Pub Date : 2024-11-15DOI: 10.1038/s41568-024-00769-5
Milena Simovic-Lorenz, Aurélie Ernst
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.
{"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}
Pub Date : 2023-10-23DOI: 10.1038/s41568-023-00640-z
Hongcheng Mai
In this Tools of the Trade article, Hongcheng Mai describes the development of wildDISCO, an approach for whole-body immunolabelling, optical clearing and imaging in mice.
在这篇 "贸易工具"（Tools of the Trade）文章中，Hongcheng Mai 介绍了 wildDISCO 的开发情况，这是一种用于小鼠全身免疫标记、光学清除和成像的方法。
{"title":"wildDISCO: HD whole-body imaging","authors":"Hongcheng Mai","doi":"10.1038/s41568-023-00640-z","DOIUrl":"10.1038/s41568-023-00640-z","url":null,"abstract":"In this Tools of the Trade article, Hongcheng Mai describes the development of wildDISCO, an approach for whole-body immunolabelling, optical clearing and imaging in mice.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 1","pages":"1-1"},"PeriodicalIF":78.5,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691574","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 : 2023-10-23DOI: 10.1038/s41568-023-00638-7
Doratha Byrd, Patricia Wolf
People from minority racial and ethnic groups continue to experience disproportionate cancer incidences and cancer-associated mortality rates. In this Comment, Byrd and Wolf explore the contribution of non-medical factors to the composition of the gut microbiome, and how this may be an actionable target for reducing these disparities.
{"title":"The microbiome as a determinant of racial and ethnic cancer disparities","authors":"Doratha Byrd, Patricia Wolf","doi":"10.1038/s41568-023-00638-7","DOIUrl":"10.1038/s41568-023-00638-7","url":null,"abstract":" People from minority racial and ethnic groups continue to experience disproportionate cancer incidences and cancer-associated mortality rates. In this Comment, Byrd and Wolf explore the contribution of non-medical factors to the composition of the gut microbiome, and how this may be an actionable target for reducing these disparities.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 2","pages":"89-90"},"PeriodicalIF":78.5,"publicationDate":"2023-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691573","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 : 2023-10-19DOI: 10.1038/s41568-023-00623-0
Chandrayee Ghosh, Jiangnan Hu, Electron Kebebew
Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1–2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately one third of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT–β-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP–protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutations and the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome. Adrenocortical carcinoma is a rare endocrine cancer with a dismal survival rate and limited therapeutic options. This Review outlines the recent advances that have been made in the understanding of the molecular basis of adrenocortical carcinoma and what this means for the diagnosis and treatment of patients with this cancer type.
肾上腺皮质癌是一种罕见的恶性肿瘤，全球每年发病率为每100万人中有1-2例，5年生存率为
{"title":"Advances in translational research of the rare cancer type adrenocortical carcinoma","authors":"Chandrayee Ghosh, Jiangnan Hu, Electron Kebebew","doi":"10.1038/s41568-023-00623-0","DOIUrl":"10.1038/s41568-023-00623-0","url":null,"abstract":"Adrenocortical carcinoma is a rare malignancy with an annual worldwide incidence of 1–2 cases per 1 million and a 5-year survival rate of <60%. Although adrenocortical carcinoma is rare, such rare cancers account for approximately one third of patients diagnosed with cancer annually. In the past decade, there have been considerable advances in understanding the molecular basis of adrenocortical carcinoma. The genetic events associated with adrenocortical carcinoma in adults are distinct from those of paediatric cases, which are often associated with germline or somatic TP53 mutations and have a better prognosis. In adult primary adrenocortical carcinoma, the main somatic genetic alterations occur in genes that encode proteins involved in the WNT–β-catenin pathway, cell cycle and p53 apoptosis pathway, chromatin remodelling and telomere maintenance pathway, cAMP–protein kinase A (PKA) pathway or DNA transcription and RNA translation pathways. Recently, integrated molecular studies of adrenocortical carcinomas, which have characterized somatic mutations and the methylome as well as gene and microRNA expression profiles, have led to a molecular classification of these tumours that can predict prognosis and have helped to identify new therapeutic targets. In this Review, we summarize these recent translational research advances in adrenocortical carcinoma, which it is hoped could lead to improved patient diagnosis, treatment and outcome. Adrenocortical carcinoma is a rare endocrine cancer with a dismal survival rate and limited therapeutic options. This Review outlines the recent advances that have been made in the understanding of the molecular basis of adrenocortical carcinoma and what this means for the diagnosis and treatment of patients with this cancer type.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"23 12","pages":"805-824"},"PeriodicalIF":78.5,"publicationDate":"2023-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49679953","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 : 2023-10-17DOI: 10.1038/s41568-023-00636-9
Gabrielle Brewer
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.
{"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}
Pub Date : 2023-10-11DOI: 10.1038/s41568-023-00615-0
Thomas Gebhardt, Simone L. Park, Ian A. Parish
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.
{"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}
Pub Date : 2023-10-09DOI: 10.1038/s41568-023-00611-4
Alexandra M. Pinzaru, Sohail F. Tavazoie
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.
{"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}
Pub Date : 2023-09-28DOI: 10.1038/s41568-023-00627-w
Nicolas Mathey-Andrews
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.
{"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}
Pub Date : 2023-09-27DOI: 10.1038/s41568-023-00631-0
Gabrielle Brewer
Karttunen et al. identify the contribution of transposable elements to gene regulatory function in colorectal and liver cancer cell lines.
Karttunen 等人确定了转座元件对结直肠癌和肝癌细胞系基因调控功能的贡献。
{"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}
Pub Date : 2023-09-27DOI: 10.1038/s41568-023-00626-x
Gabriela Sarti Kinker, Tiago da Silva Medina
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.
{"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}
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