{"title":"Chromothripsis in cancer.","authors":"Milena Simovic-Lorenz, Aurélie Ernst","doi":"10.1038/s41568-024-00769-5","DOIUrl":"https://doi.org/10.1038/s41568-024-00769-5","url":null,"abstract":"<p><p>Chromothripsis is a mutational phenomenon in which a single catastrophic event generates extensive rearrangements of one or a few chromosomes. This extreme form of genome instability has been detected in 30-50% of cancers. Studies conducted in the past few years have uncovered insights into how chromothripsis arises and deciphered some of the cellular and molecular consequences of chromosome shattering. This Review discusses the defining features of chromothripsis and describes its prevalence across different cancer types as indicated by the manifestations of chromothripsis detected in human cancer samples. The different mechanistic models of chromothripsis, derived from in vitro systems that enable causal inference through experimental manipulation, are discussed in detail. The contribution of chromothripsis to cancer development, the selective advantages that cancer cells might gain from chromothripsis, the evolutionary trajectories of chromothriptic tumours, and the potential vulnerabilities and therapeutic opportunities presented by chromothriptic cells are also highlighted.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":" ","pages":""},"PeriodicalIF":72.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639389","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":"Breast milk for breast cancer detection","authors":"Gabrielle Brewer","doi":"10.1038/s41568-023-00636-9","DOIUrl":"10.1038/s41568-023-00636-9","url":null,"abstract":"Pregnancy-associated breast cancers are typically diagnosed at more advanced stages than other breast cancers. Recently, Saura et al. developed a non-invasive screening method using breast milk to diagnose patients prior to tumour detection by imaging.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 12","pages":"801-801"},"PeriodicalIF":78.5,"publicationDate":"2023-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41237054","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":"Stem-like exhausted and memory CD8+ T cells in cancer","authors":"Thomas Gebhardt, Simone L. Park, Ian A. Parish","doi":"10.1038/s41568-023-00615-0","DOIUrl":"10.1038/s41568-023-00615-0","url":null,"abstract":"T cells can acquire a broad spectrum of differentiation states following activation. At the extreme ends of this continuum are short-lived cells equipped with effector machinery and more quiescent, long-lived cells with heightened proliferative potential and stem cell-like developmental plasticity. The latter encompass stem-like exhausted T cells and memory T cells, both of which have recently emerged as key determinants of cancer immunity and response to immunotherapy. Here, we discuss key similarities and differences in the regulation and function of stem-like exhausted CD8+ T cells and memory CD8+ T cells, and consider their context-specific contributions to protective immunity in diverse outcomes of cancer, including tumour escape, long-term control and eradication. Finally, we emphasize how recent advances in the understanding of the molecular regulation of stem-like exhausted T cells and memory T cells are being explored for clinical benefit in cancer immunotherapies such as checkpoint inhibition, adoptive cell therapy and vaccination. T cells can acquire a broad spectrum of differentiation states following activation; certain subtypes of T cells have emerged as key determinants of cancer immunity and response to immunotherapies. Here, Gebhardt, Park and Parish discuss the phenotypic and functional variation of stem-like exhausted CD8+ T cells and memory CD8+ T cells, and how it contributes to their roles in immune escape and cancer outcome.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 11","pages":"780-798"},"PeriodicalIF":78.5,"publicationDate":"2023-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41206535","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":"Transfer RNAs as dynamic and critical regulators of cancer progression","authors":"Alexandra M. Pinzaru, Sohail F. Tavazoie","doi":"10.1038/s41568-023-00611-4","DOIUrl":"10.1038/s41568-023-00611-4","url":null,"abstract":"Transfer RNAs (tRNAs) have been historically viewed as non-dynamic adaptors that decode the genetic code into proteins. Recent work has uncovered dynamic regulatory roles for these fascinating molecules. Advances in tRNA detection methods have revealed that specific tRNAs can become modulated upon DNA copy number and chromatin alterations and can also be perturbed by oncogenic signalling and transcriptional regulators in cancer cells or the tumour microenvironment. Such alterations in the levels of specific tRNAs have been shown to causally impact cancer progression, including metastasis. Moreover, sequencing methods have identified tRNA-derived small RNAs that influence various aspects of cancer progression, such as cell proliferation and invasion, and could serve as diagnostic and prognostic biomarkers or putative therapeutic targets in various cancers. Finally, there is accumulating evidence, including from genetic models, that specific tRNA synthetases — the enzymes responsible for charging tRNAs with amino acids — can either promote or suppress tumour formation. In this Review, we provide an overview of how deregulation of tRNAs influences cancer formation and progression. Transfer RNAs have long been known as static adaptors that translate the genetic code but are now emerging as dynamic regulators in health and disease, including cancer. This Review discusses how the deregulation of the tRNA pool, tRNA-derived small RNAs and tRNA synthetases impacts tumour initiation and progression.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 11","pages":"746-761"},"PeriodicalIF":78.5,"publicationDate":"2023-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41183133","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":"Prime editing GEMMs to model cancer mutations","authors":"Nicolas Mathey-Andrews","doi":"10.1038/s41568-023-00627-w","DOIUrl":"10.1038/s41568-023-00627-w","url":null,"abstract":"In this Tool of the Trade article, Nicolas Mathey-Andrews describes the generation and use of a prime editor mouse that enables in vivo modelling of the multitude of cancer alleles found in human tumours.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 1","pages":"2-2"},"PeriodicalIF":78.5,"publicationDate":"2023-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105026","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":"Enhanced transposable elements","authors":"Gabrielle Brewer","doi":"10.1038/s41568-023-00631-0","DOIUrl":"10.1038/s41568-023-00631-0","url":null,"abstract":"Karttunen et al. identify the contribution of transposable elements to gene regulatory function in colorectal and liver cancer cell lines.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 11","pages":"729-729"},"PeriodicalIF":78.5,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105025","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":"Tertiary lymphoid structures as hubs of antitumour immunity","authors":"Gabriela Sarti Kinker, Tiago da Silva Medina","doi":"10.1038/s41568-023-00626-x","DOIUrl":"10.1038/s41568-023-00626-x","url":null,"abstract":"In this Journal Club, Kinker & Medina discuss a study showing the role of tumour-associated tertiary lymphoid structures in improving immunotherapy response and overall survival in patients with melanoma.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 12","pages":"803-803"},"PeriodicalIF":78.5,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41143386","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":"Synaptic activity promotes melanoma formation","authors":"Daniela Senft","doi":"10.1038/s41568-023-00629-8","DOIUrl":"10.1038/s41568-023-00629-8","url":null,"abstract":"In a recent study, Tagore et al. find that the formation of synapse-like structures that serve to transfer GABA between premalignant melanocytes and keratinocytes promotes melanoma initiation by the BRAFV600E oncogene.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 11","pages":"728-728"},"PeriodicalIF":78.5,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41119902","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":"Computing brain metastasis impact","authors":"Daniela Senft","doi":"10.1038/s41568-023-00630-1","DOIUrl":"10.1038/s41568-023-00630-1","url":null,"abstract":"In a recent study, Sanchez-Aguilera, Masmudi-Martín et al. find that a molecular program explains the cognitive impairment often seen in patients with brain metastasis, challenging the prevailing paradigm of the tumour mass being the sole cause of altered brain function.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 11","pages":"729-729"},"PeriodicalIF":78.5,"publicationDate":"2023-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41153578","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":"Harnessing the influenza virus to fight cancer","authors":"Dezhong Ji","doi":"10.1038/s41568-023-00625-y","DOIUrl":"10.1038/s41568-023-00625-y","url":null,"abstract":"In this Tools of the Trade article, Dezhong Ji describes the development and use of a chimeric antigenic peptide influenza virus (CAP-Flu) system as a cancer vaccine strategy to promote tumour-infiltrating T cell activation in lung metastasis.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 1","pages":"1-1"},"PeriodicalIF":78.5,"publicationDate":"2023-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41146796","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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