• Suboptimal T-cell Therapy Drives a Tumor Cell Mutator Phenotype That Promotes Escape from First-Line Treatment. 

  Evgin, L; Huff, AL; Kottke, T; Thompson, J; Molan, AM; Driscoll, CB; Schuelke, M; Shim, KG; Wongthida, P; Ilett, EJ; Smith, KK; Harris, RS; Coffey, M; Pulido, JS; Pandha, H; Selby, PJ; Harrington, KJ; Melcher, A; Vile, RG

  Antitumor T-cell responses raised by first-line therapies such as chemotherapy, radiation, tumor cell vaccines, and viroimmunotherapy tend to be weak, both quantitatively (low frequency) and qualitatively (low affinity). ...
• Potentiating Oncolytic Virus-Induced Immune-Mediated Tumor Cell Killing Using Histone Deacetylase Inhibition. 

  Jennings, VA; Scott, GB; Rose, AMS; Scott, KJ; Migneco, G; Keller, B; Reilly, K; Donnelly, O; Peach, H; Dewar, D; Harrington, KJ; Pandha, H; Samson, A; Vile, RG; Melcher, AA; Errington-Mais, F (2019-06-05)

  A clinical oncolytic herpes simplex virus (HSV) encoding granulocyte-macrophage colony-stimulating factor (GM-CSF), talimogene laherparepvec, causes regression of injected and non-injected melanoma lesions in patients and ...
• Principal component analysis fosr fast and model-free denoising of multi b-value diffusion-weighted MR images. 

  Gurney-Champion, OJ; Collins, DJ; Wetscherek, A; Rata, M; Klaassen, R; van Laarhoven, HWM; Harrington, KJ; Oelfke, U; Orton, MR (2019-05-17)

  Despite the utility of tumour characterisation using quantitative parameter maps from multi-b-value diffusion-weighted MRI (DWI), clinicians often prefer the use of the image with highest diffusion-weighting (b-value), for ...
• Utility of Multi-Parametric Quantitative Magnetic Resonance Imaging for Characterization and Radiotherapy Response Assessment in Soft-Tissue Sarcomas and Correlation With Histopathology. 

  Winfield, JM; Miah, AB; Strauss, D; Thway, K; Collins, DJ; deSouza, NM; Leach, MO; Morgan, VA; Giles, SL; Moskovic, E; Hayes, A; Smith, M; Zaidi, SH; Henderson, D; Messiou, C (2019)

  Purpose: To evaluate repeatability of quantitative multi-parametric MRI in retroperitoneal sarcomas, assess parameter changes with radiotherapy, and correlate pre-operative values with histopathological findings in the ...
• CEA expression heterogeneity and plasticity confer resistance to the CEA-targeting bispecific immunotherapy antibody cibisatamab (CEA-TCB) in patient-derived colorectal cancer organoids. 

  Gonzalez-Exposito, R; Semiannikova, M; Griffiths, B; Khan, K; Barber, LJ; Woolston, A; Spain, G; von Loga, K; Challoner, B; Patel, R; Ranes, M; Swain, A; Thomas, J; Bryant, A; Saffery, C; Fotiadis, N; Guettler, S; Mansfield, D; Melcher, A; Powles, T; Rao, S; Watkins, D; Chau, I; Matthews, N; Wallberg, F; Starling, N; Cunningham, D; Gerlinger, M (2019-04-15)

  BACKGROUND: The T cell bispecific antibody cibisatamab (CEA-TCB) binds Carcino-Embryonic Antigen (CEA) on cancer cells and CD3 on T cells, which triggers T cell killing of cancer cell lines expressing moderate to high ...
• Circulating tumour DNA is a potential biomarker for disease progression and response to targeted therapy in advanced thyroid cancer. 

  Allin, DM; Shaikh, R; Carter, P; Thway, K; Sharabiani, MTA; Gonzales-de-Castro, D; O'Leary, B; Garcia-Murillas, I; Bhide, S; Hubank, M; Harrington, K; Kim, D; Newbold, K (2018-11)

  BACKGROUND: Conventional biomarkers in thyroid cancer are not disease specific and fluctuate in advanced disease, making interpretation difficult. Circulating tumour DNA (ctDNA) has been shown to be a useful biomarker in ...
• Radiotherapy enhances responses of lung cancer to CTLA-4 blockade. 

  Wilkins, A; McDonald, F; Harrington, K; Melcher, A (2019-03-06)

  Formenti et al. have recently reported the clinical outcomes and translational readouts of a trial of the anti-CTLA-4 inhibitor, ipilimumab, in combination with palliative radiotherapy in 39 patients with non-small cell ...
• PD-1 Blockade Following Isolated Limb Perfusion with Vaccinia Virus Prevents Local and Distant Relapse of Soft-tissue Sarcoma. 

  Smith, HG; Mansfield, D; Roulstone, V; Kyula-Currie, JN; McLaughlin, M; Patel, RR; Bergerhoff, KF; Paget, JT; Dillon, MT; Khan, A; Melcher, A; Thway, K; Harrington, KJ; Hayes, AJ (2019-06-01)

  PURPOSE: The prevention and treatment of metastatic sarcoma are areas of significant unmet need. Immune checkpoint inhibitor monotherapy has shown little activity in sarcoma and there is great interest in identifying novel ...
• Targeting EGFR exon 20 insertion mutations in non-small cell lung cancer. 

  Vyse, S; Huang, PH (2019)

  Inframe insertions of three or more base pairs in exon 20 of the epidermal growth factor receptor (EGFR) gene were among the first EGFR mutations to be identified as oncogenic drivers in non-small cell lung cancer (NSCLC). ...
• Mechanical and Systems Biology of Cancer. 

  Spill, F; Bakal, C; Mak, M (2018)

  Mechanics and biochemical signaling are both often deregulated in cancer, leading toincreased cell invasiveness, proliferation, and survival. The dynamics and interactions of cytoskeletal components control basic mechanical ...
• Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses. 

  Helassa, N; Dürst, CD; Coates, C; Kerruth, S; Arif, U; Schulze, C; Wiegert, JS; Geeves, M; Oertner, TG; Török, K (2018-05-22)

  Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of ...
• Phosphoinositide 3-Kinase/Akt Signaling and Redox Metabolism in Cancer. 

  Koundouros, N; Poulogiannis, G (2018)

  Metabolic rewiring and the consequent production of reactive oxygen species (ROS) are necessary to promote tumorigenesis. At the nexus of these cellular processes is the aberrant regulation of oncogenic signaling cascades ...
• De novo mutations implicate novel genes in systemic lupus erythematosus. 

  Pullabhatla, V; Roberts, AL; Lewis, MJ; Mauro, D; Morris, DL; Odhams, CA; Tombleson, P; Liljedahl, U; Vyse, S; Simpson, MA; Sauer, S; de Rinaldis, E; Syvänen, A-C; Vyse, TJ (2018-02-01)

  The omnigenic model of complex disease stipulates that the majority of the heritability will be explained by the effects of common variation on genes in the periphery of core disease pathways. Rare variant associations, ...
• Disruption of the Interaction of RAS with PI 3-Kinase Induces Regression of EGFR-Mutant-Driven Lung Cancer. 

  Murillo, MM; Rana, S; Spencer-Dene, B; Nye, E; Stamp, G; Downward, J (2018-12-26)

  RAS family GTPases contribute directly to the regulation of type I phosphoinositide 3-kinases (PI3Ks) via RAS-binding domains in the PI3K catalytic p110 subunits. Disruption of this domain of p110α impairs RAS-mutant-onc ...
• Repression of Transcription at DNA Breaks Requires Cohesin throughout Interphase and Prevents Genome Instability. 

  Meisenberg, C; Pinder, SI; Hopkins, SR; Wooller, SK; Benstead-Hume, G; Pearl, FMG; Jeggo, PA; Downs, JA (2019-01-17)

  Cohesin subunits are frequently mutated in cancer, but how they function as tumor suppressors is unknown. Cohesin mediates sister chromatid cohesion, but this is not always perturbed in cancer cells. Here, we identify a ...
• Magnetic Resonance-based Response Assessment and Dose Adaptation in Human Papilloma Virus Positive Tumors of the Oropharynx treated with Radiotherapy (MR-ADAPTOR): An R-IDEAL stage 2a-2b/Bayesian phase II trial. 

  Bahig, H; Yuan, Y; Mohamed, ASR; Brock, KK; Ng, SP; Wang, J; Ding, Y; Hutcheson, K; McCulloch, M; Balter, PA; Lai, SY; Al-Mamgani, A; Sonke, J-J; van der Heide, UA; Nutting, C; Li, XA; Robbins, J; Awan, M; Karam, I; Newbold, K; Harrington, K; Oelfke, U; Bhide, S; Philippens, MEP; Terhaard, CHJ; McPartlin, AJ; Blanchard, P; Garden, AS; Rosenthal, DI; Gunn, GB; Phan, J; Cazoulat, G; Aristophanous, M; McSpadden, KK; Garcia, JA; van den Berg, CAT; Raaijmakers, CPJ; Kerkmeijer, L; Doornaert, P; Blinde, S; Frank, SJ; Fuller, CD (2018-11)

  Background: Current standard radiotherapy for oropharynx cancer (OPC) is associated with high rates of severe toxicities, shown to adversely impact patients' quality of life. Given excellent outcomes of human papilloma ...
• Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT). 

  Marabelle, A; Andtbacka, R; Harrington, K; Melero, I; Leidner, R; de Baere, T; Robert, C; Ascierto, PA; Baurain, J-F; Imperiale, M; Rahimian, S; Tersago, D; Klumper, E; Hendriks, M; Kumar, R; Stern, M; Öhrling, K; Massacesi, C; Tchakov, I; Tse, A; Douillard, J-Y; Tabernero, J; Haanen, J; Brody, J (2018-11-01)

  A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were ...
• Ultrahigh Dose-rate Radiotherapy: Next Steps for FLASH-RT. 

  Harrington, KJ (2019-01-01)

  A new way of delivering radiotherapy at very high dose rates is described and compared with conventional radiotherapy. The ultrahigh dose-rate therapy reduces damage to normal pig skin and exerts potent activity against ...
• CheckMate 141: 1-Year Update and Subgroup Analysis of Nivolumab as First-Line Therapy in Patients with Recurrent/Metastatic Head and Neck Cancer. 

  Gillison, ML; Blumenschein, G; Fayette, J; Guigay, J; Colevas, AD; Licitra, L; Harrington, KJ; Kasper, S; Vokes, EE; Even, C; Worden, F; Saba, NF; Iglesias Docampo, LC; Haddad, R; Rordorf, T; Kiyota, N; Tahara, M; Monga, M; Lynch, M; Li, L; Ferris, RL (2018-09)

  Nivolumab significantly improved overall survival (OS) vs investigator's choice (IC) of chemotherapy at the primary analysis of randomized, open-label, phase 3 CheckMate 141 in patients with recurrent or metastatic (R/M) ...
• The immunological consequences of radiation-induced DNA damage. 

  Wilkins, AC; Patin, EC; Harrington, KJ; Melcher, AA (2019-04)

  Historically, our understanding of the cytotoxicity of radiation has centred on tumour cell-autonomous mechanisms of cell death. Here, tumour cell death occurs when a threshold number of radiation-induced non-reparable ...

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