{"title":"Extrachromosomal DNA in cancer","authors":"Xiaowei Yan, Paul Mischel, Howard Chang","doi":"10.1038/s41568-024-00669-8","DOIUrl":"10.1038/s41568-024-00669-8","url":null,"abstract":"Extrachromosomal DNA (ecDNA) has recently been recognized as a major contributor to cancer pathogenesis that is identified in most cancer types and is associated with poor outcomes. When it was discovered over 60 years ago, ecDNA was considered to be rare, and its impact on tumour biology was not well understood. The application of modern imaging and computational techniques has yielded powerful new insights into the importance of ecDNA in cancer. The non-chromosomal inheritance of ecDNA during cell division results in high oncogene copy number, intra-tumoural genetic heterogeneity and rapid tumour evolution that contributes to treatment resistance and shorter patient survival. In addition, the circular architecture of ecDNA results in altered patterns of gene regulation that drive elevated oncogene expression, potentially enabling the remodelling of tumour genomes. The generation of clusters of ecDNAs, termed ecDNA hubs, results in interactions between enhancers and promoters in trans, yielding a new paradigm in oncogenic transcription. In this Review, we highlight the rapid advancements in ecDNA research, providing new insights into ecDNA biogenesis, maintenance and transcription and its role in promoting tumour heterogeneity. To conclude, we delve into a set of unanswered questions whose answers will pave the way for the development of ecDNA targeted therapeutic approaches. Extrachromosomal DNA (ecDNA) is now accepted as a major contributor to cancer pathogenesis. In this Review, Yan, Mischel and Chang highlight the recent advancements in ecDNA research, providing new insights into the biogenesis and maintenance of ecDNA, as well as its role in altering gene expression and promoting tumour heterogeneity.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 4","pages":"261-273"},"PeriodicalIF":78.5,"publicationDate":"2024-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972759","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}
Kilan C. Ashad-Bishop, Onyinye D. Balogun, Runcie C. W. Chidebe, Leah M. Cook, Christina Towers
{"title":"Black voices in cancer research and oncology","authors":"Kilan C. Ashad-Bishop, Onyinye D. Balogun, Runcie C. W. Chidebe, Leah M. Cook, Christina Towers","doi":"10.1038/s41568-023-00662-7","DOIUrl":"10.1038/s41568-023-00662-7","url":null,"abstract":"Over the past few years, there has been an increasing realization that we need a more equal, diverse and inclusive culture for truly successful cancer research to happen. Moreover, that research itself must be relevant to and engage a diverse patient population to achieve effective cancer care. Now is the time for action, so how do we attract and retain more diverse researchers to the cancer community, and how do we begin to close the gap in cancer disparities. We asked five Black cancer researchers and clinicians to present their ideas for bringing about positive change. In this Viewpoint article, we asked five Black cancer researchers and clinicians to present their ideas on how we can attract and retain more diverse researchers to the cancer community and how we begin to close the gap in cancer disparities.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 4","pages":"235-239"},"PeriodicalIF":78.5,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139906137","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":"Beyond genetics: driving cancer with the tumour microenvironment behind the wheel","authors":"Shaopeng Yuan, Jorge Almagro, Elaine Fuchs","doi":"10.1038/s41568-023-00660-9","DOIUrl":"10.1038/s41568-023-00660-9","url":null,"abstract":"Cancer has long been viewed as a genetic disease of cumulative mutations. This notion is fuelled by studies showing that ageing tissues are often riddled with clones of complex oncogenic backgrounds coexisting in seeming harmony with their normal tissue counterparts. Equally puzzling, however, is how cancer cells harbouring high mutational burden contribute to normal, tumour-free mice when allowed to develop within the confines of healthy embryos. Conversely, recent evidence suggests that adult tissue cells expressing only one or a few oncogenes can, in some contexts, generate tumours exhibiting many of the features of a malignant, invasive cancer. These disparate observations are difficult to reconcile without invoking environmental cues triggering epigenetic changes that can either dampen or drive malignant transformation. In this Review, we focus on how certain oncogenes can launch a two-way dialogue of miscommunication between a stem cell and its environment that can rewire downstream events non-genetically and skew the morphogenetic course of the tissue. We review the cells and molecules of and the physical forces acting in the resulting tumour microenvironments that can profoundly affect the behaviours of transformed cells. Finally, we discuss possible explanations for the remarkable diversity in the relative importance of mutational burden versus tumour microenvironment and its clinical relevance. In their Review article, Fuchs and colleagues discuss how a single or a few mutations in adult cells can lead to invasive cancers without a high mutational burden, demonstrating that non-genetic factors induce the epigenetic changes necessary for tumorigenesis.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 4","pages":"274-286"},"PeriodicalIF":78.5,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723459","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}
Jessica Galloway-Peña, Iliyan D. Iliev, Florencia McAllister
{"title":"Fungi in cancer","authors":"Jessica Galloway-Peña, Iliyan D. Iliev, Florencia McAllister","doi":"10.1038/s41568-024-00665-y","DOIUrl":"10.1038/s41568-024-00665-y","url":null,"abstract":"Both the gut and the tumour microbiome are now established as crucial regulators of cancer phenotypes and have been implicated in cancer initiation, progression and therapy response. Although the role of bacteria in these processes is beginning to be unravelled, the relevance of fungi is only just emerging. In this Viewpoint, we asked experts to discuss the current knowledge on the mycobiome–cancer connection and share their opinion on how to best solve open questions. In this Viewpoint article, we asked three scientists working on the cancer mycobiome to provide their opinions on advancements and challenges and what the future holds for this exciting field of cancer research.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 5","pages":"295-298"},"PeriodicalIF":78.5,"publicationDate":"2024-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139723460","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":"Discovering new drivers of cancer aneuploidy","authors":"Juliann Shih","doi":"10.1038/s41568-024-00671-0","DOIUrl":"10.1038/s41568-024-00671-0","url":null,"abstract":"In this Tools of the Trade, Juliann Shih describes the development of BISCUT, which detects genomic loci that are subject to fitness advantages or disadvantages by interrogating the length distributions of partial somatic copy-number alterations to enable the discovery of new drivers of aneuploidy in cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 4","pages":"229-229"},"PeriodicalIF":78.5,"publicationDate":"2024-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712664","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":"Cancer burden in low-income and middle-income countries","authors":"Sharmila Anandasabapathy, Chite Asirwa, Surbhi Grover, Chemtai Mungo","doi":"10.1038/s41568-023-00659-2","DOIUrl":"10.1038/s41568-023-00659-2","url":null,"abstract":"As cancer detection rates and therapy successes increase in high-income countries, it is predicted that over the next decade more than 75% of cancer-related deaths will occur in low-income and middle-income countries. Sub-Saharan Africa, which contains many of these countries, is currently unprepared with inadequate screening and detection methods, treatment and palliative care capacity. In this Viewpoint, we asked experts to discuss this burden and what is needed to alleviate it. In this Viewpoint, we asked four experts to discuss the increasing burden of cancer in low- and middle-income countries; they explore the changes that are necessary to improve cancer diagnosis, prevention and treatment within these nations.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 3","pages":"167-170"},"PeriodicalIF":78.5,"publicationDate":"2024-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707368","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":"Nanoreceptors take down mutant p53","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00675-w","DOIUrl":"10.1038/s41568-024-00675-w","url":null,"abstract":"Mutant gain-of-function p53 is commonly found in human cancers. Huang, Cao, Qian et al. developed and validated the use of multifunctional biomimetic nanoreceptors that bind to and promote the degradation of mutant p53 as a cancer therapy.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 3","pages":"164-164"},"PeriodicalIF":78.5,"publicationDate":"2024-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139695741","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":"Inferring cancer metabolism from gene-expression data","authors":"Vakul Mohanty","doi":"10.1038/s41568-024-00670-1","DOIUrl":"10.1038/s41568-024-00670-1","url":null,"abstract":"In this Tools of the Trade article, Vakul Mohanty describes the development and use of METAFlux, a computational framework that infers metabolic flux from bulk and single-cell RNA-sequencing data.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 4","pages":"230-230"},"PeriodicalIF":78.5,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139692434","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":"Multiplex protein imaging in tumour biology","authors":"Natalie de Souza, Shan Zhao, Bernd Bodenmiller","doi":"10.1038/s41568-023-00657-4","DOIUrl":"10.1038/s41568-023-00657-4","url":null,"abstract":"Tissue imaging has become much more colourful in the past decade. Advances in both experimental and analytical methods now make it possible to image protein markers in tissue samples in high multiplex. The ability to routinely image 40–50 markers simultaneously, at single-cell or subcellular resolution, has opened up new vistas in the study of tumour biology. Cellular phenotypes, interaction, communication and spatial organization have become amenable to molecular-level analysis, and application to patient cohorts has identified clinically relevant cellular and tissue features in several cancer types. Here, we review the use of multiplex protein imaging methods to study tumour biology, discuss ongoing attempts to combine these approaches with other forms of spatial omics, and highlight challenges in the field. In this Review, de Souza et al. discuss how advances in the ability to image protein markers at high-plex, at single-cell and even subcellular resolution, are expanding our understanding of tumour biology and clinical outcomes, and outline the future promise of combining such multiplex protein imaging methods with other forms of spatial omics.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 3","pages":"171-191"},"PeriodicalIF":78.5,"publicationDate":"2024-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139689202","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":"Finding the needle in the haystack","authors":"Daniela Senft","doi":"10.1038/s41568-024-00673-y","DOIUrl":"10.1038/s41568-024-00673-y","url":null,"abstract":"Goddard et al. report that disseminated tumour cells evade T cell immunity due to their relative scarcity, which decreases the likelihood of T cell–tumour cell interactions.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 3","pages":"163-163"},"PeriodicalIF":78.5,"publicationDate":"2024-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139660025","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}
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
