Now showing items 1-17 of 17

    • Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer. 

      Rafii, S; Gourley, C; Kumar, R; Geuna, E; Ern Ang, J; Rye, T; Chen, L-M; Shapira-Frommer, R; Friedlander, M; Matulonis, U; De Greve, J; Oza, AM; Banerjee, S; Molife, LR; Gore, ME; Kaye, SB; Yap, TA (2017-07)
      Background The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in ...
    • Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials. 

      George, A; Kristeleit, R; Rafii, S; Michie, CO; Bowen, R; Michalarea, V; van Hagen, T; Wong, M; Rallis, G; Molife, LR; Lopez, J; Banerji, U; Banerjee, SN; Gore, ME; de Bono, JS; Kaye, SB; Yap, TA (2017-05)
      Drug resistance to conventional anticancer therapies is almost inevitable in patients with advanced ovarian cancer (AOC), limiting their available treatment options. Novel phase I trial therapies within a dedicated drug ...
    • Contemporary outcomes from the use of regular imaging to detect relapse in high-risk cutaneous melanoma. 

      Lim, KHJ; Spain, L; Barker, C; Georgiou, A; Walls, G; Gore, M; Turajlic, S; Board, R; Larkin, JM; Lorigan, P (2018-01)
      Background:Agreement on the utility of imaging follow-up in patients with high-risk melanoma is lacking. A UK consensus statement recommends a surveillance schedule of CT or positron-emission tomography-CT and MRI brain ...
    • Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. 

      Turajlic, S; Xu, H; Litchfield, K; Rowan, A; Horswell, S; Chambers, T; O'Brien, T; Lopez, JI; Watkins, TBK; Nicol, D; Stares, M; Challacombe, B; Hazell, S; Chandra, A; Mitchell, TJ; Au, L; Eichler-Jonsson, C; Jabbar, F; Soultati, A; Chowdhury, S; Rudman, S; Lynch, J; Fernando, A; Stamp, G; Nye, E; Stewart, A; Xing, W; Smith, JC; Escudero, M; Huffman, A; Matthews, N; Elgar, G; Phillimore, B; Costa, M; Begum, S; Ward, S; Salm, M; Boeing, S; Fisher, R; Spain, L; Navas, C; Grönroos, E; Hobor, S; Sharma, S; Aurangzeb, I; Lall, S; Polson, A; Varia, M; Horsfield, C; Fotiadis, N; Pickering, L; Schwarz, RF; Silva, B; Herrero, J; Luscombe, NM; Jamal-Hanjani, M; Rosenthal, R; Birkbak, NJ; Wilson, GA; Pipek, O; Ribli, D; Krzystanek, M; Csabai, I; Szallasi, Z; Gore, M; McGranahan, N; Van Loo, P; Campbell, P; Larkin, J; Swanton, C; TRACERx Renal Consortium (2018-04-12)
      The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, ...
    • Development of synchronous VHL syndrome tumors reveals contingencies and constraints to tumor evolution. 

      Fisher, R; Horswell, S; Rowan, A; Salm, MP; de Bruin, EC; Gulati, S; McGranahan, N; Stares, M; Gerlinger, M; Varela, I; Crockford, A; Favero, F; Quidville, V; André, F; Navas, C; Grönroos, E; Nicol, D; Hazell, S; Hrouda, D; O'Brien, T; Matthews, N; Phillimore, B; Begum, S; Rabinowitz, A; Biggs, J; Bates, PA; McDonald, NQ; Stamp, G; Spencer-Dene, B; Hsieh, JJ; Xu, J; Pickering, L; Gore, M; Larkin, J; Swanton, C (2014-08-27)
      Background Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution.Results We perform whole exome sequencing on four clear ...
    • Efficacy and toxicity of rechallenge with combination immune checkpoint blockade in metastatic melanoma: a case series. 

      Spain, L; Walls, G; Messiou, C; Turajlic, S; Gore, M; Larkin, J (2017-01)
      Background The efficacy and potential toxicity of rechallenge with combination ipilimumab and nivolumab has not been described. Retreatment of patients with immune checkpoint inhibitors in the setting of prior significant ...
    • Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies. 

      Arce Vargas, F; Furness, AJS; Litchfield, K; Joshi, K; Rosenthal, R; Ghorani, E; Solomon, I; Lesko, MH; Ruef, N; Roddie, C; Henry, JY; Spain, L; Ben Aissa, A; Georgiou, A; Wong, YNS; Smith, M; Strauss, D; Hayes, A; Nicol, D; O'Brien, T; Mårtensson, L; Ljungars, A; Teige, I; Frendéus, B; TRACERx Melanoma; TRACERx Renal; TRACERx Lung consortia; Pule, M; Marafioti, T; Gore, M; Larkin, J; Turajlic, S; Swanton, C; Peggs, KS; Quezada, SA (2018-04)
      With the use of a mouse model expressing human Fc-gamma receptors (FcγRs), we demonstrated that antibodies with isotypes equivalent to ipilimumab and tremelimumab mediate intra-tumoral regulatory T (Treg) cell depletion ...
    • Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors. 

      Arce Vargas, F; Furness, AJS; Solomon, I; Joshi, K; Mekkaoui, L; Lesko, MH; Miranda Rota, E; Dahan, R; Georgiou, A; Sledzinska, A; Ben Aissa, A; Franz, D; Werner Sunderland, M; Wong, YNS; Henry, JY; O'Brien, T; Nicol, D; Challacombe, B; Beers, SA; Melanoma TRACERx Consortium; Renal TRACERx Consortium; Lung TRACERx Consortium; Turajlic, S; Gore, M; Larkin, J; Swanton, C; Chester, KA; Pule, M; Ravetch, JV; Marafioti, T; Peggs, KS; Quezada, SA (2017-04-11)
      CD25 is expressed at high levels on regulatory T (Treg) cells and was initially proposed as a target for cancer immunotherapy. However, anti-CD25 antibodies have displayed limited activity against established tumors. We ...
    • Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. 

      Turajlic, S; Litchfield, K; Xu, H; Rosenthal, R; McGranahan, N; Reading, JL; Wong, YNS; Rowan, A; Kanu, N; Al Bakir, M; Chambers, T; Salgado, R; Savas, P; Loi, S; Birkbak, NJ; Sansregret, L; Gore, M; Larkin, J; Quezada, SA; Swanton, C (2017-08)
      Background The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the ...
    • Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. 

      Spain, L; Walls, G; Julve, M; O'Meara, K; Schmid, T; Kalaitzaki, E; Turajlic, S; Gore, M; Rees, J; Larkin, J (2017-02)
      Background Treatment with immune checkpoint inhibitors (ICPi) has greatly improved survival for patients with advanced melanoma in recent years. Anti-CTLA-4 and anti-PD1 antibodies have been approved following large Phase ...
    • Preclinical Evidence That Trametinib Enhances the Response to Antiangiogenic Tyrosine Kinase Inhibitors in Renal Cell Carcinoma. 

      Bridgeman, VL; Wan, E; Foo, S; Nathan, MR; Welti, JC; Frentzas, S; Vermeulen, PB; Preece, N; Springer, CJ; Powles, T; Nathan, PD; Larkin, J; Gore, M; Vasudev, NS; Reynolds, AR (2016-01)
      Sunitinib and pazopanib are antiangiogenic tyrosine kinase inhibitors (TKI) used to treat metastatic renal cell carcinoma (RCC). However, the ability of these drugs to extend progression-free and overall survival in this ...
    • Prognostic markers and tumour growth kinetics in melanoma patients progressing on vemurafenib. 

      Seifert, H; Fisher, R; Martin-Liberal, J; Edmonds, K; Hughes, P; Khabra, K; Gore, M; Larkin, J (2016-04)
      The BRAF inhibitor vemurafenib is an effective drug in patients with BRAF mutant metastatic melanoma, but resistance occurs after a median of 6 months. The anti-CTLA4-antibody, ipilimumab, is a standard first-line and ...
    • Systematic evaluation of the prognostic impact and intratumour heterogeneity of clear cell renal cell carcinoma biomarkers. 

      Gulati, S; Martinez, P; Joshi, T; Birkbak, NJ; Santos, CR; Rowan, AJ; Pickering, L; Gore, M; Larkin, J; Szallasi, Z; Bates, PA; Swanton, C; Gerlinger, M (2014-11)
      Background Candidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated.Objective To validate published ccRCC prognostic biomarkers in an independent ...
    • Thyroid abnormalities following the use of cytotoxic T-lymphocyte antigen-4 and programmed death receptor protein-1 inhibitors in the treatment of melanoma. 

      Morganstein, DL; Lai, Z; Spain, L; Diem, S; Levine, D; Mace, C; Gore, M; Larkin, J (2017-04)
      Context Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy.Objective To determine the burden of thyroid dysfunction in ...
    • Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. 

      Turajlic, S; Xu, H; Litchfield, K; Rowan, A; Chambers, T; Lopez, JI; Nicol, D; O'Brien, T; Larkin, J; Horswell, S; Stares, M; Au, L; Jamal-Hanjani, M; Challacombe, B; Chandra, A; Hazell, S; Eichler-Jonsson, C; Soultati, A; Chowdhury, S; Rudman, S; Lynch, J; Fernando, A; Stamp, G; Nye, E; Jabbar, F; Spain, L; Lall, S; Guarch, R; Falzon, M; Proctor, I; Pickering, L; Gore, M; Watkins, TBK; Ward, S; Stewart, A; DiNatale, R; Becerra, MF; Reznik, E; Hsieh, JJ; Richmond, TA; Mayhew, GF; Hill, SM; McNally, CD; Jones, C; Rosenbaum, H; Stanislaw, S; Burgess, DL; Alexander, NR; Swanton, C; PEACE; TRACERx Renal Consortium (2018-04-12)
      Clear-cell renal cell carcinoma (ccRCC) exhibits a broad range of metastatic phenotypes that have not been systematically studied to date. Here, we analyzed 575 primary and 335 metastatic biopsies across 100 patients with ...
    • Vessel co-option is common in human lung metastases and mediates resistance to anti-angiogenic therapy in preclinical lung metastasis models. 

      Bridgeman, VL; Vermeulen, PB; Foo, S; Bilecz, A; Daley, F; Kostaras, E; Nathan, MR; Wan, E; Frentzas, S; Schweiger, T; Hegedus, B; Hoetzenecker, K; Renyi-Vamos, F; Kuczynski, EA; Vasudev, NS; Larkin, J; Gore, M; Dvorak, HF; Paku, S; Kerbel, RS; Dome, B; Reynolds, AR (2017-02)
      Anti-angiogenic therapies have shown limited efficacy in the clinical management of metastatic disease, including lung metastases. Moreover, the mechanisms via which tumours resist anti-angiogenic therapies are poorly ...