Pub Date : 2024-05-13DOI: 10.1038/s41585-024-00894-8
David J. Benjamin, Omid Yazdanpanah, Arash Rezazadeh Kalebasty
As the population of gender minorities grows in the setting of rising incidence of cancers globally, health-care professionals and institutions must be prepared to provide inclusive care. Individual-level training as well as institutional-level efforts on gender identity data collection and creation of inclusive clinical spaces could help mitigate health-care disparities.
{"title":"Overcoming barriers in cancer care for gender minorities","authors":"David J. Benjamin, Omid Yazdanpanah, Arash Rezazadeh Kalebasty","doi":"10.1038/s41585-024-00894-8","DOIUrl":"10.1038/s41585-024-00894-8","url":null,"abstract":"As the population of gender minorities grows in the setting of rising incidence of cancers globally, health-care professionals and institutions must be prepared to provide inclusive care. Individual-level training as well as institutional-level efforts on gender identity data collection and creation of inclusive clinical spaces could help mitigate health-care disparities.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 6","pages":"325-326"},"PeriodicalIF":15.3,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140915001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.1038/s41585-024-00874-y
Alessandro Larcher, Federico Belladelli, Francesco Cei, Chiara Re, Isaline Rowe, Francesco Montorsi, Umberto Capitanio, Andrea Salonia
Von Hippel–Lindau (VHL) disease is a rare genetic syndrome caused by a germline pathogenic variant in one VHL allele. Any somatic event disrupting the other allele induces VHL protein (pVHL) loss of function, ultimately leading to patients developing multiple tumours in multiple organs at multiple timepoints, and reducing life expectancy. Treatment of this complex, rare disease is often fragmented, as patients visit specialist clinicians in isolation at different medical centres. Consequently, patients can receive sub-optimal treatment that results in decreased quality of life and a poor experience of health care systems. In 2021, we established a comprehensive clinical centre at San Raffaele Hospital, Milan, devoted to VHL disease. The centre provides a structured programme for the diagnosis, surveillance and treatment of patients alongside research into VHL disease and involves a multidisciplinary team of dedicated physicians. This programme demonstrates the benefits of care centralization, including concentration of knowledge and services, synergy and multidisciplinary management, improved networking and patient resources, reducing health care costs, and fostering research and innovation. VHL disease provides an ideal model to assess the advantages of centralizing care for rare disease and represents an unparalleled opportunity to broaden our understanding of cancer biology in general. In this Perspective, Larcher et al. describe a dedicated treatment programme for Von Hippel–Lindau disease established at San Raffaele Hospital, which encompasses diagnosis, surveillance, treatment, research and outreach. The authors then discuss the benefits of care centralization for Von Hippel–Lindau disease and other rare diseases.
{"title":"Centralization of care for rare genetic syndromes associated with cancer: improving outcomes and advancing research on VHL disease","authors":"Alessandro Larcher, Federico Belladelli, Francesco Cei, Chiara Re, Isaline Rowe, Francesco Montorsi, Umberto Capitanio, Andrea Salonia","doi":"10.1038/s41585-024-00874-y","DOIUrl":"10.1038/s41585-024-00874-y","url":null,"abstract":"Von Hippel–Lindau (VHL) disease is a rare genetic syndrome caused by a germline pathogenic variant in one VHL allele. Any somatic event disrupting the other allele induces VHL protein (pVHL) loss of function, ultimately leading to patients developing multiple tumours in multiple organs at multiple timepoints, and reducing life expectancy. Treatment of this complex, rare disease is often fragmented, as patients visit specialist clinicians in isolation at different medical centres. Consequently, patients can receive sub-optimal treatment that results in decreased quality of life and a poor experience of health care systems. In 2021, we established a comprehensive clinical centre at San Raffaele Hospital, Milan, devoted to VHL disease. The centre provides a structured programme for the diagnosis, surveillance and treatment of patients alongside research into VHL disease and involves a multidisciplinary team of dedicated physicians. This programme demonstrates the benefits of care centralization, including concentration of knowledge and services, synergy and multidisciplinary management, improved networking and patient resources, reducing health care costs, and fostering research and innovation. VHL disease provides an ideal model to assess the advantages of centralizing care for rare disease and represents an unparalleled opportunity to broaden our understanding of cancer biology in general. In this Perspective, Larcher et al. describe a dedicated treatment programme for Von Hippel–Lindau disease established at San Raffaele Hospital, which encompasses diagnosis, surveillance, treatment, research and outreach. The authors then discuss the benefits of care centralization for Von Hippel–Lindau disease and other rare diseases.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 9","pages":"565-571"},"PeriodicalIF":12.1,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140881286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-08DOI: 10.1038/s41585-024-00890-y
Lucy Greenwald, Daniel R. Dickstein, Barbara Chubak, Deborah C. Marshall
Definitions of sexual arousal dysfunction in the International Classification of Diseases use sex-specific binaries that omit the erectile basis of arousal in females. To provide equitable health care for all people with erectile dysfunction, these definitions must be de-gendered.
{"title":"We all get erections — de-gendering sexual arousal dysfunction in the ICD","authors":"Lucy Greenwald, Daniel R. Dickstein, Barbara Chubak, Deborah C. Marshall","doi":"10.1038/s41585-024-00890-y","DOIUrl":"10.1038/s41585-024-00890-y","url":null,"abstract":"Definitions of sexual arousal dysfunction in the International Classification of Diseases use sex-specific binaries that omit the erectile basis of arousal in females. To provide equitable health care for all people with erectile dysfunction, these definitions must be de-gendered.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 6","pages":"319-320"},"PeriodicalIF":15.3,"publicationDate":"2024-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140892226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1038/s41585-024-00891-x
Sarah Cosgriff, Stella Schneckenburger
Asexuality is often neglected in education and conversations around sexuality, making it essentially an ‘invisible orientation’. This lack of knowledge is associated with harmful misconceptions, which need challenging within the medical profession and in the general population to ensure inclusion of people who identify on the asexual spectrum.
{"title":"Asexuality: the invisible orientation","authors":"Sarah Cosgriff, Stella Schneckenburger","doi":"10.1038/s41585-024-00891-x","DOIUrl":"10.1038/s41585-024-00891-x","url":null,"abstract":"Asexuality is often neglected in education and conversations around sexuality, making it essentially an ‘invisible orientation’. This lack of knowledge is associated with harmful misconceptions, which need challenging within the medical profession and in the general population to ensure inclusion of people who identify on the asexual spectrum.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 6","pages":"321-322"},"PeriodicalIF":15.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1038/s41585-024-00877-9
Aaron Simoni, Laura Schwartz, Guillermo Yepes Junquera, Christina B. Ching, John David Spencer
Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.
泌尿道致病菌的抗生素耐药率不断上升，损害了患者的治疗效果，延长了住院时间。因此，需要采取新的策略来预防和控制尿路病原菌抗生素耐药性的扩散。在过去的二十年里，大量的临床工作和研究进展改变了尿路感染（UTI）的治疗和预防策略，以节约抗生素的使用。抗菌药物管理的出现、国家协会制定的政策以及新型抗菌药物的开发塑造了现代UTI治疗方法。抗菌药物管理的发展、诊断技术的改进和普及，以及对微生物组如何影响 UTI 的进一步了解，都将推动未来 UTI 的治疗方法。未来的UTI治疗和预防策略可以采用新型杀菌化合物、新型和传统抗菌药的组合（以增强对细菌的杀伤力）、防止细菌附着于尿路上皮细胞的药物、再利用药物和疫苗，以遏制尿路致病菌抗生素耐药率的上升并改善UTI患者的治疗效果。
{"title":"Current and emerging strategies to curb antibiotic-resistant urinary tract infections","authors":"Aaron Simoni, Laura Schwartz, Guillermo Yepes Junquera, Christina B. Ching, John David Spencer","doi":"10.1038/s41585-024-00877-9","DOIUrl":"https://doi.org/10.1038/s41585-024-00877-9","url":null,"abstract":"<p>Rising rates of antibiotic resistance in uropathogenic bacteria compromise patient outcomes and prolong hospital stays. Consequently, new strategies are needed to prevent and control the spread of antibiotic resistance in uropathogenic bacteria. Over the past two decades, sizeable clinical efforts and research advances have changed urinary tract infection (UTI) treatment and prevention strategies to conserve antibiotic use. The emergence of antimicrobial stewardship, policies from national societies, and the development of new antimicrobials have shaped modern UTI practices. Future UTI management practices could be driven by the evolution of antimicrobial stewardship, improved and readily available diagnostics, and an improved understanding of how the microbiome affects UTI. Forthcoming UTI treatment and prevention strategies could employ novel bactericidal compounds, combinations of new and classic antimicrobials that enhance bacterial killing, medications that prevent bacterial attachment to uroepithelial cells, repurposing drugs, and vaccines to curtail the rising rates of antibiotic resistance in uropathogenic bacteria and improve outcomes in people with UTI.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"9 1","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-07DOI: 10.1038/s41585-024-00878-8
Masoud Bitaraf, Ranjith Ramasamy, Sanoj Punnen, Nima Sharifi
A subset of men with prostate cancer have elevated periprostatic androgens compared with levels in peripheral blood (termed the sneaky T phenomenon), which are associated with poor clinical outcomes after radical prostatectomy. These androgens are of testicular origin and reach the prostate, presumably through venous shunting. Varicocele physiology is accompanied by increased hydrostatic pressure within the pelvic venous system, providing a theoretical mechanistic explanation for the sneaky T phenomenon. These observations suggest a potential role for varicocele in contributing to prostate cancer pathophysiology through sneaky T, which if proved, could be a further indication for varicocele repair. Sneaky T can help to explain the differences in the natural history of benign or malignant prostatic diseases between individuals and could be a tool when deciding on the therapeutic course to take.
与外周血中的雄激素水平相比，一部分男性前列腺癌患者的前列腺周围雄激素水平升高（称为 "偷偷摸摸的T现象"），这与前列腺癌根治术后的不良临床结果有关。这些雄激素来源于睾丸，可能通过静脉分流到达前列腺。精索静脉曲张的生理学特征是盆腔静脉系统内的静水压升高，这为 "鬼鬼祟祟的T "现象提供了理论机制上的解释。这些观察结果表明，精索静脉曲张可能会通过 "鬼鬼祟祟的 T "现象导致前列腺癌的病理生理学。偷袭性 T 有助于解释良性或恶性前列腺疾病在自然病史上的个体差异，并可作为决定治疗方案的工具。
{"title":"Elevated periprostatic androgens, sneaky testosterone and its implications.","authors":"Masoud Bitaraf, Ranjith Ramasamy, Sanoj Punnen, Nima Sharifi","doi":"10.1038/s41585-024-00878-8","DOIUrl":"https://doi.org/10.1038/s41585-024-00878-8","url":null,"abstract":"<p><p>A subset of men with prostate cancer have elevated periprostatic androgens compared with levels in peripheral blood (termed the sneaky T phenomenon), which are associated with poor clinical outcomes after radical prostatectomy. These androgens are of testicular origin and reach the prostate, presumably through venous shunting. Varicocele physiology is accompanied by increased hydrostatic pressure within the pelvic venous system, providing a theoretical mechanistic explanation for the sneaky T phenomenon. These observations suggest a potential role for varicocele in contributing to prostate cancer pathophysiology through sneaky T, which if proved, could be a further indication for varicocele repair. Sneaky T can help to explain the differences in the natural history of benign or malignant prostatic diseases between individuals and could be a tool when deciding on the therapeutic course to take.</p>","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":" ","pages":""},"PeriodicalIF":15.3,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140876938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-03DOI: 10.1038/s41585-024-00872-0
Giandomenico Roviello, Matteo Santoni, Guru P. Sonpavde, Martina Catalano
Cisplatin-based chemotherapy is currently the first-line standard of care for patients with metastatic urothelial cancer (mUC); however, up to 50% of patients are ineligible for cisplatin, necessitating alternative treatment options. Immune checkpoint inhibitors have been shown to be effective in cisplatin-ineligible patients. However, despite advances in the first-line setting, the prognosis remains poor, and challenges persist in selecting optimal therapies, treatment sequences and combination regimens. Maintenance therapy with avelumab revealed improved overall (OS) and progression-free survival (PFS) compared with best supportive care alone in patients with platinum-responsive mUC. Antibody–drug conjugates and targeted therapy with fibroblast growth factor receptor (FGFR) inhibitors have shown promise in selected patients, particularly in patients with metastatic disease that has progressed despite platinum-based chemotherapy. At the European Society of Medical Oncology Congress in 2023, groundbreaking results were presented from two phase III trials, EV-302/KEYNOTE-A39 and CheckMate 901, focusing on previously untreated mUC. In the former, the combination of enfortumab vedotin and pembrolizumab showed significant improvements in OS, PFS and overall response rate compared with chemotherapy alone; the combination of nivolumab with gemcitabine–cisplatin chemotherapy demonstrated a significant extension in median OS, PFS and overall response rate compared with chemotherapy alone. In addition, erdafitinib therapy resulted in significantly longer OS than chemotherapy among patients with mUC and FGFR alterations after previous treatment with immune checkpoint inhibitors. This comprehensive summary of the current treatment landscape for mUC incorporates clinical trial evidence and discussion of agents that are currently under investigation to provide support for clinical decision making and understanding of future therapeutic approaches. Urothelial cancer is the tenth most diagnosed cancer worldwide, and between 5% and 10% of patients have metastatic disease at diagnosis. Furthermore, up to 50% of patients are ineligible for cisplatin, the first-line treatment option, and require alternative options. In this comprehensive Review, the authors discuss the current and future therapeutic options for advanced urothelial cancer, including chemotherapeutics, targeted therapies and antibody–drug conjugates, and consider how these agents might change patient management.
{"title":"The evolving treatment landscape of metastatic urothelial cancer","authors":"Giandomenico Roviello, Matteo Santoni, Guru P. Sonpavde, Martina Catalano","doi":"10.1038/s41585-024-00872-0","DOIUrl":"10.1038/s41585-024-00872-0","url":null,"abstract":"Cisplatin-based chemotherapy is currently the first-line standard of care for patients with metastatic urothelial cancer (mUC); however, up to 50% of patients are ineligible for cisplatin, necessitating alternative treatment options. Immune checkpoint inhibitors have been shown to be effective in cisplatin-ineligible patients. However, despite advances in the first-line setting, the prognosis remains poor, and challenges persist in selecting optimal therapies, treatment sequences and combination regimens. Maintenance therapy with avelumab revealed improved overall (OS) and progression-free survival (PFS) compared with best supportive care alone in patients with platinum-responsive mUC. Antibody–drug conjugates and targeted therapy with fibroblast growth factor receptor (FGFR) inhibitors have shown promise in selected patients, particularly in patients with metastatic disease that has progressed despite platinum-based chemotherapy. At the European Society of Medical Oncology Congress in 2023, groundbreaking results were presented from two phase III trials, EV-302/KEYNOTE-A39 and CheckMate 901, focusing on previously untreated mUC. In the former, the combination of enfortumab vedotin and pembrolizumab showed significant improvements in OS, PFS and overall response rate compared with chemotherapy alone; the combination of nivolumab with gemcitabine–cisplatin chemotherapy demonstrated a significant extension in median OS, PFS and overall response rate compared with chemotherapy alone. In addition, erdafitinib therapy resulted in significantly longer OS than chemotherapy among patients with mUC and FGFR alterations after previous treatment with immune checkpoint inhibitors. This comprehensive summary of the current treatment landscape for mUC incorporates clinical trial evidence and discussion of agents that are currently under investigation to provide support for clinical decision making and understanding of future therapeutic approaches. Urothelial cancer is the tenth most diagnosed cancer worldwide, and between 5% and 10% of patients have metastatic disease at diagnosis. Furthermore, up to 50% of patients are ineligible for cisplatin, the first-line treatment option, and require alternative options. In this comprehensive Review, the authors discuss the current and future therapeutic options for advanced urothelial cancer, including chemotherapeutics, targeted therapies and antibody–drug conjugates, and consider how these agents might change patient management.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 10","pages":"580-592"},"PeriodicalIF":12.1,"publicationDate":"2024-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-02DOI: 10.1038/s41585-024-00876-w
Chengheng Liao, Lianxin Hu, Qing Zhang
The distinct pathological and molecular features of kidney cancer in adaptation to oxygen homeostasis render this malignancy an attractive model for investigating hypoxia signalling and potentially developing potent targeted therapies. Hypoxia signalling has a pivotal role in kidney cancer, particularly within the most prevalent subtype, known as renal cell carcinoma (RCC). Hypoxia promotes various crucial pathological processes, such as hypoxia-inducible factor (HIF) activation, angiogenesis, proliferation, metabolic reprogramming and drug resistance, all of which contribute to kidney cancer development, growth or metastasis formation. A substantial portion of kidney cancers, in particular clear cell RCC (ccRCC), are characterized by a loss of function of Von Hippel–Lindau tumour suppressor (VHL), leading to the accumulation of HIF proteins, especially HIF2α, a crucial driver of ccRCC. Thus, therapeutic strategies targeting pVHL–HIF signalling have been explored in ccRCC, culminating in the successful development of HIF2α-specific antagonists such as belzutifan (PT2977), an FDA-approved drug to treat VHL-associated diseases including advanced-stage ccRCC. An increased understanding of hypoxia signalling in kidney cancer came from the discovery of novel VHL protein (pVHL) targets, and mechanisms of synthetic lethality with VHL mutations. These breakthroughs can pave the way for the development of innovative and potent combination therapies in kidney cancer. In this Review, the authors discuss hypoxia signalling and therapeutic strategies targeting this pathway in renal cell carcinoma, with a specific focus on clear cell renal cell carcinoma, in which hypoxia signalling is primarily driven by Von Hippel–Lindau tumour suppressor (VHL) loss.
{"title":"Von Hippel–Lindau protein signalling in clear cell renal cell carcinoma","authors":"Chengheng Liao, Lianxin Hu, Qing Zhang","doi":"10.1038/s41585-024-00876-w","DOIUrl":"10.1038/s41585-024-00876-w","url":null,"abstract":"The distinct pathological and molecular features of kidney cancer in adaptation to oxygen homeostasis render this malignancy an attractive model for investigating hypoxia signalling and potentially developing potent targeted therapies. Hypoxia signalling has a pivotal role in kidney cancer, particularly within the most prevalent subtype, known as renal cell carcinoma (RCC). Hypoxia promotes various crucial pathological processes, such as hypoxia-inducible factor (HIF) activation, angiogenesis, proliferation, metabolic reprogramming and drug resistance, all of which contribute to kidney cancer development, growth or metastasis formation. A substantial portion of kidney cancers, in particular clear cell RCC (ccRCC), are characterized by a loss of function of Von Hippel–Lindau tumour suppressor (VHL), leading to the accumulation of HIF proteins, especially HIF2α, a crucial driver of ccRCC. Thus, therapeutic strategies targeting pVHL–HIF signalling have been explored in ccRCC, culminating in the successful development of HIF2α-specific antagonists such as belzutifan (PT2977), an FDA-approved drug to treat VHL-associated diseases including advanced-stage ccRCC. An increased understanding of hypoxia signalling in kidney cancer came from the discovery of novel VHL protein (pVHL) targets, and mechanisms of synthetic lethality with VHL mutations. These breakthroughs can pave the way for the development of innovative and potent combination therapies in kidney cancer. In this Review, the authors discuss hypoxia signalling and therapeutic strategies targeting this pathway in renal cell carcinoma, with a specific focus on clear cell renal cell carcinoma, in which hypoxia signalling is primarily driven by Von Hippel–Lindau tumour suppressor (VHL) loss.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 11","pages":"662-675"},"PeriodicalIF":12.1,"publicationDate":"2024-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140821432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-05-01DOI: 10.1038/s41585-024-00889-5
Nicholas T. H. Farr, Victoria L. Workman, Christopher R. Chapple, Sheila MacNeil, Cornelia Rodenburg
Inflammatory and fibrotic responses to polypropylene mesh led to the withdrawal of this practice for treatment of stress urinary incontinence and pelvic organ prolapse in women in some countries. Improved material testing has been urged. We report poor responses of polypropylene mesh to repeated mechanical distension and macrophage interrogation. These results from preclinical in vitro testing show the potential of this approach for testing and improving materials before their introduction into the clinic.
{"title":"Strengthening preclinical testing to increase safety in surgical mesh","authors":"Nicholas T. H. Farr, Victoria L. Workman, Christopher R. Chapple, Sheila MacNeil, Cornelia Rodenburg","doi":"10.1038/s41585-024-00889-5","DOIUrl":"10.1038/s41585-024-00889-5","url":null,"abstract":"Inflammatory and fibrotic responses to polypropylene mesh led to the withdrawal of this practice for treatment of stress urinary incontinence and pelvic organ prolapse in women in some countries. Improved material testing has been urged. We report poor responses of polypropylene mesh to repeated mechanical distension and macrophage interrogation. These results from preclinical in vitro testing show the potential of this approach for testing and improving materials before their introduction into the clinic.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 9","pages":"515-516"},"PeriodicalIF":12.1,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817815","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-26DOI: 10.1038/s41585-024-00875-x
Xudong Ni, Yu Wei, Xiaomeng Li, Jian Pan, Bangwei Fang, Tingwei Zhang, Ying Lu, Dingwei Ye, Yao Zhu
Liver metastases from prostate cancer are associated with an aggressive disease course and poor prognosis. Results from autopsy studies indicate a liver metastasis prevalence of up to 25% in patients with advanced prostate cancer. Population data estimate that ~3–10% of patients with metastatic castration-resistant prostate cancer harbour liver metastases at the baseline, rising to 20–30% in post-treatment cohorts, suggesting that selective pressure imposed by novel therapies might promote metastatic spread to the liver. Liver metastases are associated with more aggressive tumour biology than lung metastases. Molecular profiling of liver lesions showed an enrichment of low androgen receptor, neuroendocrine phenotypes and high genomic instability. Despite advancements in molecular imaging modalities such as prostate-specific membrane antigen PET–CT, and liquid biopsy markers such as circulating tumour DNA, early detection of liver metastases from prostate cancer remains challenging, as both approaches are hampered by false positive and false negative results, impeding the accurate identification of early liver lesions. Current therapeutic strategies showed limited efficacy in this patient population. Emerging targeted radionuclide therapies, metastasis-directed therapy, and novel systemic agents have shown preliminary activity against liver metastases, but require further validation. Treatment with various novel prostate cancer therapies might lead to an increase in the prevalence of liver metastasis, underscoring the urgent need for coordinated efforts across preclinical and clinical researchers to improve characterization, monitoring, and management of liver metastases from prostate cancer. Elucidating molecular drivers of liver tropism and interactions with the liver microenvironment might ultimately help to identify actionable targets to enhance survival in this high-risk patient group. In this Review, the authors provide a comprehensive overview of the epidemiological characteristics, prognosis, biological mechanisms, detection methods and treatment options for liver metastasis in prostate cancer. Guidance for future research directions in the field is also provided.
{"title":"From biology to the clinic — exploring liver metastasis in prostate cancer","authors":"Xudong Ni, Yu Wei, Xiaomeng Li, Jian Pan, Bangwei Fang, Tingwei Zhang, Ying Lu, Dingwei Ye, Yao Zhu","doi":"10.1038/s41585-024-00875-x","DOIUrl":"10.1038/s41585-024-00875-x","url":null,"abstract":"Liver metastases from prostate cancer are associated with an aggressive disease course and poor prognosis. Results from autopsy studies indicate a liver metastasis prevalence of up to 25% in patients with advanced prostate cancer. Population data estimate that ~3–10% of patients with metastatic castration-resistant prostate cancer harbour liver metastases at the baseline, rising to 20–30% in post-treatment cohorts, suggesting that selective pressure imposed by novel therapies might promote metastatic spread to the liver. Liver metastases are associated with more aggressive tumour biology than lung metastases. Molecular profiling of liver lesions showed an enrichment of low androgen receptor, neuroendocrine phenotypes and high genomic instability. Despite advancements in molecular imaging modalities such as prostate-specific membrane antigen PET–CT, and liquid biopsy markers such as circulating tumour DNA, early detection of liver metastases from prostate cancer remains challenging, as both approaches are hampered by false positive and false negative results, impeding the accurate identification of early liver lesions. Current therapeutic strategies showed limited efficacy in this patient population. Emerging targeted radionuclide therapies, metastasis-directed therapy, and novel systemic agents have shown preliminary activity against liver metastases, but require further validation. Treatment with various novel prostate cancer therapies might lead to an increase in the prevalence of liver metastasis, underscoring the urgent need for coordinated efforts across preclinical and clinical researchers to improve characterization, monitoring, and management of liver metastases from prostate cancer. Elucidating molecular drivers of liver tropism and interactions with the liver microenvironment might ultimately help to identify actionable targets to enhance survival in this high-risk patient group. In this Review, the authors provide a comprehensive overview of the epidemiological characteristics, prognosis, biological mechanisms, detection methods and treatment options for liver metastasis in prostate cancer. Guidance for future research directions in the field is also provided.","PeriodicalId":19088,"journal":{"name":"Nature Reviews Urology","volume":"21 10","pages":"593-614"},"PeriodicalIF":12.1,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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