{"title":"Too much of a good thing","authors":"Anna Dart","doi":"10.1038/s41568-024-00698-3","DOIUrl":"10.1038/s41568-024-00698-3","url":null,"abstract":"Dias et al. have shown that intentional further activation of oncogenic signalling rather than its inhibition represents an alternative strategy leading to colorectal cancer cell death with tumour suppressive acquired resistance.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"360-360"},"PeriodicalIF":78.5,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140817818","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}
{"title":"Using the tumour microenvironment to improve therapy efficacy","authors":"Zuzana Tatarova","doi":"10.1038/s41568-024-00693-8","DOIUrl":"10.1038/s41568-024-00693-8","url":null,"abstract":"In this Tools of the Trade article, Zuzana Tatarova describes the development of MIMA, an integrated analytical platform providing the quantitative information on tumour microenvironment drug responses required for effective treatment design.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 7","pages":"444-444"},"PeriodicalIF":72.5,"publicationDate":"2024-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140648623","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}
{"title":"Investigating immune cells across time in vivo","authors":"Daniel Kirschenbaum","doi":"10.1038/s41568-024-00692-9","DOIUrl":"10.1038/s41568-024-00692-9","url":null,"abstract":"In this Tools of the Trade article, Daniel Kirschenbaum describes the development of Zman-seq and its utility for capturing dynamic changes in cellular state within single-cell RNA sequencing data.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 6","pages":"359-359"},"PeriodicalIF":78.5,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140632349","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}
{"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":19055,"journal":{"name":"Nature Reviews Cancer","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":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":19055,"journal":{"name":"Nature Reviews Cancer","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":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":19055,"journal":{"name":"Nature Reviews Cancer","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":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"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":19055,"journal":{"name":"Nature Reviews Cancer","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":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Triantafyllia Karakousi, Tenny Mudianto, Amanda W. Lund
{"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":19055,"journal":{"name":"Nature Reviews Cancer","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":"医学","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":19055,"journal":{"name":"Nature Reviews Cancer","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":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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