Shepherd, S.T., Litchfield, K. & Turajlic, S.
(2019). Searching for the needle in the haystack: deconvoluting the evolutionary dynamics of residual disease in human glioblastoma. Annals of oncology,
Vol.30
(3),
pp. 355-357.
Turajlic, S.
(2019). Standing on the shoulders of giants. Nature medicine,
Vol.25
(3),
pp. 357-357.
Spain, L., Tippu, Z., Larkin, J.M., Carr, A. & Turajlic, S.
(2019). How we treat neurological toxicity from immune checkpoint inhibitors. Esmo open,
Vol.4
(Suppl 4),
pp. e000540-e000540.
show abstract
Neurological adverse events from immune checkpoint inhibition are increasingly recognised, especially with combination anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) and anti-programmed death receptor 1 (anti-PD-1) therapies. Their presenting symptoms and signs are often subacute and highly variable, reflecting the numerous components of the nervous system. Given the risk of substantial morbidity and mortality, it is important to inform patients of symptoms that may be of concern, and to assess any suspected toxicity promptly. As with other immune-related adverse events, the cornerstone of management is administration of corticosteroids. Specialist neurology input is vital in this group of patients to guide appropriate investigations and tailor treatment strategies..
Amaria, R.N., Menzies, A.M., Burton, E.M., Scolyer, R.A., Tetzlaff, M.T., Antdbacka, R., Ariyan, C., Bassett, R., Carter, B., Daud, A., et al.
(2019). Neoadjuvant systemic therapy in melanoma: recommendations of the International Neoadjuvant Melanoma Consortium. The lancet oncology,
Vol.20
(7),
pp. e378-e389.
Turajlic, S., Sottoriva, A., Graham, T. & Swanton, C.
(2019). Resolving genetic heterogeneity in cancer. Nature reviews genetics,
Vol.20
(7),
pp. 404-416.
Flynn, M., Pickering, L., Larkin, J. & Turajlic, S.
(2018). Immune-checkpoint inhibitors in melanoma and kidney cancer: from sequencing to rational selection. Therapeutic advances in medical oncology,
Vol.10,
pp. 175883591877742-175883591877742.
Turajlic, S., Swanton, C. & Boshoff, C.
(2018). Kidney cancer: The next decade. The journal of experimental medicine,
Vol.215
(10),
pp. 2477-2479.
show abstract
Chris Boshoff, Senior Vice President of Immuno-Oncology, Translational and Early Development at Pfizer, and colleagues Samra Turajlic and Charles Swanton from the Francis Crick Institute and University College London give us their personal point of view on new insights and future therapeutic approaches for renal cancer..
Lim, K.H., Spain, L., Barker, C., Georgiou, A., Walls, G., Gore, M., Turajlic, S., Board, R., Larkin, J.M. & Lorigan, P., et al.
(2018). Contemporary outcomes from the use of regular imaging to detect relapse in high-risk cutaneous melanoma. Esmo open,
Vol.3
(2),
pp. e000317-e000317.
Abbosh, C., Birkbak, N.J., Wilson, G.A., Jamal-Hanjani, M., Constantin, T., Salari, R., Le Quesne, J., Moore, D.A., Veeriah, S., Rosenthal, R., et al.
(2018). Erratum: Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature,
Vol.554
(7691),
pp. 264-264.
Arce Vargas, F., Furness, A.J., Litchfield, K., Joshi, K., Rosenthal, R., Ghorani, E., Solomon, I., Lesko, M.H., Ruef, N., Roddie, C., et al.
(2018). Fc Effector Function Contributes to the Activity of Human Anti-CTLA-4 Antibodies. Cancer cell,
Vol.33
(4),
pp. 649-663.e4.
Turajlic, S., Xu, H., Litchfield, K., Rowan, A., Horswell, S., Chambers, T., O’Brien, T., Lopez, J.I., Watkins, T.B., Nicol, D., et al.
(2018). Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal. Cell,
Vol.173
(3),
pp. 595-610.e11.
Turajlic, S., Xu, H., Litchfield, K., Rowan, A., Chambers, T., Lopez, J.I., Nicol, D., O’Brien, T., Larkin, J., Horswell, S., et al.
(2018). Tracking Cancer Evolution Reveals Constrained Routes to Metastases: TRACERx Renal. Cell,
Vol.173
(3),
pp. 581-594.e12.
Mitchell, T.J., Turajlic, S., Rowan, A., Nicol, D., Farmery, J.H., O’Brien, T., Martincorena, I., Tarpey, P., Angelopoulos, N., Yates, L.R., et al.
(2018). Timing the Landmark Events in the Evolution of Clear Cell Renal Cell Cancer: TRACERx Renal. Cell,
Vol.173
(3),
pp. 611-623.e17.
Tio, M., Rai, R., Ezeoke, O.M., McQuade, J.L., Zimmer, L., Khoo, C., Park, J.J., Spain, L., Turajlic, S., Ardolino, L., et al.
(2018). Anti-PD-1/PD-L1 immunotherapy in patients with solid organ transplant, HIV or hepatitis B/C infection. European journal of cancer,
Vol.104,
pp. 137-144.
Turajlic, S. & Larkin, J.
(2018). Immunotherapy for Melanoma Metastatic to the Brain. New england journal of medicine,
Vol.379
(8),
pp. 789-790.
Spain, L., Walls, G., Messiou, C., Turajlic, S., Gore, M. & Larkin, J.
(2017). Efficacy and toxicity of rechallenge with combination immune checkpoint blockade in metastatic melanoma: a case series. Cancer immunology, immunotherapy,
Vol.66
(1),
pp. 113-117.
Arce Vargas, F., Furness, A.J., Solomon, I., Joshi, K., Mekkaoui, L., Lesko, M.H., Miranda Rota, E., Dahan, R., Georgiou, A., Sledzinska, A., et al.
(2017). Fc-Optimized Anti-CD25 Depletes Tumor-Infiltrating Regulatory T Cells and Synergizes with PD-1 Blockade to Eradicate Established Tumors. Immunity,
Vol.46
(4),
pp. 577-586.
Abbosh, C., Birkbak, N.J., Wilson, G.A., Jamal-Hanjani, M., Constantin, T., Salari, R., Le Quesne, J., Moore, D.A., Veeriah, S., Rosenthal, R., et al.
(2017). Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution. Nature,
Vol.545
(7655),
pp. 446-451.
Jamal-Hanjani, M., Wilson, G.A., McGranahan, N., Birkbak, N.J., Watkins, T.B., Veeriah, S., Shafi, S., Johnson, D.H., Mitter, R., Rosenthal, R., et al.
(2017). Tracking the Evolution of Non–Small-Cell Lung Cancer. New england journal of medicine,
Vol.376
(22),
pp. 2109-2121.
Turajlic, S. & Swanton, C.
(2017). Implications of cancer evolution for drug development. Nature reviews drug discovery,
Vol.16
(7),
pp. 441-442.
Turajlic, S., Litchfield, K., Xu, H., Rosenthal, R., McGranahan, N., Reading, J.L., Wong, Y.N., Rowan, A., Kanu, N., Al Bakir, M., et al.
(2017). Insertion-and-deletion-derived tumour-specific neoantigens and the immunogenic phenotype: a pan-cancer analysis. The lancet oncology,
Vol.18
(8),
pp. 1009-1021.
Litchfield, K., Turajlic, S. & Swanton, C.
(2017). The GENIE Is Out of the Bottle: Landmark Cancer Genomics Dataset Released. Cancer discovery,
Vol.7
(8),
pp. 796-798.
(2017). TRACERx Renal: tracking renal cancer evolution through therapy. Nature reviews urology,
Vol.14
(10),
pp. 575-576.
McGranahan, N., Rosenthal, R., Hiley, C.T., Rowan, A.J., Watkins, T.B., Wilson, G.A., Birkbak, N.J., Veeriah, S., Van Loo, P., Herrero, J., et al.
(2017). Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. Cell,
Vol.171
(6),
pp. 1259-1271.e11.
Spain, L., Higgins, R., Gopalakrishnan, K., Turajlic, S., Gore, M. & Larkin, J.
(2016). Acute renal allograft rejection after immune checkpoint inhibitor therapy for metastatic melanoma. Annals of oncology,
Vol.27
(6),
pp. 1135-1137.
Turajlic, S. & Swanton, C.
(2016). Metastasis as an evolutionary process. Science,
Vol.352
(6282),
pp. 169-175.
Turajlic, S. & Larkin, J.
(2016). Systemic treatment of advanced papillary renal cell carcinoma: Where next?. European journal of cancer,
Vol.69,
pp. 223-225.
Joshi, K., Furness, A.J., Oakes, T., Heather, J., Spain, L.A., Wong, Y.N., Ben Aissa, A., Stares, M., Smith, M.J., Strauss, D.C., et al.
(2016). Defining the mechanisms of response and resistance to anti-PD-1 therapy: An exploratory phase II study of pembrolizumab in advanced melanoma (ADAPTeM). Journal of clinical oncology,
Vol.34
(15_suppl),
pp. TPS9599-TPS9599.
Spain, L., Walls, G., Julve, M., O'Meara, K., Schmid, T., Kalaitzaki, E., Turajlic, S., Gore, M., Rees, J. & Larkin, J., et al.
(2016). Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Ann oncol,
.
Turajlic, S., McGranahan, N. & Swanton, C.
(2015). Inferring mutational timing and reconstructing tumour evolutionary histories. Biochimica et biophysica acta (bba) - reviews on cancer,
Vol.1855
(2),
pp. 264-275.
Gulati, S., Turajlic, S., Larkin, J., Bates, P.A. & Swanton, C.
(2015). Relapse models for clear cell renal carcinoma. The lancet oncology,
Vol.16
(8),
pp. e376-e378.
Soultati, A., Stares, M., Swanton, C., Larkin, J. & Turajlic, S.
(2015). How should clinicians address intratumour heterogeneity in clear cell renal cell carcinoma?. Current opinion in urology,
Vol.25
(5),
pp. 358-366.
Turajlic, S., Larkin, J. & Swanton, C.
(2015). Academically led clinical trials: challenges and opportunities: Figure 1. Annals of oncology,
Vol.26
(10),
pp. 2010-2011.
Turajlic, S. & Swanton, C.
(2015). Tracking tumour evolution through liquid biopsy. Nature reviews clinical oncology,
Vol.12
(10),
pp. 565-566.
Turajlic, S., Larkin, J. & Swanton, C.
(2015). SnapShot: Renal Cell Carcinoma. Cell,
Vol.163
(6),
pp. 1556-1556.e1.
Turajlic, S., Furney, S.J., Stamp, G., Rana, S., Ricken, G., Oduko, Y., Saturno, G., Springer, C., Hayes, A., Gore, M., et al.
(2014). Whole-genome sequencing reveals complex mechanisms of intrinsic resistance to BRAF inhibition. Annals of oncology,
Vol.25
(5),
pp. 959-967.
Furney, S.J., Turajlic, S., Stamp, G., Thomas, J.M., Hayes, A., Strauss, D., Gavrielides, M., Xing, W., Gore, M., Larkin, J., et al.
(2014). The mutational burden of acral melanoma revealed by whole-genome sequencing and comparative analysis. Pigment cell & melanoma research,
Vol.27
(5),
pp. 835-838.
Sanchez-Laorden, B., Viros, A., Girotti, M.R., Pedersen, M., Saturno, G., Zambon, A., Niculescu-Duvaz, D., Turajlic, S., Hayes, A., Gore, M., et al.
(2014). BRAF Inhibitors Induce Metastasis in RAS Mutant or Inhibitor-Resistant Melanoma Cells by Reactivating MEK and ERK Signaling. Science signaling,
Vol.7
(318),
pp. ra30-ra30.
Furney, S.J., Pedersen, M., Gentien, D., Dumont, A.G., Rapinat, A., Desjardins, L., Turajlic, S., Piperno-Neumann, S., de la Grange, P., Roman-Roman, S., et al.
(2013). SF3B1 Mutations Are Associated with Alternative Splicing in Uveal Melanoma. Cancer discovery,
Vol.3
(10),
pp. 1122-1129.
Girotti, M.R., Pedersen, M., Sanchez-Laorden, B., Viros, A., Turajlic, S., Niculescu-Duvaz, D., Zambon, A., Sinclair, J., Hayes, A., Gore, M., et al.
(2013). Inhibiting EGF Receptor or SRC Family Kinase Signaling Overcomes BRAF Inhibitor Resistance in Melanoma. Cancer discovery,
Vol.3
(2),
pp. 158-167.
Khattak, M., Fisher, R., Turajlic, S. & Larkin, J.
(2013). Targeted therapy and immunotherapy in advanced melanoma: an evolving paradigm. Therapeutic advances in medical oncology,
Vol.5
(2),
pp. 105-118.
Furney, S.J., Turajlic, S., Stamp, G., Nohadani, M., Carlisle, A., Thomas, J.M., Hayes, A., Strauss, D., Gore, M., van den Oord, J., et al.
(2013). Genome sequencing of mucosal melanomas reveals that they are driven by distinct mechanisms from cutaneous melanoma. The journal of pathology,
Vol.230
(3),
pp. 261-269.
Turajlic, S., Ali, Z., Yousaf, N. & Larkin, J.
(2013). Phase I/II RAF kinase inhibitors in cancer therapy. Expert opinion on investigational drugs,
Vol.22
(6),
pp. 739-749.
Turajlic, S., Furney, S.J., Lambros, M.B., Mitsopoulos, C., Kozarewa, I., Geyer, F.C., MacKay, A., Hakas, J., Zvelebil, M., Lord, C.J., et al.
(2012). Whole genome sequencing of matched primary and metastatic acral melanomas. Genome research,
Vol.22
(2),
pp. 196-207.
Natrajan, R., Mackay, A., Lambros, M.B., Weigelt, B., Wilkerson, P.M., Manie, E., Grigoriadis, A., A'Hern, R., van der Groep, P., Kozarewa, I., et al.
(2012). A whole-genome massively parallel sequencing analysis of BRCA1 mutant oestrogen receptor-negative and -positive breast cancers. The journal of pathology,
Vol.227
(1),
pp. 29-41.
Furney, S.J., Turajlic, S., Fenwick, K., Lambros, M.B., MacKay, A., Ricken, G., Mitsopoulos, C., Kozarewa, I., Hakas, J., Zvelebil, M., et al.
(2012). Genomic characterisation of acral melanoma cell lines. Pigment cell & melanoma research,
Vol.25
(4),
pp. 488-492.
Larkin, J.M., Turajlic, S., Nathan, P.D., Lorigan, P., Stamp, G., Gonzalez de Castro, D., Martin, N., Griffiths, J., Edmonds, K., Sarker, S., et al.
(2011). A phase II trial of nilotinib in the treatment of patients with KIT mutated advanced acral and mucosal melanoma (NICAM). J clin oncol,
Vol.29
(15_suppl),
p. TPS229.
show abstract
TPS229 Background: Recent studies have indicated that KIT mutations occur in approximately 20% of acral and mucosal melanomas (Curtin, al. 2006; Beadling, et al. 2008). Several case reports have shown that KIT mutated melanomas can respond to treatment with KIT inhibitors (Hodi et al. 2008; Lutzky et al. 2008; Quintas-Cardama et al. 2008; Handolias et al. 2010; Itoh, et al. 2010; Satzger et al. 2010; Terheyden et al. 2010; Woodman and Davies 2010) suggesting that such tumours critically depend on upregulated KIT signalling. Nilotinib, which potently inhibits the tyrosine kinase activity of BCR-ABL and KIT, has been evaluated in patients with advanced KIT mutated GIST and has shown clinical efficacy at well tolerated doses (Demetri et al. 2009; Montemurro et al. 2009; Schlemmer et al. 2010). METHODS: NICAM is a single arm 2-stage open label phase II study of nilotinib in KIT mutated advanced mucosal or acral melanoma. Patients with KIT mutations known to confer resistance to nilotinib are excluded. The primary objective in this feasibility study is to evaluate the efficacy of nilotinib in KIT mutated advanced mucosal and acral melanoma with a primary endpoint of progression free survival at 6 months. Secondary endpoints include response rate at 12 weeks; overall survival; toxicity of treatment; correlation between the response to nilotinib and KIT genotype, KIT gene copy number and KIT expression. In addition, the following will be explored: 1. Suppression of phosphorylation of KIT and downstream pathways on day 15 tumour biopsies; 2. Possible mechanisms of resistance by analysis of biopsies obtained at disease progression; 3. The use of circulating tumour DNA for non-invasive KIT mutational testing; 4. Genetic lesions that potentially cooperate with oncogenic KIT in melanoma (using Next Generation Sequencing). All patients are treated until disease progression or unacceptable toxicity. If 2 or more of the first 9 patients are progression free at 6 months, patient entry will continue into the second stage until a total of 24 patients have been recruited. To date, 45 patients have been registered and screened for KIT mutation and 5 patients have entered the study..
Perez, A., Turajlic, S., Szyszko, T., O'Doherty, M., Calonje, E., Harries, M. & Acland, K.
(2010). Generalized melanosis and melanuria in a patient with metastatic melanoma. Clinical and experimental dermatology,
Vol.35
(3),
pp. e37-e39.
Spain, L., Walls, G., Julve, M., O’Meara, K., Schmid, T., Kalaitzaki, E., Turajlic, S., Gore, M., Rees, J. & Larkin, J., et al.
Neurotoxicity from immune-checkpoint inhibition in the treatment of melanoma: a single centre experience and review of the literature. Annals of oncology,
,
pp. mdw558-mdw558.
O’Reilly, A., Hughes, P., Mann, J., Lai, Z., Teh, J.J., Mclean, E., Edmonds, K., Lingard, K., Chauhan, D., Lynch, J., et al.
An immunotherapy survivor population: health-related quality of life and toxicity in patients with metastatic melanoma treated with immune checkpoint inhibitors. Supportive care in cancer,
.
Ferronika, P., Hof, J., Kats-Ugurlu, G., Sijmons, R.H., Terpstra, M.M., de Lange, K., Leliveld-Kors, A., Westers, H. & Kok, K.
Comprehensive Profiling of Primary and Metastatic ccRCC Reveals a High Homology of the Metastases to a Subregion of the Primary Tumour. Cancers,
Vol.11
(6),
pp. 812-812.
show abstract
While intratumour genetic heterogeneity of primary clear cell renal cell carcinoma (ccRCC) is well characterized, the genomic profiles of metastatic ccRCCs are seldom studied. We profiled the genomes and transcriptomes of a primary tumour and matched metastases to better understand the evolutionary processes that lead to metastasis. In one ccRCC patient, four regions of the primary tumour, one region of the thrombus in the inferior vena cava, and four lung metastases (including one taken after pegylated (PEG)-interferon therapy) were analysed separately. Each sample was analysed for copy number alterations and somatic mutations by whole exome sequencing. We also evaluated gene expression profiles for this patient and 15 primary tumour and 15 metastasis samples from four additional patients. Copy number profiles of the index patient showed two distinct subgroups: one consisted of three primary tumours with relatively minor copy number changes, the other of a primary tumour, the thrombus, and the lung metastases, all with a similar copy number pattern and tetraploid-like characteristics. Somatic mutation profiles indicated parallel clonal evolution with similar numbers of private mutations in each primary tumour and metastatic sample. Expression profiling of the five patients revealed significantly changed expression levels of 57 genes between primary tumours and metastases, with enrichment in the extracellular matrix cluster. The copy number profiles suggest a punctuated evolution from a subregion of the primary tumour. This process, which differentiated the metastases from the primary tumours, most likely occurred rapidly, possibly even before metastasis formation. The evolutionary patterns we deduced from the genomic alterations were also reflected in the gene expression profiles..