chromodomain helicase DNA-binding protein 1 (CHD1) is a common genomic alteration found in human prostate cancers (PCas). CHD1 loss represents a distinct PCa subtype characterized ...
    • A Compendium of Co-regulated Protein Complexes in Breast Cancer Reveals Collateral Loss Events. 

      Ryan, CJ; Kennedy, S; Bajrami, I; Matallanas, D; Lord, CJ (2017-10-25)
      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 ...
    • Cyclin-Dependent Kinase Inhibitor AT7519 as a Potential Drug for MYCN-Dependent Neuroblastoma. 

      Dolman, ME; Poon, E; Ebus, ME; den Hartog, IJ; van Noesel, CJ; Jamin, Y; Hallsworth, A; Robinson, SP; Petrie, K; Sparidans, RW; Kok, RJ; Versteeg, R; Caron, HN; Chesler, L; Molenaar, JJ (2015-11)
      MYCN-dependent neuroblastomas have low cure rates with current multimodal treatment regimens and novel therapeutic drugs are therefore urgently needed. In previous preclinical studies, we have shown that targeted inhibition ...
    • Deregulated expression of HDAC9 in B cells promotes development of lymphoproliferative disease and lymphoma in mice. 

      Gil, VS; Bhagat, G; Howell, L; Zhang, J; Kim, CH; Stengel, S; Vega, F; Zelent, A; Petrie, K (2016-12-01)
      Histone deacetylase 9 (HDAC9) is expressed in B cells, and its overexpression has been observed in B-lymphoproliferative disorders, including B-cell non-Hodgkin lymphoma (B-NHL). We examined HDAC9 protein expression and ...
    • EGFR feedback-inhibition by Ran-binding protein 6 is disrupted in cancer. 

      Oldrini, B; Hsieh, W-Y; Erdjument-Bromage, H; Codega, P; Carro, MS; Curiel-García, A; Campos, C; Pourmaleki, M; Grommes, C; Vivanco, I; Rohle, D; Bielski, CM; Taylor, BS; Hollmann, TJ; Rosenblum, M; Tempst, P; Blenis, J; Squatrito, M; Mellinghoff, IK (2017-12-11)
      Transport of macromolecules through the nuclear pore by importins and exportins plays a critical role in the spatial regulation of protein activity. How cancer cells co-opt this process to promote tumorigenesis remains ...
    • Elevated APOBEC3B expression drives a kataegic-like mutation signature and replication stress-related therapeutic vulnerabilities in p53-defective cells. 

      Nikkilä, J; Kumar, R; Campbell, J; Brandsma, I; Pemberton, HN; Wallberg, F; Nagy, K; Scheer, I; Vertessy, BG; Serebrenik, AA; Monni, V; Harris, RS; Pettitt, SJ; Ashworth, A; Lord, CJ (2017-06-27)
      BACKGROUND: Elevated APOBEC3B expression in tumours correlates with a kataegic pattern of localised hypermutation. We assessed the cellular phenotypes associated with high-level APOBEC3B expression and the influence of p53 ...
    • Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy. 

      Xiao, T; Li, W; Wang, X; Xu, H; Yang, J; Wu, Q; Huang, Y; Geradts, J; Jiang, P; Fei, T; Chi, D; Zang, C; Liao, Q; Rennhack, J; Andrechek, E; Li, N; Detre, S; Dowsett, M; Jeselsohn, RM; Liu, XS; Brown, M (2018-07-31)
      Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical ...
    • Forced mitotic entry of S-phase cells as a therapeutic strategy induced by inhibition of WEE1. 

      Aarts, M; Sharpe, R; Garcia-Murillas, I; Gevensleben, H; Hurd, MS; Shumway, SD; Toniatti, C; Ashworth, A; Turner, NC (2012-06)
      Inhibition of the protein kinase WEE1 synergizes with chemotherapy in preclinical models and WEE1 inhibitors are being explored as potential cancer therapies. Here, we investigate the mechanism that underlies this synergy. ...
    • From integrative genomics to therapeutic targets. 

      Natrajan, R; Wilkerson, P (2013-06-05)
      Combinatorial approaches that integrate conventional pathology with genomic profiling and functional genomics have begun to enhance our understanding of the genetic basis of breast cancer. These methods have identified key ...
    • GDNF-RET signaling in ER-positive breast cancers is a key determinant of response and resistance to aromatase inhibitors. 

      Morandi, A; Martin, LA; Gao, Q; Pancholi, S; Mackay, A; Robertson, D; Zvelebil, M; Dowsett, M; Plaza-Menacho, I; Isacke, CM (2013-06)
      Most breast cancers at diagnosis are estrogen receptor-positive (ER(+)) and depend on estrogen for growth and survival. Blocking estrogen biosynthesis by aromatase inhibitors has therefore become a first-line endocrine ...