Pub Date : 2024-04-16DOI: 10.1038/s41568-024-00685-8
Stephen Gilbert, Jakob Nikolas Kather
Artificial narrow intelligence models, trained for specific intended purposes, have gained approval and recommendation for cancer treatment. Generalist medicial artificial intelligence (GMAI) models are now being developed for cancer treatment. Policy makers have a stark choice: radically adapt frameworks, block generalist approaches or force them onto narrower tracks. Generalist medical artificial intelligence (GMAI) models are gaining momentum in their applications for cancer treatment. In this Comment, Gilbert and Kather advocate for novel regulation of GMAI approaches to ensure patient safety and adequate physician support.
{"title":"Guardrails for the use of generalist AI in cancer care","authors":"Stephen Gilbert, Jakob Nikolas Kather","doi":"10.1038/s41568-024-00685-8","DOIUrl":"10.1038/s41568-024-00685-8","url":null,"abstract":"Artificial narrow intelligence models, trained for specific intended purposes, have gained approval and recommendation for cancer treatment. Generalist medicial artificial intelligence (GMAI) models are now being developed for cancer treatment. Policy makers have a stark choice: radically adapt frameworks, block generalist approaches or force them onto narrower tracks. Generalist medical artificial intelligence (GMAI) models are gaining momentum in their applications for cancer treatment. In this Comment, Gilbert and Kather advocate for novel regulation of GMAI approaches to ensure patient safety and adequate physician support.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 6","pages":"357-358"},"PeriodicalIF":78.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556712","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 : 2024-04-16DOI: 10.1038/s41568-024-00679-6
Naiara Perurena, Lisa Situ, Karen Cichowski
Although RAS was formerly considered undruggable, various agents that inhibit RAS or specific RAS oncoproteins have now been developed. Indeed, the importance of directly targeting RAS has recently been illustrated by the clinical success of mutant-selective KRAS inhibitors. Nevertheless, responses to these agents are typically incomplete and restricted to a subset of patients, highlighting the need to develop more effective treatments, which will likely require a combinatorial approach. Vertical strategies that target multiple nodes within the RAS pathway to achieve deeper suppression are being investigated and have precedence in other contexts. However, alternative strategies that co-target RAS and other therapeutic vulnerabilities have been identified, which may mitigate the requirement for profound pathway suppression. Regardless, the efficacy of any given approach will likely be dictated by genetic, epigenetic and tumour-specific variables. Here we discuss various combinatorial strategies to treat KRAS-driven cancers, highlighting mechanistic concepts that may extend to tumours harbouring other RAS mutations. Although many promising combinations have been identified, clinical responses will ultimately depend on whether a therapeutic window can be achieved and our ability to prospectively select responsive patients. Therefore, we must continue to develop and understand biologically diverse strategies to maximize our likelihood of success. In this Review, Cichowski and colleagues provide an overview of combinatorial strategies designed to treat RAS-driven cancers that are based on four concepts that include vertical pathway inhibition, co-targeting RAS and adaptive survival pathways, co-targeting downstream or converging pathways and capitalizing on other cancer-associated vulnerabilities.
{"title":"Combinatorial strategies to target RAS-driven cancers","authors":"Naiara Perurena, Lisa Situ, Karen Cichowski","doi":"10.1038/s41568-024-00679-6","DOIUrl":"10.1038/s41568-024-00679-6","url":null,"abstract":"Although RAS was formerly considered undruggable, various agents that inhibit RAS or specific RAS oncoproteins have now been developed. Indeed, the importance of directly targeting RAS has recently been illustrated by the clinical success of mutant-selective KRAS inhibitors. Nevertheless, responses to these agents are typically incomplete and restricted to a subset of patients, highlighting the need to develop more effective treatments, which will likely require a combinatorial approach. Vertical strategies that target multiple nodes within the RAS pathway to achieve deeper suppression are being investigated and have precedence in other contexts. However, alternative strategies that co-target RAS and other therapeutic vulnerabilities have been identified, which may mitigate the requirement for profound pathway suppression. Regardless, the efficacy of any given approach will likely be dictated by genetic, epigenetic and tumour-specific variables. Here we discuss various combinatorial strategies to treat KRAS-driven cancers, highlighting mechanistic concepts that may extend to tumours harbouring other RAS mutations. Although many promising combinations have been identified, clinical responses will ultimately depend on whether a therapeutic window can be achieved and our ability to prospectively select responsive patients. Therefore, we must continue to develop and understand biologically diverse strategies to maximize our likelihood of success. In this Review, Cichowski and colleagues provide an overview of combinatorial strategies designed to treat RAS-driven cancers that are based on four concepts that include vertical pathway inhibition, co-targeting RAS and adaptive survival pathways, co-targeting downstream or converging pathways and capitalizing on other cancer-associated vulnerabilities.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 5","pages":"316-337"},"PeriodicalIF":78.5,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140556988","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 : 2024-04-12DOI: 10.1038/s41568-024-00688-5
Daniela Senft
In a recent study published in Nature, Goto et al. explore mechanisms of immune evasion in early colorectal cancers and adenomas and identify SOX17 to be crucial for immune escape through suppression of interferon-γ signalling.
{"title":"Programming immune escape","authors":"Daniela Senft","doi":"10.1038/s41568-024-00688-5","DOIUrl":"10.1038/s41568-024-00688-5","url":null,"abstract":"In a recent study published in Nature, Goto et al. explore mechanisms of immune evasion in early colorectal cancers and adenomas and identify SOX17 to be crucial for immune escape through suppression of interferon-γ signalling.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 5","pages":"294-294"},"PeriodicalIF":78.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547527","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 : 2024-04-12DOI: 10.1038/s41568-024-00691-w
Gabrielle Brewer
In this recent study, He et al. establish that chronic stress promotes metastasis through stress-induced formation of neutrophil extracellular traps (NETs).
{"title":"NET-working under stress","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00691-w","DOIUrl":"10.1038/s41568-024-00691-w","url":null,"abstract":"In this recent study, He et al. establish that chronic stress promotes metastasis through stress-induced formation of neutrophil extracellular traps (NETs).","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 5","pages":"294-294"},"PeriodicalIF":78.5,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140547541","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 : 2024-04-11DOI: 10.1038/s41568-024-00681-y
Triantafyllia Karakousi, Tenny Mudianto, Amanda W. Lund
Lymphatic transport maintains homeostatic health and is necessary for immune surveillance, and yet lymphatic growth is often associated with solid tumour development and dissemination. Although tumour-associated lymphatic remodelling and growth were initially presumed to simply expand a passive route for regional metastasis, emerging research puts lymphatic vessels and their active transport at the interface of metastasis, tumour-associated inflammation and systemic immune surveillance. Here, we discuss active mechanisms through which lymphatic vessels shape their transport function to influence peripheral tissue immunity and the current understanding of how tumour-associated lymphatic vessels may both augment and disrupt antitumour immune surveillance. We end by looking forward to emerging areas of interest in the field of cancer immunotherapy in which lymphatic vessels and their transport function are likely key players: the formation of tertiary lymphoid structures, immune surveillance in the central nervous system, the microbiome, obesity and ageing. The lessons learnt support a working framework that defines the lymphatic system as a key determinant of both local and systemic inflammatory networks and thereby a crucial player in the response to cancer immunotherapy. Tumour-associated lymphatic growth and remodelling were once viewed as a passive means by which cancer cells could regionally spread to lymph nodes. However, recent data point to an active and contrasting role for lymphatic vessels and their transport in antitumour immune surveillance. In this Review, Karakousi et al. provide a working framework to define this role for the lymphatic system in tumour progression and present avenues for its therapeutic manipulation to improve cancer immunotherapy.
{"title":"Lymphatic vessels in the age of cancer immunotherapy","authors":"Triantafyllia Karakousi, Tenny Mudianto, Amanda W. Lund","doi":"10.1038/s41568-024-00681-y","DOIUrl":"10.1038/s41568-024-00681-y","url":null,"abstract":"Lymphatic transport maintains homeostatic health and is necessary for immune surveillance, and yet lymphatic growth is often associated with solid tumour development and dissemination. Although tumour-associated lymphatic remodelling and growth were initially presumed to simply expand a passive route for regional metastasis, emerging research puts lymphatic vessels and their active transport at the interface of metastasis, tumour-associated inflammation and systemic immune surveillance. Here, we discuss active mechanisms through which lymphatic vessels shape their transport function to influence peripheral tissue immunity and the current understanding of how tumour-associated lymphatic vessels may both augment and disrupt antitumour immune surveillance. We end by looking forward to emerging areas of interest in the field of cancer immunotherapy in which lymphatic vessels and their transport function are likely key players: the formation of tertiary lymphoid structures, immune surveillance in the central nervous system, the microbiome, obesity and ageing. The lessons learnt support a working framework that defines the lymphatic system as a key determinant of both local and systemic inflammatory networks and thereby a crucial player in the response to cancer immunotherapy. Tumour-associated lymphatic growth and remodelling were once viewed as a passive means by which cancer cells could regionally spread to lymph nodes. However, recent data point to an active and contrasting role for lymphatic vessels and their transport in antitumour immune surveillance. In this Review, Karakousi et al. provide a working framework to define this role for the lymphatic system in tumour progression and present avenues for its therapeutic manipulation to improve cancer immunotherapy.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 6","pages":"363-381"},"PeriodicalIF":78.5,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140545288","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}
{"title":"Routes to second cancers","authors":"Anna Dart","doi":"10.1038/s41568-024-00689-4","DOIUrl":"10.1038/s41568-024-00689-4","url":null,"abstract":"Sánchez-Guixé et al. investigated the possible routes to second malignancies in survivors of paediatric cancer by studying four such clinical cases.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 5","pages":"293-293"},"PeriodicalIF":78.5,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140541215","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 : 2024-04-08DOI: 10.1038/s41568-024-00680-z
Tong Xiao, Juyeun Lee, Timothy D. Gauntner, Maria Velegraki, Justin D. Lathia, Zihai Li
Sex differences are present across multiple non-reproductive organ cancers, with male individuals generally experiencing higher incidence of cancer with poorer outcomes. Although some mechanisms underlying these differences are emerging, the immunological basis is not well understood. Observations from clinical trials also suggest a sex bias in conventional immunotherapies with male individuals experiencing a more favourable response and female individuals experiencing more severe adverse events to immune checkpoint blockade. In this Perspective article, we summarize the major biological hallmarks underlying sex bias in immuno-oncology. We focus on signalling from sex hormones and chromosome-encoded gene products, along with sex hormone-independent and chromosome-independent epigenetic mechanisms in tumour and immune cells such as myeloid cells and T cells. Finally, we highlight opportunities for future studies on sex differences that integrate sex hormones and chromosomes and other emerging cancer hallmarks such as ageing and the microbiome to provide a more comprehensive view of how sex differences underlie the response in cancer that can be leveraged for more effective immuno-oncology approaches. Sex differences impact various non-reproductive organ cancers, often leading to higher cancer incidence and poorer outcomes in male individuals. In this Perspective article, Xiao, Lee et al. outline the biological factors contributing to sex bias in immuno-oncology, emphasizing the need for future research to offer a fuller understanding of sex disparities in cancer.
在多种非生殖器官癌症中都存在性别差异，男性癌症发病率通常较高，治疗效果较差。虽然这些差异的一些内在机制正在形成，但其免疫学基础尚不十分清楚。临床试验的观察结果也表明，常规免疫疗法存在性别偏差，男性患者对免疫检查点阻断疗法的反应更佳，而女性患者则会出现更严重的不良反应。在这篇 "视角 "文章中，我们总结了免疫肿瘤学中性别偏见的主要生物学特征。我们重点关注性激素和染色体编码基因产物的信号传导，以及肿瘤和免疫细胞（如骨髓细胞和 T 细胞）中不依赖于性激素和不依赖于染色体的表观遗传机制。最后，我们强调了未来研究性别差异的机会，这些研究将性激素、染色体和其他新出现的癌症特征（如老龄化和微生物组）结合在一起，从而更全面地了解性别差异如何成为癌症反应的基础，从而利用性别差异制定更有效的免疫肿瘤学方法。
{"title":"Hallmarks of sex bias in immuno-oncology: mechanisms and therapeutic implications","authors":"Tong Xiao, Juyeun Lee, Timothy D. Gauntner, Maria Velegraki, Justin D. Lathia, Zihai Li","doi":"10.1038/s41568-024-00680-z","DOIUrl":"10.1038/s41568-024-00680-z","url":null,"abstract":"Sex differences are present across multiple non-reproductive organ cancers, with male individuals generally experiencing higher incidence of cancer with poorer outcomes. Although some mechanisms underlying these differences are emerging, the immunological basis is not well understood. Observations from clinical trials also suggest a sex bias in conventional immunotherapies with male individuals experiencing a more favourable response and female individuals experiencing more severe adverse events to immune checkpoint blockade. In this Perspective article, we summarize the major biological hallmarks underlying sex bias in immuno-oncology. We focus on signalling from sex hormones and chromosome-encoded gene products, along with sex hormone-independent and chromosome-independent epigenetic mechanisms in tumour and immune cells such as myeloid cells and T cells. Finally, we highlight opportunities for future studies on sex differences that integrate sex hormones and chromosomes and other emerging cancer hallmarks such as ageing and the microbiome to provide a more comprehensive view of how sex differences underlie the response in cancer that can be leveraged for more effective immuno-oncology approaches. Sex differences impact various non-reproductive organ cancers, often leading to higher cancer incidence and poorer outcomes in male individuals. In this Perspective article, Xiao, Lee et al. outline the biological factors contributing to sex bias in immuno-oncology, emphasizing the need for future research to offer a fuller understanding of sex disparities in cancer.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 5","pages":"338-355"},"PeriodicalIF":78.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538323","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 : 2024-04-08DOI: 10.1038/s41568-024-00686-7
Kaile Wang
In this Tools of the Trade article, Kaile Wang describes the development and use of Arc-well, a high-throughput single-cell DNA sequencing method tailored to analyse archival formalin-fixed paraffin-embedded (FFPE) materials.
{"title":"Revealing genomic secrets of archival FFPE samples","authors":"Kaile Wang","doi":"10.1038/s41568-024-00686-7","DOIUrl":"10.1038/s41568-024-00686-7","url":null,"abstract":"In this Tools of the Trade article, Kaile Wang describes the development and use of Arc-well, a high-throughput single-cell DNA sequencing method tailored to analyse archival formalin-fixed paraffin-embedded (FFPE) materials.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 6","pages":"359-359"},"PeriodicalIF":78.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538584","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 : 2024-04-08DOI: 10.1038/s41568-024-00683-w
Christine Desmedt, Lisa A Carey
Metastatic cancer represents the main cause of death in patients with cancer. However, basic and translational research is hampered by the limited availability of metastatic samples. In this context, post-mortem tissue donation programmes represent a complementary and attractive solution. Here, we highlight the opportunities and challenges, and outline why we believe this represents a global effort. Metastatic cancer represents the main cause of death in patients with cancer, but metastasis research is hindered by the limited availability of metastatic samples. In this Comment, Desmedt and Carey highlight the opportunities and challenges of post-mortem tissue donation programmes, which represent a complementary and attractive solution to overcome many of the hurdles in metastasis research.
{"title":"Global post-mortem tissue donation programmes to accelerate cancer research","authors":"Christine Desmedt, Lisa A Carey","doi":"10.1038/s41568-024-00683-w","DOIUrl":"10.1038/s41568-024-00683-w","url":null,"abstract":"Metastatic cancer represents the main cause of death in patients with cancer. However, basic and translational research is hampered by the limited availability of metastatic samples. In this context, post-mortem tissue donation programmes represent a complementary and attractive solution. Here, we highlight the opportunities and challenges, and outline why we believe this represents a global effort. Metastatic cancer represents the main cause of death in patients with cancer, but metastasis research is hindered by the limited availability of metastatic samples. In this Comment, Desmedt and Carey highlight the opportunities and challenges of post-mortem tissue donation programmes, which represent a complementary and attractive solution to overcome many of the hurdles in metastasis research.","PeriodicalId":72,"journal":{"name":"Energy & Environmental Science","volume":"24 5","pages":"289-290"},"PeriodicalIF":78.5,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538359","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}
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