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Y chromosome loss in cancer drives growth by evasion of adaptive immunity
Loss of the Y chromosome in tumour cells is associated with a poor prognosis for patients with bladder cancer by causing local T cell exhaustion, which also increases the response to immune checkpoint blockade therapy.
- Hany A. Abdel-Hafiz
- , Johanna M. Schafer
- & Dan Theodorescu
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Article
| Open Access
African-specific molecular taxonomy of prostate cancer
A molecular taxonomy for prostate cancer reveals a subtype associated with copy-number loss found in African and European populations that predicts poor outcomes and two subtypes—one associated with high mutational noise and one with copy-number gain—specific to African populations.
- Weerachai Jaratlerdsiri
- , Jue Jiang
- & Vanessa M. Hayes
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Article |
Deep whole-genome ctDNA chronology of treatment-resistant prostate cancer
Deep whole-genome sequencing of serial blood samples and matched metastatic tissue reveals that circulating tumour DNA profiling enables detailed study of treatment-driven subclone dynamics, epigenomics and genome-wide somatic evolution in metastatic human cancers.
- Cameron Herberts
- , Matti Annala
- & Alexander W. Wyatt
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Article
| Open Access
The renal lineage factor PAX8 controls oncogenic signalling in kidney cancer
The lineage transcription factor PAX8 is shown to play a pivotal part in determining cancer risk in clear cell renal cell carcinoma, providing insights into how genetic mutations lead to specific types of cancer.
- Saroor A. Patel
- , Shoko Hirosue
- & Sakari Vanharanta
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Article
| Open Access
Targeting SWI/SNF ATPases in enhancer-addicted prostate cancer
PROTAC degrader–induced SWI/SNF inactivation abolishes DNA accessibility at enhancer elements of oncogenes and also tempers supra-physiologic expression of driver transcription factors, resulting in potent inhibition of tumour growth in mouse models.
- Lanbo Xiao
- , Abhijit Parolia
- & Arul M. Chinnaiyan
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Article |
ctDNA guiding adjuvant immunotherapy in urothelial carcinoma
The authors report on prospective exploratory analyses of circulating tumour DNA in an urothelial carcinoma immunotherapy clinical trial.
- Thomas Powles
- , Zoe June Assaf
- & Sanjeev Mariathasan
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Article |
A genomic and epigenomic atlas of prostate cancer in Asian populations
Genomic, transcriptomic and DNA methylation data from tissue samples from 208 Chinese patients with prostate cancer define the landscape of alterations in this population, and comparison with data from Western cohorts suggests that the disease may stratify into different molecular subtypes.
- Jing Li
- , Chuanliang Xu
- & Yinghao Sun
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Letter |
FOXA1 mutations alter pioneering activity, differentiation and prostate cancer phenotypes
Mutations in the transcription factor FOXA1 that are common in prostate cancer result in gain-of-function effects that promote changes in the differentiation of tumour cells.
- Elizabeth J. Adams
- , Wouter R. Karthaus
- & Charles L. Sawyers
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Article |
Progenitors from the central nervous system drive neurogenesis in cancer
In a mouse model of prostate cancer, neural progenitors from the central nervous system that express doublecortin infiltrate tumours and metastases, and can generate new adrenergic neurons in tumours.
- Philippe Mauffrey
- , Nicolas Tchitchek
- & Claire Magnon
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Article |
IL-23 secreted by myeloid cells drives castration-resistant prostate cancer
IL-23 produced by myeloid-derived suppressor cells regulates castration resistance in prostate cancer by sustaining androgen receptor signalling.
- Arianna Calcinotto
- , Clarissa Spataro
- & Andrea Alimonti
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Letter |
TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells
In humans, TGFβ signalling is associated with lack of response to immunotherapy in immune-excluded tumours; in mouse models of this immune phenotype, robust tumour infiltration by T cells and tumour regression are observed only when checkpoint inhibition is combined with inhibition of TGFβ signalling.
- Sanjeev Mariathasan
- , Shannon J. Turley
- & Thomas Powles
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Outlook |
Unlocking bladder cancer
The diagnostics, treatment and five-year survival rates for bladder cancer are largely unchanged since the 1990s. Research into cancer genomics, risk factors and immune therapies could hold the key to progress against this malignant disease.
- Chris Berdik
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Outlook |
Bladder cancer: 4 big questions
Tackling the challenges of genomics and studies of the immune system should help to create much-needed diagnostics and treatments.
- Chris Berdik
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Outlook |
Genetics: A clearer view
Researchers delving into the details of bladder cancer are finding a rich trove of genetic information.
- Jeanne Erdmann
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Outlook |
Egypt: The flatworm's revenge
How Egyptian men swapped one type of bladder cancer for another.
- Louise Sarant
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Outlook |
Microbiome: A bag of surprises
Once thought to be sterile, the bladder contains microbes that could influence the development and treatment of cancer.
- Claire Ainsworth
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Outlook |
Theatre: The bladder's tale
What happens when a professor of theatre finds out she has bladder cancer? She writes a one-woman play about it, of course.
- Tammy Worth
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Outlook |
Perspective: Bridging the gender gap
Bladder cancer is more deadly in women than in men. That needs to change, say James McKiernan and Denise Asafu-Adjei.
- James McKiernan
- & Denise Asafu-Adjei
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Outlook |
Q&A: Mechele Leon: Take it away
Mechele Leon, an associate professor of theatre at the University of Kansas in Lawrence, was diagnosed with bladder cancer in March 2016. After treatment, Leon was left with no bladder, a urostomy bag, and a story to tell — which became a one-woman play called Bladder Interrupted.
- Tammy Worth
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Outlook |
Therapeutics: Spoilt for choice
People with metastatic bladder cancer once faced meagre treatment options and a grim prognosis. But immunotherapy has started to yield results.
- Michael Eisenstein
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Outlook |
Diagnostics: A flow of information
Many non-invasive approaches to detecting bladder cancer are showing promise — including smart toilets.
- Chelsea Wald
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Letter |
ERF mutations reveal a balance of ETS factors controlling prostate oncogenesis
In prostate cancer, the oncogenicity of transcription factor ERG is mediated, in part, by competition with another member of the ETS family, ERF.
- Rohit Bose
- , Wouter R. Karthaus
- & Charles L. Sawyers
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Letter |
Effective combinatorial immunotherapy for castration-resistant prostate cancer
A new chimaeric mouse model of metastatic castration-resistant prostate cancer to efficiently test combination therapies in an autochthonous setting.
- Xin Lu
- , James W. Horner
- & Ronald A. DePinho
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Letter |
Synthetic essentiality of chromatin remodelling factor CHD1 in PTEN-deficient cancer
The gene CHD1 is synthetic essential in PTEN-deficient prostate and breast cancers.
- Di Zhao
- , Xin Lu
- & Ronald A. DePinho
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Article |
Genomic hallmarks of localized, non-indolent prostate cancer
Genomic analyses of localized, non-indolent prostate cancer identify recurrent aberrations that can predict relapse, and also highlight differences between early prostate cancer and metastatic, castration-resistant disease.
- Michael Fraser
- , Veronica Y. Sabelnykova
- & Paul C. Boutros
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Letter |
Fumarate is an epigenetic modifier that elicits epithelial-to-mesenchymal transition
Accumulation of fumarate resulting from mutations in fumarate hydratase,which are associated with renal and other cancers, is shown to induce epithelial-to-mesenchymal transition—a process associated with cancer initiation.
- Marco Sciacovelli
- , Emanuel Gonçalves
- & Christian Frezza
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Letter |
Redirecting abiraterone metabolism to fine-tune prostate cancer anti-androgen therapy
The prostate cancer drug abiraterone can be metabolized into several substances with different effects, and optimization of this process could be helpful for fine-tuning the treatment of prostate cancer.
- Zhenfei Li
- , Mohammad Alyamani
- & Nima Sharifi
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Letter |
Conversion of abiraterone to D4A drives anti-tumour activity in prostate cancer
The drug abiraterone is converted to Δ4-abiraterone (D4A) in mice and patients with prostate cancer, which has more potent anti-tumour activity and may lead to more effective therapies.
- Zhenfei Li
- , Andrew C. Bishop
- & Nima Sharifi
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Outlook |
Statistics: Attacking an epidemic
Despite a huge amount of funding and research, regional and individual differences in cancer trends make it a hard disease to wipe out. By Mike May.
- Mike May
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Article
| Open Access
Comprehensive molecular characterization of clear cell renal cell carcinoma
The Cancer Genome Atlas Research Network reports an integrative analysis of more than 400 samples of clear cell renal cell carcinoma based on genomic, DNA methylation, RNA and proteomic characterisation; frequent mutations were identified in the PI(3)K/AKT pathway, suggesting this pathway might be a potential therapeutic target, among the findings is also a demonstration of metabolic remodelling which correlates with tumour stage and severity.
- Chad J. Creighton
- , Margaret Morgan
- & Heidi J. Sofia.
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Letter |
COUP-TFII inhibits TGF-β-induced growth barrier to promote prostate tumorigenesis
A cell-autonomous role for the COUP-TFII transcription factor in prostate cancer cells is identified, in which COUP-TFII inhibits TGF-β signalling by binding to SMAD4; COUP-TFII promotes prostate tumorigenesis and metastasis in a mouse model, and is associated with more aggressive disease in human prostate cancers.
- Jun Qin
- , San-Pin Wu
- & Sophia Y. Tsai
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Letter |
The mutational landscape of lethal castration-resistant prostate cancer
Exome sequencing is used to investigate the role of mutations and copy number aberrations in metastatic castration-resistant prostate cancer, revealing recurrent mutations in multiple chromatin/histone modifying genes, as well as genes involved in androgen signalling.
- Catherine S. Grasso
- , Yi-Mi Wu
- & Scott A. Tomlins
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Research Highlights |
Blocking tumour sugar metabolism
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Letter |
Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001
The structures of CYP17A1 with steroid inhibitors abiraterone or TOK-001 provide a better understanding of the enzyme’s catalytic capabilities and inhibition, and hence assist in understanding steroidogenic diseases and designing drugs to improve the treatment of prostate and other steroid-responsive cancers.
- Natasha M. DeVore
- & Emily E. Scott
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Editorial |
The PSA position
The US government must take a firm stance on whether prostate-cancer screening is justified.
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Letter |
A SUMOylation-defective MITF germline mutation predisposes to melanoma and renal carcinoma
- Corine Bertolotto
- , Fabienne Lesueur
- & Brigitte Bressac-de Paillerets
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Letter |
Haem oxygenase is synthetically lethal with the tumour suppressor fumarate hydratase
- Christian Frezza
- , Liang Zheng
- & Eyal Gottlieb
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News |
Urine predicts prostate cancer risk
Test could reduce unnecessary needle biopsies.
- Virginia Gewin
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Letter |
COP1 is a tumour suppressor that causes degradation of ETS transcription factors
- Alberto C. Vitari
- , Kevin G. Leong
- & Vishva M. Dixit
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Letter |
Reprogramming transcription by distinct classes of enhancers functionally defined by eRNA
- Dong Wang
- , Ivan Garcia-Bassets
- & Xiang-Dong Fu
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Letter |
Hedgehog/Wnt feedback supports regenerative proliferation of epithelial stem cells in bladder
The maintenance and regeneration of the epithelium of the adult bladder is poorly understood yet it is a clinically relevant process during urinary tract infections and bladder cancer. This study provides insight into the cellular and molecular mechanisms underlying the regenerative response to injury within the mammalian urinary bladder. Upon injury by bacterial infection or chemical agents, a Shh and Wnt signalling feedback circuit between basal cells of the urothelium and the stromal cells that underlie them leads to regenerative proliferation of the bladder epithelia.
- Kunyoo Shin
- , John Lee
- & Philip A. Beachy
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Article
| Open Access
The genomic complexity of primary human prostate cancer
Prostate cancer is a common cause of male cancer-related deaths. Complete sequencing of prostate cancer genomes now reveals previously unknown balanced rearrangements. Single-nucleotide resolution afforded by sequencing indicates that complex rearrangements may arise from transcriptional or chromatin aberrancies and engage prostate tumorigenic mechanisms.
- Michael F. Berger
- , Michael S. Lawrence
- & Levi A. Garraway
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Letter |
LRRC26 auxiliary protein allows BK channel activation at resting voltage without calcium
Here the authors show that in non-excitable LNCaP prostate cancer cells, the large-conductance, voltage- and calcium-activated potassium (BK) channel can be activated at negative voltages without rises in intracellular Ca2+ concentration, by interacting with an auxiliary protein, the leucine-rich repeat containing protein 26. This auxiliary protein modulates BK channel gating by enhancing the allosteric coupling between voltage-sensor activation and the channel's closed–open transition.
- Jiusheng Yan
- & Richard W. Aldrich
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Research Highlights |
Cancer genomics: Probing prostate cancer
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Research Highlights |
Cancer detection: Tracking roving cancer cells
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Letter |
B-cell-derived lymphotoxin promotes castration-resistant prostate cancer
In a mouse model of prostate cancer it is shown that infiltrating B cells promote tumorigenesis by secreting lymphotoxin. Lymphotoxin accelerates the emergence of castration-resistant prostate tumours in this model. Interfering with this pathway may offer therapeutic strategies for androgen-independent prostate cancer.
- Massimo Ammirante
- , Jun-Li Luo
- & Michael Karin
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Research Highlights |
Cancer biology: Arsenic activation
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News |
Blame it on the B cells
Immune cells seem to spark recurrent prostate cancer in mice.
- Brian Vastag
Targeting myeloid chemotaxis to reverse prostate cancer therapy resistance
Bladder cancer