British Journal of Cancer

Mitchell, T; Neal, D E

doi: 10.1038/bjc.2015.234pmid: 26125442

Prostate cancers are highly prevalent in the developed world, with inheritable risk contributing appreciably to tumour development. Genomic heterogeneity within individual prostate glands and between patients derives predominantly from structural variants and copy-number aberrations. Subtypes of prostate cancers are being delineated through the increasing use of next-generation sequencing, but these subtypes are yet to be used to guide the prognosis or therapeutic strategy. Herein, we review our current knowledge of the mutational landscape of human prostate cancer, describing what is known of the common mutations underpinning its development. We evaluate recurrent prostate-specific mutations prior to discussing the mutational events that are shared both in prostate cancer and across multiple cancer types. From these data, we construct a putative overview of the genomic evolution of human prostate cancer.

Jänne, P A; Smith, I; McWalter, G; Mann, H; Dougherty, B; Walker, J; Orr, M C M; Hodgson, D R; Shaw, A T; Pereira, J R; Jeannin, G; Vansteenkiste, J; Barrios, C H; Franke, F A; Crinò, L; Smith, P

doi: 10.1038/bjc.2015.215pmid: 26125448

Pine, J K; Morris, E; Hutchins, G G; West, N P; Jayne, D G; Quirke, P; Prasad, K R

doi: 10.1038/bjc.2015.87pmid: 26125452

Parnaby, C N; Scott, N W; Ramsay, G; MacKay, C; Samuel, L; Murray, G I; Loudon, M A

doi: 10.1038/bjc.2015.211pmid: 26079302

Wu, C; Mikhail, S; Wei, L; Timmers, C; Tahiri, S; Neal, A; Walker, J; El-Dika, S; Blazer, M; Rock, J; Clark, D J; Yang, X; Chen, J L; Liu, J; Knopp, M V; Bekaii-Saab, T

doi: 10.1038/bjc.2015.197pmid: 26151457

Beije, N; Kraan, J; Taal, W; van der Holt, B; Oosterkamp, H M; Walenkamp, A M; Beerepoot, L; Hanse, M; van Linde, M E; Otten, A; Vernhout, R M; de Vos, F Y F; Gratama, J W; Sleijfer, S; van den Bent, M J

doi: 10.1038/bjc.2015.191pmid:

Wong, E T; Lok, E; Gautam, S; Swanson, K D

doi: 10.1038/bjc.2015.238pmid: 26125449

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Background:</jats:title> <jats:p>Patients with recurrent glioblastoma have a poor outcome. Data from the phase III registration trial comparing tumour-treating alternating electric fields (TTFields) <jats:italic>vs</jats:italic> chemotherapy provided a unique opportunity to study dexamethasone effects on patient outcome unencumbered by the confounding immune and myeloablative side effects of chemotherapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods:</jats:title> <jats:p>Using an unsupervised binary partitioning algorithm, we segregated both cohorts of the trial based on the dexamethasone dose that yielded the greatest statistical difference in overall survival (OS). The results were validated in a separate cohort treated in a single institution with TTFields and their T lymphocytes were correlated with OS.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats:p>Patients who used dexamethasone doses &gt;4.1 mg per day had a significant reduction in OS when compared with those who used ⩽4.1 mg per day, 4.8 <jats:italic>vs</jats:italic> 11.0 months respectively (<jats:italic>χ</jats:italic> <jats:sup>2</jats:sup>=34.6, <jats:italic>P</jats:italic>&lt;0.0001) in the TTField-treated cohort and 6.0 <jats:italic>vs</jats:italic> 8.9 months respectively (<jats:italic>χ</jats:italic> <jats:sup>2</jats:sup>=10.0, <jats:italic>P</jats:italic>&lt;0.0015) in the chemotherapy-treated cohort. In a single institution validation cohort treated with TTFields, the median OS of patients who used dexamethasone &gt;4.1 mg per day was 3.2 months compared with those who used ⩽4.1 mg per day was 8.7 months (<jats:italic>χ</jats:italic> <jats:sup>2</jats:sup>=11.1, <jats:italic>P</jats:italic>=0.0009). There was a significant correlation between OS and T-lymphocyte counts.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>Dexamethasone exerted profound effects on both TTFields and chemotherapy efficacy resulting in lower patient OS. Therefore, global immunosuppression by dexamethasone likely interferes with immune functions that are necessary for the treatment of glioblastoma.</jats:p> </jats:sec>

Xu, S; Adisetiyo, H; Tamura, S; Grande, F; Garofalo, A; Roy-Burman, P; Neamati, N

doi: 10.1038/bjc.2015.228pmid: 26103574

Higashi, T; Hayashi, H; Ishimoto, T; Takeyama, H; Kaida, T; Arima, K; Taki, K; Sakamoto, K; Kuroki, H; Okabe, H; Nitta, H; Hashimoto, D; Chikamoto, A; Beppu, T; Baba, H

doi: 10.1038/bjc.2015.170pmid: 26125451

Tittarelli, A; Guerrero, I; Tempio, F; Gleisner, M A; Avalos, I; Sabanegh, S; Ortíz, C; Michea, L; López, M N; Mendoza-Naranjo, A; Salazar-Onfray, F

doi: 10.1038/bjc.2015.162pmid: 26135897