• SHH pathway inhibition is protumourigenic in adamantinomatous craniopharyngioma. 

  Carreno, G; Boult, JKR; Apps, JR; Gonzalez-Meljem, JM; Haston, S; Guiho, R; Stache, C; Danielson, LS; Koers, A; Smith, LS; Virasami, A; Panousopoulos, L; Buchfelder, M; Jacques, TS; Chesler, L; Robinson, S; Martinez-Barbera, JP (2019-01-01)

  Pharmacological inhibition of the sonic hedgehog (SHH) pathway can be beneficial against certain cancers but detrimental in others. Adamantinomatous craniopharyngioma (ACP) is a relevant pituitary tumour, affecting children ...
• Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling. 

  Bright, MD; Clarke, PA; Workman, P; Davies, FE (2018-04)

  Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. ...
• Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases. 

  Clarke, PA; Ortiz-Ruiz, M-J; TePoele, R; Adeniji-Popoola, O; Box, G; Court, W; Czasch, S; El Bawab, S; Esdar, C; Ewan, K; Gowan, S; De Haven Brandon, A; Hewitt, P; Hobbs, SM; Kaufmann, W; Mallinger, A; Raynaud, F; Roe, T; Rohdich, F; Schiemann, K; Simon, S; Schneider, R; Valenti, M; Weigt, S; Blagg, J; Blaukat, A; Dale, TC; Eccles, SA; Hecht, S; Urbahns, K; Workman, P; Wienke, D (2016-12-09)

  Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility ...
• canSAR: update to the cancer translational research and drug discovery knowledgebase. 

  Coker, EA; Mitsopoulos, C; Tym, JE; Komianou, A; Kannas, C; Di Micco, P; Villasclaras Fernandez, E; Ozer, B; Antolin, AA; Workman, P; Al-Lazikani, B (2019-01-08)

  canSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowlegebase. canSAR informs researchers to help solve key bottlenecks in cancer translation and drug ...
• Towards personalized treatment in multiple myeloma based on molecular characteristics. 

  Pawlyn, C; Davies, FE (2018-12-26)

  To date, the choice of therapy for an individual multiple myeloma patient has been based on clinical factors such as age and co-morbidities. The widespread evolution, validation and clinical utilization of molecular ...
• Lenalidomide maintenance versus observation for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre, open-label, randomised, phase 3 trial. 

  Jackson, GH; Davies, FE; Pawlyn, C; Cairns, DA; Striha, A; Collett, C; Hockaday, A; Jones, JR; Kishore, B; Garg, M; Williams, CD; Karunanithi, K; Lindsay, J; Jenner, MW; Cook, G; Russell, NH; Kaiser, MF; Drayson, MT; Owen, RG; Gregory, WM; Morgan, GJ; UK NCRI Haemato-oncology Clinical Studies Group (2019-01)

  BACKGROUND: Patients with multiple myeloma treated with lenalidomide maintenance therapy have improved progression-free survival, primarily following autologous stem-cell transplantation. A beneficial effect of lenalidomide ...
• The genomic landscape of plasma cells in systemic light chain amyloidosis. 

  Boyle, EM; Ashby, C; Wardell, CP; Rowczenio, D; Sachchithanantham, S; Wang, Y; Johnson, SK; Bauer, MA; Weinhold, N; Kaiser, MF; Johnson, DC; Jones, JR; Pawlyn, C; Proszek, P; Schinke, C; Facon, T; Dumontet, C; Davies, FE; Morgan, GJ; Walker, BA; Wechalekar, AD (2018-12-27)
• Loss of heterozygosity as a marker of homologous repair deficiency in multiple myeloma: a role for PARP inhibition? 

  Pawlyn, C; Loehr, A; Ashby, C; Tytarenko, R; Deshpande, S; Sun, J; Fedorchak, K; Mughal, T; Davies, FE; Walker, BA; Morgan, GJ (2018-07)

  PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a ...
• Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

  Mariotti, L; Pollock, K; Guettler, S (2017-12)

  The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
• Regulation of Wnt/β-catenin signalling by tankyrase-dependent poly(ADP-ribosyl)ation and scaffolding. 

  Mariotti, L; Pollock, K; Guettler, S (2017-12)

  The Wnt/β-catenin signalling pathway is pivotal for stem cell function and the control of cellular differentiation, both during embryonic development and tissue homeostasis in adults. Its activity is carefully controlled ...
• Addition of dose-intensified doxorubicin to standard chemotherapy for rhabdomyosarcoma (EpSSG RMS 2005): a multicentre, open-label, randomised controlled, phase 3 trial. 

  Bisogno, G; Jenney, M; Bergeron, C; Gallego Melcón, S; Ferrari, A; Oberlin, O; Carli, M; Stevens, M; Kelsey, A; De Paoli, A; Gaze, MN; Martelli, H; Devalck, C; Merks, JH; Ben-Arush, M; Glosli, H; Chisholm, J; Orbach, D; Minard-Colin, V; De Salvo, GL; European paediatric Soft tissue sarcoma Study Group (2018-08)

  BACKGROUND: Rhabdomyosarcoma is an aggressive tumour that can develop in almost any part of the body. Doxorubicin is an effective drug against rhabdomyosarcoma, but its role in combination with an established multidrug ...
• Privileged Structures and Polypharmacology within and between Protein Families. 

  Meyers, J; Chessum, NEA; Ali, S; Mok, NY; Wilding, B; Pasqua, AE; Rowlands, M; Tucker, MJ; Evans, LE; Rye, CS; O'Fee, L; Le Bihan, Y-V; Burke, R; Carter, M; Workman, P; Blagg, J; Brown, N; van Montfort, RLM; Jones, K; Cheeseman, MD (2018-12-13)

  Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ...
• A multiple myeloma classification system that associates normal B-cell subset phenotypes with prognosis. 

  Bødker, JS; Brøndum, RF; Schmitz, A; Schönherz, AA; Jespersen, DS; Sønderkær, M; Vesteghem, C; Due, H; Nørgaard, CH; Perez-Andres, M; Samur, MK; Davies, F; Walker, B; Pawlyn, C; Kaiser, M; Johnson, D; Bertsch, U; Broyl, A; van Duin, M; Shah, R; Johansen, P; Nørgaard, MA; Samworth, RJ; Sonneveld, P; Goldschmidt, H; Morgan, GJ; Orfao, A; Munshi, N; Johnson, HE; El-Galaly, T; Dybkær, K; Bøgsted, M (2018-09-25)

  Despite the recent progress in treatment of multiple myeloma (MM), it is still an incurable malignant disease, and we are therefore in need of new risk stratification tools that can help us to understand the disease and ...
• Detection of circulating tumour cell clusters in human glioblastoma. 

  Krol, I; Castro-Giner, F; Maurer, M; Gkountela, S; Szczerba, BM; Scherrer, R; Coleman, N; Carreira, S; Bachmann, F; Anderson, S; Engelhardt, M; Lane, H; Evans, TRJ; Plummer, R; Kristeleit, R; Lopez, J; Aceto, N (2018-08)

  Human glioblastoma (GBM) is a highly aggressive, invasive and hypervascularised malignant brain cancer. Individual circulating tumour cells (CTCs) are sporadically found in GBM patients, yet it is unclear whether multicellular ...
• RB1 Heterogeneity in Advanced Metastatic Castration-Resistant Prostate Cancer. 

  Nava Rodrigues, D; Casiraghi, N; Romanel, A; Crespo, M; Miranda, S; Rescigno, P; Figueiredo, I; Riisnaes, R; Carreira, S; Sumanasuriya, S; Gasperini, P; Sharp, A; Mateo, J; Makay, A; McNair, C; Schiewer, M; Knudsen, K; Boysen, G; Demichelis, F; de Bono, JS (2019-01-15)

  PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) is a lethal but clinically heterogeneous disease, with patients having variable benefit from endocrine and cytotoxic treatments. Intrapatient genomic ...
• Discovery of Quinazolines That Activate SOS1-Mediated Nucleotide Exchange on RAS. 

  Abbott, JR; Patel, PA; Howes, JE; Akan, DT; Kennedy, JP; Burns, MC; Browning, CF; Sun, Q; Rossanese, OW; Phan, J; Waterson, AG; Fesik, SW (2018-09-13)

  Proteins in the RAS family are important regulators of cellular signaling and, when mutated, can drive cancer pathogenesis. Despite considerable effort over the last 30 years, RAS proteins have proven to be recalcitrant ...
• To Cycle or Fight-CDK4/6 Inhibitors at the Crossroads of Anticancer Immunity. 

  Ameratunga, M; Kipps, E; Okines, AFC; Lopez, JS (2019-01-01)

  Dysregulation of cell division resulting in aberrant cell proliferation is a key hallmark of cancer, making it a rational and important target for innovative anticancer drug development. Three selective cyclin-dependent ...
• Driving next-generation autophagy researchers towards translation (DRIVE), an international PhD training program on autophagy. 

  Kraft, C; Boya, P; Codogno, P; Elazar, Z; Eskelinen, E-L; Farrés, J; Kirkin, V; Jungbluth, H; Martinez, A; Pless, O; Primard, C; Proikas-Cezanne, T; Simonsen, A; Reggiori, F (2018-09-13)

  The European autophagy consortium Driving next-generation autophagy researchers towards translation (DRIVE) held its kick-off meeting in Groningen on the 14th and 15th of June 2018. This Marie Skłodowska-Curie Early Training ...
• Affibody-based PET imaging to guide EGFR-targeted cancer therapy in head and neck squamous cell cancer models. 

  Burley, TA; Pieve, CD; Martins, CD; Ciobota, DM; Allott, L; Oyen, WJG; Harrington, KJ; Smith, G; Kramer-Marek, G (2018-09-13)

  In head and neck squamous cell carcinoma (HNSCC), the human epidermal growth factor receptor 1 (EGFR) is the dominant signaling molecule among all members of the family. So far, cetuximab is the only approved anti-EGFR mAb ...
• Target-based therapeutic matching of phase I trials in patients with metastatic breast cancer in a tertiary referral centre. 

  O'Carrigan, B; Lim, JSJ; Jalil, A; Harris, SJ; Papadatos-Pastos, D; Banerji, U; Lopez, J; de Bono, JS; Yap, TA (2018-10)

  BACKGROUND: Greater understanding of the molecular classification of breast cancer has permitted the development of rational drug design strategies. In a phase I clinical trial setting, molecular profiling with next-generation ...

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