Now showing items 1-20 of 23

    • 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 ...
    • The clinical development candidate CCT245737 is an orally active CHK1 inhibitor with preclinical activity in RAS mutant NSCLC and Eµ-MYC driven B-cell lymphoma. 

      Walton, MI; Eve, PD; Hayes, A; Henley, AT; Valenti, MR; De Haven Brandon, AK; Box, G; Boxall, KJ; Tall, M; Swales, K; Matthews, TP; McHardy, T; Lainchbury, M; Osborne, J; Hunter, JE; Perkins, ND; Aherne, GW; Reader, JC; Raynaud, FI; Eccles, SA; Collins, I; Garrett, MD (2016-01)
      CCT245737 is the first orally active, clinical development candidate CHK1 inhibitor to be described. The IC50 was 1.4 nM against CHK1 enzyme and it exhibited>1,000-fold selectivity against CHK2 and CDK1. CCT245737 potently ...
    • Clinical outcomes of adolescents and young adults with advanced solid tumours participating in phase I trials. 

      Sundar, R; McVeigh, T; Dolling, D; Petruckevitch, A; Diamantis, N; Ang, JE; Chenard-Poiriér, M; Collins, D; Lim, J; Ameratunga, M; Khan, K; Kaye, SB; Banerji, U; Lopez, J; George, AJ; de Bono, JS; van der Graaf, WT (2018-09)
      BACKGROUND:Adolescent and young adult (AYA) patients with advanced solid tumours are often considered for phase I clinical trials with novel agents. The outcome of AYAs in these trials have not been described before. AIM:To ...
    • Dalotuzumab in chemorefractory KRAS exon 2 mutant colorectal cancer: Results from a randomised phase II/III trial. 

      Sclafani, F; Kim, TY; Cunningham, D; Kim, TW; Tabernero, J; Schmoll, HJ; Roh, JK; Kim, SY; Park, YS; Guren, TK; Hawkes, E; Clarke, SJ; Ferry, D; Frodin, J-E; Ayers, M; Nebozhyn, M; Peckitt, C; Loboda, A; Watkins, DJ (2017-01)
      Limited data are available on the efficacy of anti-IGF-1R agents in KRAS mutant colorectal cancer (CRC). We analysed the outcome of 69 chemorefractory, KRAS exon 2 mutant CRC patients who were enrolled in a double-blind, ...
    • Differences in Signaling Patterns on PI3K Inhibition Reveal Context Specificity in KRAS-Mutant Cancers. 

      Stewart, A; Coker, EA; Pölsterl, S; Georgiou, A; Minchom, AR; Carreira, S; Cunningham, D; O'Brien, ME; Raynaud, FI; de Bono, JS; Al-Lazikani, B; Banerji, U (2019-08)
      It is increasingly appreciated that drug response to different cancers driven by the same oncogene is different and may relate to differences in rewiring of signal transduction. We aimed to study differences in dynamic ...
    • Effect of Pathologic Tumor Response and Nodal Status on Survival in the Medical Research Council Adjuvant Gastric Infusional Chemotherapy Trial. 

      Smyth, EC; Fassan, M; Cunningham, D; Allum, WH; Okines, AFC; Lampis, A; Hahne, JC; Rugge, M; Peckitt, C; Nankivell, M; Langley, R; Ghidini, M; Braconi, C; Wotherspoon, A; Grabsch, HI; Valeri, N (2016-08)
      PURPOSE:The Medical Research Council Adjuvant Gastric Infusional Chemotherapy (MAGIC) trial established perioperative epirubicin, cisplatin, and fluorouracil chemotherapy as a standard of care for patients with resectable ...
    • Efficient Genotyping of KRAS Mutant Non-Small Cell Lung Cancer Using a Multiplexed Droplet Digital PCR Approach. 

      Pender, A; Garcia-Murillas, I; Rana, S; Cutts, RJ; Kelly, G; Fenwick, K; Kozarewa, I; Gonzalez de Castro, D; Bhosle, J; O'Brien, M; Turner, NC; Popat, S; Downward, J (2015-01)
      Droplet digital PCR (ddPCR) can be used to detect low frequency mutations in oncogene-driven lung cancer. The range of KRAS point mutations observed in NSCLC necessitates a multiplex approach to efficient mutation detection ...
    • Enhanced cytotoxicity of reovirus and radiotherapy in melanoma cells is mediated through increased viral replication and mitochondrial apoptotic signalling. 

      McEntee, G; Kyula, JN; Mansfield, D; Smith, H; Wilkinson, M; Gregory, C; Roulstone, V; Coffey, M; Harrington, KJ (2016-07)
      Oncolytic viruses selectively target and replicate in cancer cells, providing us with a unique tool with which to target and kill tumour cells. These viruses come from a diverse range of viral families including reovirus ...
    • Gefitinib and EGFR Gene Copy Number Aberrations in Esophageal Cancer. 

      Petty, RD; Dahle-Smith, A; Stevenson, DAJ; Osborne, A; Massie, D; Clark, C; Murray, GI; Dutton, SJ; Roberts, C; Chong, IY; Mansoor, W; Thompson, J; Harrison, M; Chatterjee, A; Falk, SJ; Elyan, S; Garcia-Alonso, A; Fyfe, DW; Wadsley, J; Chau, I; Ferry, DR; Miedzybrodzka, Z (2017-07)
      Purpose The Cancer Esophagus Gefitinib trial demonstrated improved progression-free survival with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor gefitinib relative to placebo in patients with advanced ...
    • Genomic markers of panitumumab resistance including ERBB2/ HER2 in a phase II study of KRAS wild-type (wt) metastatic colorectal cancer (mCRC). 

      Barry, GS; Cheang, MC; Chang, HL; Kennecke, HF (2016-04)
      A prospective study was conducted to identify biomarkers associated with resistance to panitumumab monotherapy in patients with metastatic colorectal cancer (mCRC). Patients with previously treated, codon 12/13 KRAS wt, ...
    • KRAS and BRAF mutations in circulating tumour DNA from locally advanced rectal cancer. 

      Sclafani, F; Chau, I; Cunningham, D; Hahne, JC; Vlachogiannis, G; Eltahir, Z; Lampis, A; Braconi, C; Kalaitzaki, E; De Castro, DG; Wotherspoon, A; Capdevila, J; Glimelius, B; Tarazona, N; Begum, R; Lote, H; Hulkki Wilson, S; Mentrasti, G; Brown, G; Tait, D; Oates, J; Valeri, N (2018-01-23)
      There are limited data on circulating, cell-free, tumour (ct)DNA analysis in locally advanced rectal cancer (LARC). Digital droplet (dd)PCR was used to investigate KRAS/BRAF mutations in ctDNA from baseline blood samples ...
    • KRAS-specific inhibition using a DARPin binding to a site in the allosteric lobe. 

      Bery, N; Legg, S; Debreczeni, J; Breed, J; Embrey, K; Stubbs, C; Kolasinska-Zwierz, P; Barrett, N; Marwood, R; Watson, J; Tart, J; Overman, R; Miller, A; Phillips, C; Minter, R; Rabbitts, TH (2019-06-13)
      Inhibiting the RAS oncogenic protein has largely been through targeting the switch regions that interact with signalling effector proteins. Here, we report designed ankyrin repeat proteins (DARPins) macromolecules that ...
    • The molecular landscape of colitis-associated carcinogenesis. 

      Saraggi, D; Fassan, M; Mescoli, C; Scarpa, M; Valeri, N; Michielan, A; D'Incá, R; Rugge, M (2017-04)
      In spite of the well-established histopathological phenotyping of IBD-associated preneoplastic and neoplastic lesions, their molecular landscape remains to be fully elucidated. Several studies have pinpointed the initiating ...
    • No clinical utility of KRAS variant rs61764370 for ovarian or breast cancer. 

      Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, and Consortium of Modifiers of BRCA1 and BRCA2; Hollestelle, A; van der Baan, FH; Berchuck, A; Johnatty, SE; Aben, KK; Agnarsson, BA; Aittomäki, K; Alducci, E; Andrulis, IL; Anton-Culver, H; Antonenkova, NN; Antoniou, AC; Apicella, C; Arndt, V; Arnold, N; Arun, BK; Arver, B; Ashworth, A; Australian Ovarian Cancer Study Group; Baglietto, L; Balleine, R; Bandera, EV; Barrowdale, D; Bean, YT; Beckmann, L; Beckmann, MW; Benitez, J; Berger, A; Berger, R; Beuselinck, B; Bisogna, M; Bjorge, L; Blomqvist, C; Bogdanova, NV; Bojesen, A; Bojesen, SE; Bolla, MK; Bonanni, B; Brand, JS; Brauch, H; Breast Cancer Family Register; Brenner, H; Brinton, L; Brooks-Wilson, A; Bruinsma, F; Brunet, J; Brüning, T; Budzilowska, A; Bunker, CH; Burwinkel, B; Butzow, R; Buys, SS; Caligo, MA; Campbell, I; Carter, J; Chang-Claude, J; Chanock, SJ; Claes, KBM; Collée, JM; Cook, LS; Couch, FJ; Cox, A; Cramer, D; Cross, SS; Cunningham, JM; Cybulski, C; Czene, K; Damiola, F; Dansonka-Mieszkowska, A; Darabi, H; de la Hoya, M; deFazio, A; Dennis, J; Devilee, P; Dicks, EM; Diez, O; Doherty, JA; Domchek, SM; Dorfling, CM; Dörk, T; Silva, IDS; du Bois, A; Dumont, M; Dunning, AM; Duran, M; Easton, DF; Eccles, D; Edwards, RP; Ehrencrona, H; Ejlertsen, B; Ekici, AB; Ellis, SD; EMBRACE; Engel, C; Eriksson, M; Fasching, PA; Feliubadalo, L; Figueroa, J; Flesch-Janys, D; Fletcher, O; Fontaine, A; Fortuzzi, S; Fostira, F; Fridley, BL; Friebel, T; Friedman, E; Friel, G; Frost, D; Garber, J; García-Closas, M; Gayther, SA; GEMO Study Collaborators; GENICA Network; Gentry-Maharaj, A; Gerdes, A-M; Giles, GG; Glasspool, R; Glendon, G; Godwin, AK; Goodman, MT; Gore, M; Greene, MH; Grip, M; Gronwald, J; Gschwantler Kaulich, D; Guénel, P; Guzman, SR; Haeberle, L; Haiman, CA; Hall, P; Halverson, SL; Hamann, U; Hansen, TVO; Harter, P; Hartikainen, JM; Healey, S; HEBON; Hein, A; Heitz, F; Henderson, BE; Herzog, J; T Hildebrandt, MA; Høgdall, CK; Høgdall, E; Hogervorst, FBL; Hopper, JL; Humphreys, K; Huzarski, T; Imyanitov, EN; Isaacs, C; Jakubowska, A; Janavicius, R; Jaworska, K; Jensen, A; Jensen, UB; Johnson, N; Jukkola-Vuorinen, A; Kabisch, M; Karlan, BY; Kataja, V; Kauff, N; KConFab Investigators; Kelemen, LE; Kerin, MJ; Kiemeney, LA; Kjaer, SK; Knight, JA; Knol-Bout, JP; Konstantopoulou, I; Kosma, V-M; Krakstad, C; Kristensen, V; Kuchenbaecker, KB; Kupryjanczyk, J; Laitman, Y; Lambrechts, D; Lambrechts, S; Larson, MC; Lasa, A; Laurent-Puig, P; Lazaro, C; Le, ND; Le Marchand, L; Leminen, A; Lester, J; Levine, DA; Li, J; Liang, D; Lindblom, A; Lindor, N; Lissowska, J; Long, J; Lu, KH; Lubinski, J; Lundvall, L; Lurie, G; Mai, PL; Mannermaa, A; Margolin, S; Mariette, F; Marme, F; Martens, JWM; Massuger, LFAG; Maugard, C; Mazoyer, S; McGuffog, L; McGuire, V; McLean, C; McNeish, I; Meindl, A; Menegaux, F; Menéndez, P; Menkiszak, J; Menon, U; Mensenkamp, AR; Miller, N; Milne, RL; Modugno, F; Montagna, M; Moysich, KB; Müller, H; Mulligan, AM; Muranen, TA; Narod, SA; Nathanson, KL; Ness, RB; Neuhausen, SL; Nevanlinna, H; Neven, P; Nielsen, FC; Nielsen, SF; Nordestgaard, BG; Nussbaum, RL; Odunsi, K; Offit, K; Olah, E; Olopade, OI; Olson, JE; Olson, SH; Oosterwijk, JC; Orlow, I; Orr, N; Orsulic, S; Osorio, A; Ottini, L; Paul, J; Pearce, CL; Pedersen, IS; Peissel, B; Pejovic, T; Pelttari, LM; Perkins, J; Permuth-Wey, J; Peterlongo, P; Peto, J; Phelan, CM; Phillips, K-A; Piedmonte, M; Pike, MC; Platte, R; Plisiecka-Halasa, J; Poole, EM; Poppe, B; Pylkäs, K; Radice, P; Ramus, SJ; Rebbeck, TR; Reed, MWR; Rennert, G; Risch, HA; Robson, M; Rodriguez, GC; Romero, A; Rossing, MA; Rothstein, JH; Rudolph, A; Runnebaum, I; Salani, R; Salvesen, HB; Sawyer, EJ; Schildkraut, JM; Schmidt, MK; Schmutzler, RK; Schneeweiss, A; Schoemaker, MJ; Schrauder, MG; Schumacher, F; Schwaab, I; Scuvera, G; Sellers, TA; Severi, G; Seynaeve, CM; Shah, M; Shrubsole, M; Siddiqui, N; Sieh, W; Simard, J; Singer, CF; Sinilnikova, OM; Smeets, D; Sohn, C; Soller, M; Song, H; Soucy, P; Southey, MC; Stegmaier, C; Stoppa-Lyonnet, D; Sucheston, L; SWE-BRCA; Swerdlow, A; Tangen, IL; Tea, M-K; Teixeira, MR; Terry, KL; Terry, MB; Thomassen, M; Thompson, PJ; Tihomirova, L; Tischkowitz, M; Toland, AE; Tollenaar, RAEM; Tomlinson, I; Torres, D; Truong, T; Tsimiklis, H; Tung, N; Tworoger, SS; Tyrer, JP; Vachon, CM; Van 't Veer, LJ; van Altena, AM; Van Asperen, CJ; van den Berg, D; van den Ouweland, AMW; van Doorn, HC; Van Nieuwenhuysen, E; van Rensburg, EJ; Vergote, I; Verhoef, S; Vierkant, RA; Vijai, J; Vitonis, AF; von Wachenfeldt, A; Walsh, C; Wang, Q; Wang-Gohrke, S; Wappenschmidt, B; Weischer, M; Weitzel, JN; Weltens, C; Wentzensen, N; Whittemore, AS; Wilkens, LR; Winqvist, R; Wu, AH; Wu, X; Yang, HP; Zaffaroni, D; Pilar Zamora, M; Zheng, W; Ziogas, A; Chenevix-Trench, G; Pharoah, PDP; Rookus, MA; Hooning, MJ; Goode, EL (2016-05)
      OBJECTIVE:Clinical genetic testing is commercially available for rs61764370, an inherited variant residing in a KRAS 3' UTR microRNA binding site, based on suggested associations with increased ovarian and breast cancer ...
    • Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation. 

      Tape, CJ; Ling, S; Dimitriadi, M; McMahon, KM; Worboys, JD; Leong, HS; Norrie, IC; Miller, CJ; Poulogiannis, G; Lauffenburger, DA; Jørgensen, C (2016-05)
      Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRAS(G12D)) also regulates tumor cell signaling via stromal cells. By combining cell-specific ...
    • Oncogenic KRAS sensitizes premalignant, but not malignant cells, to Noxa-dependent apoptosis through the activation of the MEK/ERK pathway. 

      Conti, A; Majorini, MT; Elliott, R; Ashworth, A; Lord, CJ; Cancelliere, C; Bardelli, A; Seneci, P; Walczak, H; Delia, D; Lecis, D (2015-05)
      KRAS is mutated in about 20-25% of all human cancers and especially in pancreatic, lung and colorectal tumors. Oncogenic KRAS stimulates several pro-survival pathways, but it also triggers the trans-activation of pro-apoptotic ...
    • Oncogenic RAS Signaling Promotes Tumor Immunoresistance by Stabilizing PD-L1 mRNA. 

      Coelho, MA; de Carné Trécesson, S; Rana, S; Zecchin, D; Moore, C; Molina-Arcas, M; East, P; Spencer-Dene, B; Nye, E; Barnouin, K; Snijders, AP; Lai, WS; Blackshear, PJ; Downward, J (2017-12-12)
      The immunosuppressive protein PD-L1 is upregulated in many cancers and contributes to evasion of the host immune system. The relative importance of the tumor microenvironment and cancer cell-intrinsic signaling in the ...
    • PKA-regulated VASP phosphorylation promotes extrusion of transformed cells from the epithelium. 

      Anton, KA; Sinclair, J; Ohoka, A; Kajita, M; Ishikawa, S; Benz, PM; Renne, T; Balda, M; Jorgensen, C; Matter, K; Fujita, Y (2014-08)
      At the early stages of carcinogenesis, transformation occurs in single cells within tissues. In an epithelial monolayer, such mutated cells are recognized by their normal neighbors and are often apically extruded. The ...
    • Robust RNA-based in situ mutation detection delineates colorectal cancer subclonal evolution. 

      Baker, A-M; Huang, W; Wang, X-MM; Jansen, M; Ma, X-J; Kim, J; Anderson, CM; Wu, X; Pan, L; Su, N; Luo, Y; Domingo, E; Heide, T; Sottoriva, A; Lewis, A; Beggs, AD; Wright, NA; Rodriguez-Justo, M; Park, E; Tomlinson, I; Graham, TA (2017-12-08)
      Intra-tumor heterogeneity (ITH) is a major underlying cause of therapy resistance and disease recurrence, and is a read-out of tumor growth. Current genetic ITH analysis methods do not preserve spatial context and may not ...
    • Suppression of interferon gene expression overcomes resistance to MEK inhibition in KRAS-mutant colorectal cancer. 

      Wagner, S; Vlachogiannis, G; De Haven Brandon, A; Valenti, M; Box, G; Jenkins, L; Mancusi, C; Self, A; Manodoro, F; Assiotis, I; Robinson, P; Chauhan, R; Rust, AG; Matthews, N; Eason, K; Khan, K; Starling, N; Cunningham, D; Sadanandam, A; Isacke, CM; Kirkin, V; Valeri, N; Whittaker, SR (2019-03)
      Despite showing clinical activity in BRAF-mutant melanoma, the MEK inhibitor (MEKi) trametinib has failed to show clinical benefit in KRAS-mutant colorectal cancer. To identify mechanisms of resistance to MEKi, we employed ...