• Leveraging Genome and Phenome-Wide Association Studies to Investigate Genetic Risk of Acute Lymphoblastic Leukemia. 

  Semmes, EC; Vijayakrishnan, J; Zhang, C; Hurst, JH; Houlston, RS; Walsh, KM (2020-05-28)

  BACKGROUND:Genome-wide association studies (GWAS) of childhood cancers remain limited, highlighting the need for novel analytic strategies. We describe a hybrid GWAS and phenome-wide association study (PheWAS) approach to ...
• A mouse SWATH-MS reference spectral library enables deconvolution of species-specific proteomic alterations in human tumour xenografts. 

  Krasny, L; Bland, P; Burns, J; Lima, NC; Harrison, PT; Pacini, L; Elms, ML; Ning, J; Garcia Martinez, V; Yu, Y-R; Acton, SE; Ho, P-C; Calvo, F; Swain, A; Howard, BA; Natrajan, RC; Huang, PH (2020-06-03)

  SWATH-mass spectrometry (MS) enables accurate and reproducible proteomic profiling in multiple model organisms including the mouse. Here we present a comprehensive mouse reference spectral library (MouseRefSWATH) that ...
• Lenalidomide before and after ASCT for transplant-eligible patients of all ages in the randomized, phase III, Myeloma XI trial. 

  Jackson, GH; Davies, FE; Pawlyn, C; Cairns, DA; Striha, A; Collett, C; Waterhouse, A; Jones, JR; Kishore, B; Garg, M; Williams, CD; Karunanithi, K; Lindsay, J; Allotey, D; Shafeek, S; Jenner, MW; Cook, G; Russell, NH; Kaiser, MF; Drayson, MT; Owen, RG; Gregory, WM; Morgan, GJ; UK NCRI Haematological Oncology Clinical Studies Group (2020-06-04)

  The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients ...
• Real-world assessment of the clinical impact of symptomatic infection with severe acute respiratory syndrome coronavirus (COVID-19 disease) in patients with multiple myeloma receiving systemic anti-cancer therapy. 

  Cook, G; John Ashcroft, A; Pratt, G; Popat, R; Ramasamy, K; Kaiser, M; Jenner, M; Henshaw, S; Hall, R; Sive, J; Stern, S; Streetly, M; Bygrave, C; Soutar, R; Rabin, N; Jackson, GH; United Kingdom Myeloma Forum (2020-05-21)
• Tropomyosin receptor kinase inhibitors in the management of sarcomas. 

  Wilding, CP; Loong, HH; Huang, PH; Jones, RL (2020-07)

  PURPOSE OF REVIEW:Genetic aberrations resulting in tropomyosin receptor kinase (TRK) fusion proteins can drive oncogenesis and are postulated to occur in up to 1% of solid tumours. However, TRK fusions in adult sarcomas ...
• Phase I Trial of First-in-Class ATR Inhibitor M6620 (VX-970) as Monotherapy or in Combination With Carboplatin in Patients With Advanced Solid Tumors. 

  Yap, TA; O'Carrigan, B; Penney, MS; Lim, JS; Brown, JS; de Miguel Luken, MJ; Tunariu, N; Perez-Lopez, R; Rodrigues, DN; Riisnaes, R; Figueiredo, I; Carreira, S; Hare, B; McDermott, K; Khalique, S; Williamson, CT; Natrajan, R; Pettitt, SJ; Lord, CJ; Banerji, U; Pollard, J; Lopez, J; de Bono, JS (2020-06-22)

  PURPOSE:Preclinical studies demonstrated that ATR inhibition can exploit synthetic lethality (eg, in cancer cells with impaired compensatory DNA damage responses through ATM loss) as monotherapy and combined with DNA-damaging ...
• Development and validation of the gene-expression Predictor of high-grade-serous Ovarian carcinoma molecular subTYPE (PrOTYPE). 

  Talhouk, A; George, J; Wang, C; Budden, T; Tan, TZ; Chiu, DS; Kommoss, S; Leong, HS; Chen, S; Intermaggio, MP; Gilks, B; Nazeran, TM; Volchek, M; Elatre, W; Bentley, RC; Senz, J; Lum, A; Chow, V; Sudderuddin, H; Mackenzie, R; Leung, S; Liu, G; Johnson, D; Chen, B; Ovarian Cancer Study, A; Alsop, J; Banerjee, S; Behrens, S; Bodelon, C; Brand, AH; Brinton, LA; Carney, ME; Chiew, Y-E; Cushing-Haugen, KL; Cybulski, C; Ennis, D; Fereday, S; Fortner, RT; García-Donás, J; Gentry-Maharaj, A; Glasspool, R; Goranova, T; Greene, CS; Haluska, P; Harris, HR; Hendley, J; Hernandez, BY; Herpel, E; Jimenez-Linan, M; Karpinskyj, C; Kaufmann, SH; Keeney, G; Kennedy, CJ; Köbel, M; Koziak, J; Larson, MC; Lester, J; Lewsley, L-A; Lissowska, J; Lubiński, J; Luk, H; Macintyre, G; Mahner, S; McNeish, IA; Menkiszak, J; Nevins, N; Osorio, A; Oszurek, O; Palacios, J; Hinsley, S; Pearce, CL; Pike, MC; Piskorz, A; Ray-Coquard, I; Rhenius, V; Rodríguez-Antona, C; Sharma, R; Sherman, ME; Silva, D; Singh, N; Sinn, H-P; Slamon, DJ; Song, H; Steed, H; Stronach, EA; Thompson, PJ; Tołoczko-Grabarek, A; Trabert, B; Traficante, N; Tseng, C-C; Widschwendter, M; Wilkens, LR; Winham, SJ; Winterhoff, BJ; Beeghly-Fadiel, A; Benitez, J; Berchuck, A; Brenton, JD; Brown, R; Chang-Claude, J; Chenevix-Trench, G; DeFazio, A; Fasching, PA; Garcia, MJ; Gayther, SA; Goodman, MT; Gronwald, J; Henderson, MJ; Karlan, BY; Kelemen, LE; Menon, U; Orsulic, S; Pharoah, PDP; Wentzensen, N; Wu, AH; Shildkraut, J; Rossing, MA; Konecny, GE; Huntsman, DG; Huang, RY-J; Goode, EL; Ramus, SJ; Doherty, JA; Bowtell, DDL; Anglesio, MS (2020-06-17)

  PURPOSE:Gene-expression-based molecular subtypes of high-grade serous tubo-ovarian cancer (HGSOC), demonstrated across multiple studies, may provide improved stratification for molecularly targeted trials. However, evaluation ...
• ESR1 mutations and overall survival on fulvestrant versus exemestane in advanced hormone receptor positive breast cancer: A combined analysis of the phase III SoFEA and EFECT trials. 

  Turner, NC; Swift, C; Kilburn, LS; Fribbens, C; Beaney, M; Garcia-Murillas, I; Buzdar, AU; Roberston, JF; Gradishar, W; Piccart, M; Schiavon, G; Bliss, JM; Dowsett, M; Johnston, SRD; Chia, SK (2020-06-16)

  PURPOSE:ESR1 mutations are acquired frequently in hormone receptor positive (HR+) metastatic breast cancer after prior aromatase inhibitors (AI). We assessed the clinical utility of baseline ESR1 circulating tumor DNA ...
• Prognostic Value of EndoPredict in Women with Hormone Receptor Positive, HER2-Negative Invasive Lobular Breast Cancer. 

  Sestak, I; Filipits, M; Buus, R; Rudas, M; Balic, M; Knauer, M; Kronenwett, R; Fitzal, F; Cuzick, J; Gnant, M; Greil, R; Dowsett, M; Dubsky, P (2020-06-19)

  PURPOSE:Invasive lobular carcinoma (ILC) accounts for approximately 5-15% of all invasive breast cancer cases. Most of the correlations between multigene assays and patient outcome were derived from studies based on patients ...
• Avapritinib in the treatment of PDGFRA exon 18 mutated gastrointestinal stromal tumors. 

  Smrke, A; Gennatas, S; Huang, P; Jones, RL (2020-06-10)

  Gastrointestinal stromal tumors (GIST) can be molecularly classified based on different subtypes including mutations in KIT and PDGFRA. Patients with PDGFRA mutations are an important subgroup that commonly arise in the ...
• Early relapse after high-dose melphalan autologous stem cell transplant predicts inferior survival and is associated with high disease burden and genetically high-risk disease in multiple myeloma. 

  Bygrave, C; Pawlyn, C; Davies, F; Craig, Z; Cairns, D; Hockaday, A; Jenner, M; Cook, G; Drayson, M; Owen, R; Gregory, W; Morgan, G; Jackson, G; Kaiser, M (2020-06-10)

  Predicting patient outcome in multiple myeloma remains challenging despite the availability of standard prognostic biomarkers. We investigated outcome for patients relapsing early from intensive therapy on NCRI Myeloma XI. ...
• Evidence-based guidelines for managing patients with primary ER+ HER2- breast cancer deferred from surgery due to the COVID-19 pandemic. 

  Dowsett, M; Ellis, MJ; Dixon, JM; Gluz, O; Robertson, J; Kates, R; Suman, VJ; Turnbull, AK; Nitz, U; Christgen, M; Kreipe, H; Kuemmel, S; Bliss, JM; Barry, P; Johnston, SR; Jacobs, SA; Ma, CX; Smith, IE; Harbeck, N (2020-01)

  Many patients with ER+ HER2- primary breast cancer are being deferred from surgery to neoadjuvant endocrine therapy (NeoET) during the COVID-19 pandemic. We have collated data from multiple international trials of presurgical ...
• Microenvironmental Heterogeneity Parallels Breast Cancer Progression: A Histology-Genomic Integration Analysis. 

  Natrajan, R; Sailem, H; Mardakheh, FK; Arias Garcia, M; Tape, CJ; Dowsett, M; Bakal, C; Yuan, Y (2016-02-16)

  The intra-tumor diversity of cancer cells is under intense investigation; however, little is known about the heterogeneity of the tumor microenvironment that is key to cancer progression and evolution. We aimed to assess ...
• RAS signalling through PI3-Kinase controls cell migration via modulation of Reelin expression. 

  Castellano, E; Molina-Arcas, M; Krygowska, AA; East, P; Warne, P; Nicol, A; Downward, J (2016-04-13)

  RAS signalling through phosphoinositide 3-kinase (PI3-Kinase) has been shown to have an essential role in tumour initiation and maintenance. RAS also regulates cell motility and tumour invasiveness, but the role of direct ...
• Defining a New Prognostic Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12 Expression and Proportion of Embryonal Carcinoma. 

  Gilbert, DC; Al-Saadi, R; Thway, K; Chandler, I; Berney, D; Gabe, R; Stenning, SP; Sweet, J; Huddart, R; Shipley, JM (2016-03)

  Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late ...
• 8-Substituted Pyrido[3,4-d]pyrimidin-4(3H)-one Derivatives As Potent, Cell Permeable, KDM4 (JMJD2) and KDM5 (JARID1) Histone Lysine Demethylase Inhibitors. 

  Bavetsias, V; Lanigan, RM; Ruda, GF; Atrash, B; McLaughlin, MG; Tumber, A; Mok, NY; Le Bihan, Y-V; Dempster, S; Boxall, KJ; Jeganathan, F; Hatch, SB; Savitsky, P; Velupillai, S; Krojer, T; England, KS; Sejberg, J; Thai, C; Donovan, A; Pal, A; Scozzafava, G; Bennett, JM; Kawamura, A; Johansson, C; Szykowska, A; Gileadi, C; Burgess-Brown, NA; von Delft, F; Oppermann, U; Walters, Z; Shipley, J; Raynaud, FI; Westaway, SM; Prinjha, RK; Fedorov, O; Burke, R; Schofield, CJ; Westwood, IM; Bountra, C; Müller, S; van Montfort, RLM; Brennan, PE; Blagg, J (2016-02)

  We report the discovery of N-substituted 4-(pyridin-2-yl)thiazole-2-amine derivatives and their subsequent optimization, guided by structure-based design, to give 8-(1H-pyrazol-3-yl)pyrido[3,4-d]pyrimidin-4(3H)-ones, a ...
• Tumour-suppression function of KLF12 through regulation of anoikis. 

  Godin-Heymann, N; Brabetz, S; Murillo, MM; Saponaro, M; Santos, CR; Lobley, A; East, P; Chakravarty, P; Matthews, N; Kelly, G; Jordan, S; Castellano, E; Downward, J (2016-06)

  Suppression of detachment-induced cell death, known as anoikis, is an essential step for cancer metastasis to occur. We report here that expression of KLF12, a member of the Kruppel-like family of transcription factors, ...
• Phase I trial of the poly(ADP-ribose) polymerase (PARP) inhibitor olaparib and AKT inhibitor capivasertib in patients with BRCA1/2 and non-BRCA1/2 mutant cancers. 

  Yap, TA; Kristeleit, R; Michalarea, V; Pettitt, SJ; Lim, JSJ; Carreira, S; Roda, D; Miller, R; Riisnaes, R; Miranda, S; Figueiredo, I; Nava Rodrigues, D; Ward, S; Matthews, R; Parmar, M; Turner, A; Tunariu, N; Chopra, N; Gevensleben, H; Turner, NC; Ruddle, R; Raynaud, FI; Decordova, SA; Swales, KE; Finneran, L; Hall, E; Rugman, P; Lindemann, JPO; Foxley, A; Lord, CJ; Banerji, U; Plummer, R; Basu, B; Lopez, JS; Drew, Y; de Bono, JS (2020-06-12)

  Preclinical studies have demonstrated synergy between poly(ADP-ribose) polymerase (PARP) and phosphatidylinositol-3-kinase (PI3K)/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. ...
• Homologous recombination DNA repair deficiency and PARP inhibition activity in primary triple negative breast cancer. 

  Chopra, N; Tovey, H; Pearson, A; Cutts, R; Toms, C; Proszek, P; Hubank, M; Dowsett, M; Dodson, A; Daley, F; Kriplani, D; Gevensleben, H; Davies, HR; Degasperi, A; Roylance, R; Chan, S; Tutt, A; Skene, A; Evans, A; Bliss, JM; Nik-Zainal, S; Turner, NC (2020-05-29)

  Triple negative breast cancer (TNBC) encompasses molecularly different subgroups, with a subgroup harboring evidence of defective homologous recombination (HR) DNA repair. Here, within a phase 2 window clinical trial, RIO ...
• A Novel Statistical Method to Diagnose, Quantify and Correct Batch Effects in Genomic Studies. 

  Nyamundanda, G; Poudel, P; Patil, Y; Sadanandam, A (2017-09-07)

  Genome projects now generate large-scale data often produced at various time points by different laboratories using multiple platforms. This increases the potential for batch effects. Currently there are several batch ...

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