Pub Date : 2024-07-05DOI: 10.1038/s41568-024-00724-4
Gabrielle Brewer
Lim et al. show that ASS1, silenced in many cancer types, is a metabolic checkpoint that, following DNA damage, halts cell cycle progression by restricting nucleotide synthesis and p53-related gene transcription.
Lim 等人的研究表明，ASS1 在许多癌症类型中都处于沉默状态，它是一种代谢检查点，在 DNA 损伤后，通过限制核苷酸合成和 p53 相关基因的转录来阻止细胞周期的进展。
{"title":"ASS1: Guardian of the genome","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00724-4","DOIUrl":"10.1038/s41568-024-00724-4","url":null,"abstract":"Lim et al. show that ASS1, silenced in many cancer types, is a metabolic checkpoint that, following DNA damage, halts cell cycle progression by restricting nucleotide synthesis and p53-related gene transcription.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 8","pages":"521-521"},"PeriodicalIF":72.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-04DOI: 10.1038/s41568-024-00722-6
Daniela Senft
In this study, Allan Balmain and colleagues used a mouse model to monitor stem cell networks at single-cell resolution during skin carcinogenesis, revealing two cancer stem cell states, rapid cycling and plasticity, between which cells can transition to drive tumour initiation, progression and therapy resistance.
{"title":"Carcinogenesis at single-cell resolution","authors":"Daniela Senft","doi":"10.1038/s41568-024-00722-6","DOIUrl":"10.1038/s41568-024-00722-6","url":null,"abstract":"In this study, Allan Balmain and colleagues used a mouse model to monitor stem cell networks at single-cell resolution during skin carcinogenesis, revealing two cancer stem cell states, rapid cycling and plasticity, between which cells can transition to drive tumour initiation, progression and therapy resistance.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 8","pages":"520-520"},"PeriodicalIF":72.5,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-02DOI: 10.1038/s41568-024-00718-2
Samantha Hindle, Richard Sever
Preprints benefit researchers’ careers in a number of ways. They allow authors to control the timing of dissemination of their work and provide early evidence of productivity that can be cited in job applications, grant proposals and reviews for tenure and other awards. The practice of posting preprint manuscripts on servers such as bioRxiv has become increasingly common. In this Comment, Hindle and Sever explore the utility of preprints for advancing researchers careers.
预印本在很多方面有利于研究人员的职业生涯。预印本允许作者控制其研究成果的传播时间，并提供早期的生产力证据，这些证据可以在工作申请、拨款建议以及终身职位和其他奖励的评审中引用。在 bioRxiv 等服务器上发布预印本手稿的做法越来越普遍。在这篇评论中，Hindle 和 Sever 探讨了预印本对促进研究人员职业发展的作用。
{"title":"Preprints as tools to advance careers","authors":"Samantha Hindle, Richard Sever","doi":"10.1038/s41568-024-00718-2","DOIUrl":"10.1038/s41568-024-00718-2","url":null,"abstract":"Preprints benefit researchers’ careers in a number of ways. They allow authors to control the timing of dissemination of their work and provide early evidence of productivity that can be cited in job applications, grant proposals and reviews for tenure and other awards. The practice of posting preprint manuscripts on servers such as bioRxiv has become increasingly common. In this Comment, Hindle and Sever explore the utility of preprints for advancing researchers careers.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 9","pages":"591-592"},"PeriodicalIF":72.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01DOI: 10.1038/s41568-024-00719-1
Amy E. Turriff, Diana W. Bianchi
The ability of prenatal cell-free DNA sequencing to incidentally detect occult maternal malignancies was first documented over a decade ago, yet coordinated follow-up of pregnant people who receive these results is still lacking in many countries. Here we provide a call to action for oncologists to become more involved in diagnosing and managing these cases.
产前无细胞 DNA 测序能够偶然检测出隐匿的母体恶性肿瘤，这在十多年前就已被首次记录在案，但在许多国家，对收到这些结果的孕妇仍然缺乏协调的随访。在此，我们呼吁肿瘤学家更多地参与这些病例的诊断和管理。
{"title":"Oncologists must act to manage cancer detected through prenatal screening","authors":"Amy E. Turriff, Diana W. Bianchi","doi":"10.1038/s41568-024-00719-1","DOIUrl":"10.1038/s41568-024-00719-1","url":null,"abstract":"The ability of prenatal cell-free DNA sequencing to incidentally detect occult maternal malignancies was first documented over a decade ago, yet coordinated follow-up of pregnant people who receive these results is still lacking in many countries. Here we provide a call to action for oncologists to become more involved in diagnosing and managing these cases.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 10","pages":"649-650"},"PeriodicalIF":72.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477010","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-25DOI: 10.1038/s41568-024-00717-3
Gabrielle Brewer
Patient progression and response to immunotherapy are directly influenced by the presence and quality of tumour-infiltrating leukocytes (TILs). In a recent Cell publication, Wang, Zeng et al. demonstrate the functional role of circadian rhythms in altering TIL functionality and quantity, highlighting the therapeutic potential of leveraging this understanding.
肿瘤浸润白细胞（TILs）的存在和质量直接影响着患者的病情进展和对免疫疗法的反应。在最近发表的《细胞》（Cell）杂志上，Wang、Zeng 等人证明了昼夜节律在改变 TIL 功能和数量方面的功能性作用，并强调了利用这一认识的治疗潜力；
{"title":"The rhythm of the night","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00717-3","DOIUrl":"10.1038/s41568-024-00717-3","url":null,"abstract":"Patient progression and response to immunotherapy are directly influenced by the presence and quality of tumour-infiltrating leukocytes (TILs). In a recent Cell publication, Wang, Zeng et al. demonstrate the functional role of circadian rhythms in altering TIL functionality and quantity, highlighting the therapeutic potential of leveraging this understanding. ","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 8","pages":"521-521"},"PeriodicalIF":72.5,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141448177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-21DOI: 10.1038/s41568-024-00720-8
In our Roadmap articles, we ask authors to provide a sense of direction to a field, to encourage new lines of thinking and experimentation, as well as opportunities for collaboration. This month, Nature Reviews Cancer launches Roadmap articles, in which we ask authors to provide a sense of direction to a field to encourage new lines of thinking and experimentation, as well as opportunities for collaboration.
{"title":"The road less travelled","authors":"","doi":"10.1038/s41568-024-00720-8","DOIUrl":"10.1038/s41568-024-00720-8","url":null,"abstract":"In our Roadmap articles, we ask authors to provide a sense of direction to a field, to encourage new lines of thinking and experimentation, as well as opportunities for collaboration. This month, Nature Reviews Cancer launches Roadmap articles, in which we ask authors to provide a sense of direction to a field to encourage new lines of thinking and experimentation, as well as opportunities for collaboration.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 8","pages":"515-515"},"PeriodicalIF":72.5,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41568-024-00720-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141435862","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-19DOI: 10.1038/s41568-024-00708-4
Adrienne Boire, Katy Burke, Thomas R. Cox, Theresa Guise, Mariam Jamal-Hanjani, Tobias Janowitz, Rosandra Kaplan, Rebecca Lee, Charles Swanton, Matthew G. Vander Heiden, Erik Sahai
Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier deployment of existing strategies to prolong quality of life is highly desirable. In this Roadmap, we review the proximal causes of mortality in patients with cancer and discuss current knowledge about the interconnections between mechanisms that contribute to mortality, before finally proposing new and improved avenues for data collection, research and the development of treatment strategies that may improve quality of life for patients. In this Roadmap, Boire et al. consider the immediate causes of mortality in patients with cancer, a topic not often considered in either preclinical or clinical research, and provide recommendations for how we can stimulate research to advance our mechanistic understanding of these causes with a long-term view to improving the quality of life for patients with late-stage cancer.
{"title":"Why do patients with cancer die?","authors":"Adrienne Boire, Katy Burke, Thomas R. Cox, Theresa Guise, Mariam Jamal-Hanjani, Tobias Janowitz, Rosandra Kaplan, Rebecca Lee, Charles Swanton, Matthew G. Vander Heiden, Erik Sahai","doi":"10.1038/s41568-024-00708-4","DOIUrl":"10.1038/s41568-024-00708-4","url":null,"abstract":"Cancer is a major cause of global mortality, both in affluent countries and increasingly in developing nations. Many patients with cancer experience reduced life expectancy and have metastatic disease at the time of death. However, the more precise causes of mortality and patient deterioration before death remain poorly understood. This scarcity of information, particularly the lack of mechanistic insights, presents a challenge for the development of novel treatment strategies to improve the quality of, and potentially extend, life for patients with late-stage cancer. In addition, earlier deployment of existing strategies to prolong quality of life is highly desirable. In this Roadmap, we review the proximal causes of mortality in patients with cancer and discuss current knowledge about the interconnections between mechanisms that contribute to mortality, before finally proposing new and improved avenues for data collection, research and the development of treatment strategies that may improve quality of life for patients. In this Roadmap, Boire et al. consider the immediate causes of mortality in patients with cancer, a topic not often considered in either preclinical or clinical research, and provide recommendations for how we can stimulate research to advance our mechanistic understanding of these causes with a long-term view to improving the quality of life for patients with late-stage cancer.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 8","pages":"578-589"},"PeriodicalIF":72.5,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1038/s41568-024-00704-8
J. C. Ashworth, T. R. Cox
The need for improved prediction of clinical response is driving the development of cancer models with enhanced physiological relevance. A new concept of ‘precision biomaterials’ is emerging, encompassing patient-mimetic biomaterial models that seek to accurately detect, treat and model cancer by faithfully recapitulating key microenvironmental characteristics. Despite recent advances allowing tissue-mimetic stiffness and molecular composition to be replicated in vitro, approaches for reproducing the 3D fibre architectures found in tumour extracellular matrix (ECM) remain relatively unexplored. Although the precise influences of patient-specific fibre architecture are unclear, we summarize the known roles of tumour fibre architecture, underlining their implications in cell–matrix interactions and ultimately clinical outcome. We then explore the challenges in reproducing tissue-specific 3D fibre architecture(s) in vitro, highlighting relevant biomaterial fabrication techniques and their benefits and limitations. Finally, we discuss imaging and image analysis techniques (focussing on collagen I-optimized approaches) that could hold the key to mapping tumour-specific ECM into high-fidelity biomaterial models. We anticipate that an interdisciplinary approach, combining materials science, cancer research and image analysis, will elucidate the role of 3D fibre architecture in tumour development, leading to the next generation of patient-mimetic models for mechanistic studies and drug discovery. Although there has been increasing interest in developing models that mimic the tumour microenvironment (TME), these models often fail to replicate the complex 3D fibre architectures observed in tumours. Here, Ashworth and Cox address this, discuss the current design and fabrication challenges, and outline state-of-the-art biomaterial technologies useful for recreating tissue-specific 3D architectures in vitro.
提高临床反应预测能力的需求正在推动具有更强生理相关性的癌症模型的发展。精准生物材料 "这一新概念正在兴起，它包括模拟患者的生物材料模型，旨在通过忠实再现关键的微环境特征来准确检测、治疗和模拟癌症。尽管最近取得了一些进展，可以在体外复制组织仿真硬度和分子组成，但复制肿瘤细胞外基质（ECM）中的三维纤维结构的方法仍相对欠缺。虽然患者特异性纤维结构的确切影响尚不清楚，但我们总结了肿瘤纤维结构的已知作用，强调了它们在细胞-基质相互作用以及最终临床结果中的意义。然后，我们探讨了在体外再现组织特异性三维纤维结构所面临的挑战，重点介绍了相关的生物材料制造技术及其优势和局限性。最后，我们讨论了成像和图像分析技术（重点是胶原蛋白 I 优化方法），这些技术可能是将肿瘤特异性 ECM 映射到高保真生物材料模型中的关键。我们预计，结合材料科学、癌症研究和图像分析的跨学科方法将阐明三维纤维结构在肿瘤发生发展中的作用，从而为机理研究和药物发现提供下一代病人仿真模型。
{"title":"The importance of 3D fibre architecture in cancer and implications for biomaterial model design","authors":"J. C. Ashworth, T. R. Cox","doi":"10.1038/s41568-024-00704-8","DOIUrl":"10.1038/s41568-024-00704-8","url":null,"abstract":"The need for improved prediction of clinical response is driving the development of cancer models with enhanced physiological relevance. A new concept of ‘precision biomaterials’ is emerging, encompassing patient-mimetic biomaterial models that seek to accurately detect, treat and model cancer by faithfully recapitulating key microenvironmental characteristics. Despite recent advances allowing tissue-mimetic stiffness and molecular composition to be replicated in vitro, approaches for reproducing the 3D fibre architectures found in tumour extracellular matrix (ECM) remain relatively unexplored. Although the precise influences of patient-specific fibre architecture are unclear, we summarize the known roles of tumour fibre architecture, underlining their implications in cell–matrix interactions and ultimately clinical outcome. We then explore the challenges in reproducing tissue-specific 3D fibre architecture(s) in vitro, highlighting relevant biomaterial fabrication techniques and their benefits and limitations. Finally, we discuss imaging and image analysis techniques (focussing on collagen I-optimized approaches) that could hold the key to mapping tumour-specific ECM into high-fidelity biomaterial models. We anticipate that an interdisciplinary approach, combining materials science, cancer research and image analysis, will elucidate the role of 3D fibre architecture in tumour development, leading to the next generation of patient-mimetic models for mechanistic studies and drug discovery. Although there has been increasing interest in developing models that mimic the tumour microenvironment (TME), these models often fail to replicate the complex 3D fibre architectures observed in tumours. Here, Ashworth and Cox address this, discuss the current design and fabrication challenges, and outline state-of-the-art biomaterial technologies useful for recreating tissue-specific 3D architectures in vitro.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 7","pages":"461-479"},"PeriodicalIF":72.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141333528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-17DOI: 10.1038/s41568-024-00699-2
Rachael M. Zemek, Valsamo Anagnostou, Inês Pires da Silva, Georgina V. Long, Willem Joost Lesterhuis
Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. To improve outcomes, a multitude of clinical trials are testing combinations of ICT with various other treatment modalities. Ideally, those combination treatments should take time-dependent immunological events into account. Recent studies have started to map the dynamic cellular and molecular changes that occur during treatment with ICT, in the tumour and systemically. Here, we overlay the dynamic ICT response with the therapeutic response following surgery, radiotherapy, chemotherapy and targeted therapies. We propose that by combining treatments in a time-conscious manner, we may optimally exploit the interactions between the individual therapies. The tumour immune microenvironment greatly affects responses to immune checkpoint therapies. In this Perspective, Zemek et al. explore the dynamic changes in response to both immunotherapy and conventional treatment and advocate for strategic combination therapies over time to enhance antitumour immune responses.
{"title":"Exploiting temporal aspects of cancer immunotherapy","authors":"Rachael M. Zemek, Valsamo Anagnostou, Inês Pires da Silva, Georgina V. Long, Willem Joost Lesterhuis","doi":"10.1038/s41568-024-00699-2","DOIUrl":"10.1038/s41568-024-00699-2","url":null,"abstract":"Many mechanisms underlying an effective immunotherapy-induced antitumour response are transient and critically time dependent. This is equally true for several immunological events in the tumour microenvironment induced by other cancer treatments. Immune checkpoint therapy (ICT) has proven to be very effective in the treatment of some cancers, but unfortunately, with many cancer types, most patients do not experience a benefit. To improve outcomes, a multitude of clinical trials are testing combinations of ICT with various other treatment modalities. Ideally, those combination treatments should take time-dependent immunological events into account. Recent studies have started to map the dynamic cellular and molecular changes that occur during treatment with ICT, in the tumour and systemically. Here, we overlay the dynamic ICT response with the therapeutic response following surgery, radiotherapy, chemotherapy and targeted therapies. We propose that by combining treatments in a time-conscious manner, we may optimally exploit the interactions between the individual therapies. The tumour immune microenvironment greatly affects responses to immune checkpoint therapies. In this Perspective, Zemek et al. explore the dynamic changes in response to both immunotherapy and conventional treatment and advocate for strategic combination therapies over time to enhance antitumour immune responses.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 7","pages":"480-497"},"PeriodicalIF":72.5,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141334407","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-13DOI: 10.1038/s41568-024-00700-y
Jan Remsik, Adrienne Boire
The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation and malignancy. Spread of systemic cancer into this space, termed leptomeningeal metastasis, occurs in 5–10% of patients with solid tumours and portends a bleak clinical prognosis. Previous, predominantly descriptive, clinical studies have provided few insights. Recent development of preclinical leptomeningeal metastasis models, alongside genomic, transcriptomic and proteomic sequencing efforts, has provided groundwork for mechanistic understanding and identification of long-needed therapeutic targets. Although previously understood as an anatomically isolated compartment, the leptomeninges are increasingly appreciated as a major conduit of communication between the systemic circulation and the central nervous system. Despite the unique nature of the leptomeningeal microenvironment, the general principles of metastasis hold true: cells metastasizing to the leptomeninges must gain access to the new environment, survive within the space and evade the immune system. The study of leptomeningeal metastasis has the potential to uncover novel site-specific metastatic principles and illuminate the physiology of the leptomeningeal space. In this Review, we provide a biology-focused overview of how metastatic cells reach the leptomeninges, thrive in this nutritionally sparse environment and evade the detection of the omnipresent immune system. Metastasis to the leptomeninges causes substantial neurological morbidity and mortality. Owing to the lack of mechanistic studies in this area, patients still face a bleak clinical prognosis. In this Review, Remsik and Boire provide a biology-focused overview of recent developments enabled by preclinical models and omics analyses and outline the need for further mechanistic research on leptomeningeal metastasis.
{"title":"The path to leptomeningeal metastasis","authors":"Jan Remsik, Adrienne Boire","doi":"10.1038/s41568-024-00700-y","DOIUrl":"10.1038/s41568-024-00700-y","url":null,"abstract":"The leptomeninges, the cerebrospinal-fluid-filled tissues surrounding the central nervous system, play host to various pathologies including infection, neuroinflammation and malignancy. Spread of systemic cancer into this space, termed leptomeningeal metastasis, occurs in 5–10% of patients with solid tumours and portends a bleak clinical prognosis. Previous, predominantly descriptive, clinical studies have provided few insights. Recent development of preclinical leptomeningeal metastasis models, alongside genomic, transcriptomic and proteomic sequencing efforts, has provided groundwork for mechanistic understanding and identification of long-needed therapeutic targets. Although previously understood as an anatomically isolated compartment, the leptomeninges are increasingly appreciated as a major conduit of communication between the systemic circulation and the central nervous system. Despite the unique nature of the leptomeningeal microenvironment, the general principles of metastasis hold true: cells metastasizing to the leptomeninges must gain access to the new environment, survive within the space and evade the immune system. The study of leptomeningeal metastasis has the potential to uncover novel site-specific metastatic principles and illuminate the physiology of the leptomeningeal space. In this Review, we provide a biology-focused overview of how metastatic cells reach the leptomeninges, thrive in this nutritionally sparse environment and evade the detection of the omnipresent immune system. Metastasis to the leptomeninges causes substantial neurological morbidity and mortality. Owing to the lack of mechanistic studies in this area, patients still face a bleak clinical prognosis. In this Review, Remsik and Boire provide a biology-focused overview of recent developments enabled by preclinical models and omics analyses and outline the need for further mechanistic research on leptomeningeal metastasis.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 7","pages":"448-460"},"PeriodicalIF":72.5,"publicationDate":"2024-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141315648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：