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)
      <h4>Background</h4>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 ...
    • 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)
      <h4>Background</h4>Genomic analysis of multi-focal renal cell carcinomas from an individual with a germline VHL mutation offers a unique opportunity to study tumor evolution.<h4>Results</h4>We perform whole exome sequencing ...
    • 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)
      <h4>Background</h4>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 ...
    • 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)
      <h4>Background</h4>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 ...
    • 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)
      <h4>Background</h4>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 ...
    • 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)
      <h4>Background</h4>Candidate biomarkers have been identified for clear cell renal cell carcinoma (ccRCC) patients, but most have not been validated.<h4>Objective</h4>To validate published ccRCC prognostic biomarkers in an ...
    • 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)
      <h4>Context</h4>Checkpoint inhibitors are emerging as important cancer therapies but are associated with a high rate of immune side effects, including endocrinopathy.<h4>Objective</h4>To determine the burden of thyroid ...
    • 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 ...