Nature Reviews Cancer最新文献

{"title":"When tumour cells get excited","authors":"Daniela Senft","doi":"10.1038/s41568-025-00808-9","DOIUrl":"10.1038/s41568-025-00808-9","url":null,"abstract":"A recent study published in Nature finds that neuroendocrine small-cell lung cancer (SCLC) cells exhibit electrical activity that directly drives tumour progression and metastasis and shows that they rely on oxidative phosphorylation to meet the high energy demand associated with these electrophysiological processes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"222-222"},"PeriodicalIF":72.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569362","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":"ALK in cancer: from function to therapeutic targeting","authors":"Claudia Voena, Chiara Ambrogio, Fabio Iannelli, Roberto Chiarle","doi":"10.1038/s41568-025-00797-9","DOIUrl":"https://doi.org/10.1038/s41568-025-00797-9","url":null,"abstract":"<p>Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase (RTK) that acts as an oncogenic driver in solid and haematological malignancies in both children and adults. Although ALK-expressing (ALK⁺) tumours show strong initial responses to the series of ALK inhibitors currently available, many patients will develop resistance. In this Review, we discuss recent advances in ALK oncogenic signalling, together with existing and promising new modalities to treat ALK-driven tumours, including currently approved ALK-directed therapies, namely tyrosine kinase inhibitors, and novel approaches such as ALK-specific immune therapies. Although ALK inhibitors have changed the management and clinical history of ALK⁺ tumours, they are still insufficient to cure most of the patients. Therefore, more effort is needed to further improve outcomes and prevent the tumour resistance, recurrence and metastatic spread that many patients with ALK⁺ tumours experience. Here, we outline how a multipronged approach directed against ALK and other essential pathways that sustain the persistence of ALK⁺ tumours, together with potent or specific immunotherapies, could achieve this goal. We envision that the lessons learned from treating ALK⁺ tumours in the clinic could ultimately accelerate the implementation of innovative combination therapies to treat tumours driven by other tyrosine kinases or oncogenes with similar properties.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"67 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143569431","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":"PROTACing against liver cancer","authors":"Anna Dart","doi":"10.1038/s41568-025-00805-y","DOIUrl":"10.1038/s41568-025-00805-y","url":null,"abstract":"Yang et al. developed a proteolysis-targeting chimera (PROTAC) 753b, which targets BCL-xL and BCL-2 to the E3 ubiquitin ligase VHL, and showed that it removed senescent cells specifically from the liver, reducing the progression of chronic metabolic liver disease to liver cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"223-223"},"PeriodicalIF":72.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560616","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":"We cannot ignore the cancer risks of wildfires","authors":"Scott Weichenthal","doi":"10.1038/s41568-025-00804-z","DOIUrl":"10.1038/s41568-025-00804-z","url":null,"abstract":"Wildfires release a range of known human carcinogens and tend to occur in the same regions each year. As a result, long-term exposures to wildfire pollutants are a concern and will probably increase cancer risk in exposed populations. Actionable solutions are available to reduce exposures and mitigate these risks. Wildfires emit carcinogenic pollutants, raising long-term cancer risks in affected populations. In this Comment, Weichenthal highlights these concerns and outlines actionable solutions to reduce exposure and mitigate risks.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"219-220"},"PeriodicalIF":72.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545877","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":"A machine learning toolkit for subtyping cancer in existing and new datasets","authors":"Jordan Lee","doi":"10.1038/s41568-025-00802-1","DOIUrl":"https://doi.org/10.1038/s41568-025-00802-1","url":null,"abstract":"In this Tools of the Trade article, Jordan Lee describes the development and use of the Tumor Molecular Pathology (TMP) toolkit, a cancer subtyping tool that can assign TCGA molecular subtypes to new, independent non-TCGA datasets.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"18 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143545875","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":"Genomic and fragmentomic landscapes of cell-free DNA for early cancer detection","authors":"Daniel C. Bruhm, Nicholas A. Vulpescu, Zachariah H. Foda, Jillian Phallen, Robert B. Scharpf, Victor E. Velculescu","doi":"10.1038/s41568-025-00795-x","DOIUrl":"https://doi.org/10.1038/s41568-025-00795-x","url":null,"abstract":"<p>Genomic analyses of cell-free DNA (cfDNA) in plasma are enabling noninvasive blood-based biomarker approaches to cancer detection and disease monitoring. Current approaches for identification of circulating tumour DNA typically use targeted tumour-specific mutations or methylation analyses. An emerging approach is based on the recognition of altered genome-wide cfDNA fragmentation in patients with cancer. Recent studies have revealed a multitude of characteristics that can affect the compendium of cfDNA fragments across the genome, collectively called the ‘cfDNA fragmentome’. These changes result from genomic, epigenomic, transcriptomic and chromatin states of an individual and affect the size, position, coverage, mutation, structural and methylation characteristics of cfDNA. Identifying and monitoring these changes has the potential to improve early detection of cancer, especially using highly sensitive multi-feature machine learning approaches that would be amenable to broad use in populations at increased risk. This Review highlights the rapidly evolving field of genome-wide analyses of cfDNA characteristics, their comparison to existing cfDNA methods, and recent related innovations at the intersection of large-scale sequencing and artificial intelligence. As the breadth of clinical applications of cfDNA fragmentome methods have enormous public health implications for cancer screening and personalized approaches for clinical management of patients with cancer, we outline the challenges and opportunities ahead.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"147 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143538604","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 treatments accelerate ageing","authors":"Marco Demaria","doi":"10.1038/s41568-025-00801-2","DOIUrl":"https://doi.org/10.1038/s41568-025-00801-2","url":null,"abstract":"Advancements in cancer treatment have led to a growing population of cancer survivors worldwide, who often experience premature onset of age-related conditions. Understanding the molecular and cellular basis of the long-term consequences of cancer treatment is essential for developing interventions to mitigate their adverse effects. While cancer treatments are essential for patient survival, they often induce premature ageing-related conditions in survivors. In this Comment, Demaria outlines how understanding the underlying molecular mechanisms of this is crucial for developing integrated strategies to improve long-term health outcomes in survivors.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"66 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143506814","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":"Detecting somatic mutations in single-cell data with SComatic","authors":"Tim H. H. Coorens","doi":"10.1038/s41568-025-00799-7","DOIUrl":"10.1038/s41568-025-00799-7","url":null,"abstract":"In this Tool of the Trade article, Tim Coorens describes the development of SComatic, an algorithm enabling the detection of somatic mutations in single-cell RNA- or ATAC-sequencing data, and its use to study lineage relations and mutational signatures.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"221-221"},"PeriodicalIF":72.5,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485853","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":"Translating premalignant biology to accelerate non-small-cell lung cancer interception","authors":"Sarah A. Mazzilli, Zahraa Rahal, Maral J. Rouhani, Sam M. Janes, Humam Kadara, Steven M. Dubinett, Avrum E. Spira","doi":"10.1038/s41568-025-00791-1","DOIUrl":"https://doi.org/10.1038/s41568-025-00791-1","url":null,"abstract":"<p>Over the past decade, substantial progress has been made in the development of targeted and immune-based therapies for patients with advanced non-small-cell lung cancer. To further improve outcomes for patients with lung cancer, identifying and intercepting disease at the earliest and most curable stages are crucial next steps. With the recent implementation of low-dose computed tomography scan screening in populations at high risk, there is an emerging unmet need for new diagnostic, prognostic and therapeutic tools to help treat patients suspected of harbouring premalignant lesions and minimally invasive non-small-cell lung cancer. Continued advances in the identification of the earliest drivers of lung carcinogenesis are poised to address these unmet needs. Employing multimodal approaches to chart the temporal and spatial maps of the molecular events driving lung premalignant lesion progression will refine our understanding of early carcinogenesis. Elucidating the molecular drivers of premalignancy is critical to the development of biomarkers to detect those incubating a premalignant lesion, to stratify risk for progression to invasive cancer and to identify novel therapeutic targets to intercept that process. In this Review, we summarize emerging insights into the earliest cellular and molecular events associated with lung squamous and adenocarcinoma carcinogenesis and highlight the growing opportunity for translating these insights into clinical tools for early detection and disease interception to transform the outcomes for those at risk for lung cancer.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"31 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143485525","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":"Defining a ‘cells to society’ research framework for appendiceal tumours","authors":"Andreana N. Holowatyj,&nbsp;Michael J. Overman,&nbsp;Konstantinos I. Votanopoulos,&nbsp;Andrew M. Lowy,&nbsp;Patrick Wagner,&nbsp;Mary K. Washington,&nbsp;Cathy Eng,&nbsp;Wai Chin Foo,&nbsp;Richard M. Goldberg,&nbsp;Mojgan Hosseini,&nbsp;Kamran Idrees,&nbsp;Douglas B. Johnson,&nbsp;Ardaman Shergill,&nbsp;Erin Ward,&nbsp;Nicholas C. Zachos,&nbsp;Deborah Shelton,&nbsp;on behalf of Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation","doi":"10.1038/s41568-024-00788-2","DOIUrl":"10.1038/s41568-024-00788-2","url":null,"abstract":"Tumours of the appendix — a vestigial digestive organ attached to the colon — are rare. Although we estimate that around 3,000 new appendiceal cancer cases are diagnosed annually in the USA, the challenges of accurately diagnosing and identifying this tumour type suggest that this number may underestimate true population incidence. In the current absence of disease-specific screening and diagnostic imaging modalities, or well-established risk factors, the incidental discovery of appendix tumours is often prompted by acute presentations mimicking appendicitis or when the tumour has already spread into the abdominal cavity — wherein the potential misclassification of appendiceal tumours as malignancies of the colon and ovaries also increases. Notwithstanding these diagnostic difficulties, our understanding of appendix carcinogenesis has advanced in recent years. However, there persist considerable challenges to accelerating the pace of research discoveries towards the path to improved treatments and cures for patients with this group of orphan malignancies. The premise of this Expert Recommendation article is to discuss the current state of the field, to delineate unique challenges for the study of appendiceal tumours, and to propose key priority research areas that will deliver a more complete picture of appendix carcinogenesis and metastasis. The Appendix Cancer Pseudomyxoma Peritonei (ACPMP) Research Foundation Scientific Think Tank delivered a consensus of core research priorities for appendiceal tumours that are poised to be ground-breaking and transformative for scientific discovery and innovation. On the basis of these six research areas, here, we define the first ‘cells to society’ research framework for appendix tumours. In this Expert Recommendation, Holowatyj et al. cover the current state of the field in appendiceal cancer, including the distinct challenges involved in studying this rare tumour type, and propose a conceptual research framework to facilitate discoveries that will advance knowledge of appendix carcinogenesis and metastasis to deliver better outcomes for patients.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"293-315"},"PeriodicalIF":72.5,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451476","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}