Pub Date : 2025-08-08DOI: 10.1038/s41568-025-00866-z
Anna Dart
Lyons et al. explored the rules of specificity and function for condensates formed by oncogenic fusion proteins, and identified a common molecular signature in these oncoproteins that compartmentalizes RNA polymerase II to confer an increase in gene activation and consequent cancer phenotypes.
{"title":"Rules of partitioning","authors":"Anna Dart","doi":"10.1038/s41568-025-00866-z","DOIUrl":"10.1038/s41568-025-00866-z","url":null,"abstract":"Lyons et al. explored the rules of specificity and function for condensates formed by oncogenic fusion proteins, and identified a common molecular signature in these oncoproteins that compartmentalizes RNA polymerase II to confer an increase in gene activation and consequent cancer phenotypes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 9","pages":"656-656"},"PeriodicalIF":66.8,"publicationDate":"2025-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144797077","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 : 2025-08-07DOI: 10.1038/s41568-025-00862-3
Daniela Senft
In a recent study published in Nature, Liu, Wang, et al. investigate the mechanisms underlying cytarabine-induced neurotoxicity and provide a mechanistic explanation for the differing neurotoxicity profiles of other nucleoside analogues, such as gemcitabine.
{"title":"Same same but different","authors":"Daniela Senft","doi":"10.1038/s41568-025-00862-3","DOIUrl":"10.1038/s41568-025-00862-3","url":null,"abstract":"In a recent study published in Nature, Liu, Wang, et al. investigate the mechanisms underlying cytarabine-induced neurotoxicity and provide a mechanistic explanation for the differing neurotoxicity profiles of other nucleoside analogues, such as gemcitabine.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 9","pages":"654-654"},"PeriodicalIF":66.8,"publicationDate":"2025-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144792288","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 : 2025-08-04DOI: 10.1038/s41568-025-00840-9
Jiayu Ye, Anupama Melam, Sheila A. Stewart
Ageing is a process characterized by a wide array of cellular and systemic changes that together increase the risk of developing cancer. While cell-autonomous mutations within incipient tumour cells are important, age-related changes in the microenvironment are critical partners in the transformation process and response to therapy. However, aspects of ageing that are important and the degree to which they contribute to cancer remain obscure. One of the factors that impacts ageing is increased cellular senescence but it is important to note that ageing and cellular senescence are not synonymous. We highlight open questions, including if senescent cells have phenotypically distinct impacts in aged versus young tissue, or if it is the cell type that dictates the impact of senescence on tissue homeostasis and disease. Finally, it is probable that our current definition of cellular senescence encompasses more than one mechanistically distinct cellular state; thus, we highlight phenotypic differences that have been noted across cell types and tissues of origin. This Review focuses on the role that senescent stromal cells have in cancer, with a particular emphasis on fibroblasts given the amount of work that has focused on them. Ageing influences cancer risk through cellular and environmental changes, including the induction of cellular senescence. In this Review, Ye, Melam and Stewart highlight the role of senescent stromal cells in cancer and the therapeutic implications of this.
{"title":"Stromal senescence contributes to age-related increases in cancer","authors":"Jiayu Ye, Anupama Melam, Sheila A. Stewart","doi":"10.1038/s41568-025-00840-9","DOIUrl":"10.1038/s41568-025-00840-9","url":null,"abstract":"Ageing is a process characterized by a wide array of cellular and systemic changes that together increase the risk of developing cancer. While cell-autonomous mutations within incipient tumour cells are important, age-related changes in the microenvironment are critical partners in the transformation process and response to therapy. However, aspects of ageing that are important and the degree to which they contribute to cancer remain obscure. One of the factors that impacts ageing is increased cellular senescence but it is important to note that ageing and cellular senescence are not synonymous. We highlight open questions, including if senescent cells have phenotypically distinct impacts in aged versus young tissue, or if it is the cell type that dictates the impact of senescence on tissue homeostasis and disease. Finally, it is probable that our current definition of cellular senescence encompasses more than one mechanistically distinct cellular state; thus, we highlight phenotypic differences that have been noted across cell types and tissues of origin. This Review focuses on the role that senescent stromal cells have in cancer, with a particular emphasis on fibroblasts given the amount of work that has focused on them. Ageing influences cancer risk through cellular and environmental changes, including the induction of cellular senescence. In this Review, Ye, Melam and Stewart highlight the role of senescent stromal cells in cancer and the therapeutic implications of this.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 10","pages":"781-800"},"PeriodicalIF":66.8,"publicationDate":"2025-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144777931","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 : 2025-08-01DOI: 10.1038/s41568-025-00847-2
Victoria F. Gomerdinger, Namita Nabar, Paula T. Hammond
Engineered nanoparticles have greatly expanded cancer treatment by encapsulating and delivering therapeutic and diagnostic agents, otherwise limited by poor pharmacokinetics and toxicity, to target tumour cells. Leveraging our increased understanding of the tumour microenvironment, nanomedicine has expanded to additionally target key tissues and cells implicated in tumorigenesis, such as immune and stromal cells, to improve potency and further mitigate off-target toxicities. To design nanocarriers that overcome the body’s physiological barriers to access tumours, the field has explored broader routes of administration and nanoparticle design principles, beyond the enhanced permeation and retention effect. This Review explores the advantages of non-covalent surface modifications of nanoparticles, along with other surface modifications, to modulate nanoparticle trafficking from the injection site, into tumour and lymphoid tissues, to the target cell, and ultimately its subcellular fate. Using electrostatic or other non-covalent techniques, nanoparticle surfaces can be decorated with native and synthetic macromolecules that confer highly precise cell and tissue trafficking. Rational design can additionally minimize detection and clearance by the immune system and prolong half-life — key to maximizing efficacy of therapeutic cargos. Finally, we outline how cancer nanomedicine continues to evolve by incorporating learnings from novel screening technologies, computational approaches and patient-level data to design efficacious targeted therapies. Nanoparticle surfaces can be engineered for targeted delivery of cancer therapies. In this Review, Gomerdinger, Nabar and Hammond outline the role of surface chemistry at all levels of nanoparticle trafficking, from administration route, to tissue accumulation, cellular targeting and ultimately subcellular localization. They emphasize the utility of non-covalent surface modifications for improving stealth and targeting abilities of nanoparticles for cancer.
{"title":"Advancing engineering design strategies for targeted cancer nanomedicine","authors":"Victoria F. Gomerdinger, Namita Nabar, Paula T. Hammond","doi":"10.1038/s41568-025-00847-2","DOIUrl":"10.1038/s41568-025-00847-2","url":null,"abstract":"Engineered nanoparticles have greatly expanded cancer treatment by encapsulating and delivering therapeutic and diagnostic agents, otherwise limited by poor pharmacokinetics and toxicity, to target tumour cells. Leveraging our increased understanding of the tumour microenvironment, nanomedicine has expanded to additionally target key tissues and cells implicated in tumorigenesis, such as immune and stromal cells, to improve potency and further mitigate off-target toxicities. To design nanocarriers that overcome the body’s physiological barriers to access tumours, the field has explored broader routes of administration and nanoparticle design principles, beyond the enhanced permeation and retention effect. This Review explores the advantages of non-covalent surface modifications of nanoparticles, along with other surface modifications, to modulate nanoparticle trafficking from the injection site, into tumour and lymphoid tissues, to the target cell, and ultimately its subcellular fate. Using electrostatic or other non-covalent techniques, nanoparticle surfaces can be decorated with native and synthetic macromolecules that confer highly precise cell and tissue trafficking. Rational design can additionally minimize detection and clearance by the immune system and prolong half-life — key to maximizing efficacy of therapeutic cargos. Finally, we outline how cancer nanomedicine continues to evolve by incorporating learnings from novel screening technologies, computational approaches and patient-level data to design efficacious targeted therapies. Nanoparticle surfaces can be engineered for targeted delivery of cancer therapies. In this Review, Gomerdinger, Nabar and Hammond outline the role of surface chemistry at all levels of nanoparticle trafficking, from administration route, to tissue accumulation, cellular targeting and ultimately subcellular localization. They emphasize the utility of non-covalent surface modifications for improving stealth and targeting abilities of nanoparticles for cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 9","pages":"657-683"},"PeriodicalIF":66.8,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144756374","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 : 2025-07-31DOI: 10.1038/s41568-025-00860-5
Gabrielle Brewer
In a study published in Cell, Phelps et al. find a mechanism connecting exercise, gut microbiota and anti-tumour immunity; exercise induces microbiota to produce formate, which in turn enhances CD8+ T cell functionality.
{"title":"No strain, no formate gains","authors":"Gabrielle Brewer","doi":"10.1038/s41568-025-00860-5","DOIUrl":"10.1038/s41568-025-00860-5","url":null,"abstract":"In a study published in Cell, Phelps et al. find a mechanism connecting exercise, gut microbiota and anti-tumour immunity; exercise induces microbiota to produce formate, which in turn enhances CD8+ T cell functionality.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 9","pages":"655-655"},"PeriodicalIF":66.8,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144747067","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 : 2025-07-24DOI: 10.1038/s41568-025-00848-1
Pravat Kumar Parida, Srinivas Malladi
Brain metastases remain a major clinical challenge, characterized by high mortality rates and often limited therapeutic options. The cellular and molecular processes that drive brain metastases are highly intricate, underscored by dynamic metabolic adaptations that enable tumour cells to thrive in the unique microenvironment of the brain. Emerging clinical and preclinical evidence reveals that these metabolic adaptations are not uniform but vary based on the tumour’s tissue of origin, oncogenomic landscape and capacity to endure nutrient stress. Notably, proliferative and dormant metastatic cells within the brain exhibit distinct metabolic profiles, highlighting the complexity of targeting these cells. Key metabolic pathways, including glucose, fatty acid and amino acid metabolism, are co-opted not only to sustain cancer cell survival and growth but also to modulate interactions with resident brain cells, reshaping their function to support metastasis. Importantly, this metabolic heterogeneity underscores the inadequacy of a one-size-fits-all therapeutic approach. Here, we review the adaptive metabolic reprogramming that facilitates brain metastases and discuss emerging strategies to tailor interventions aimed at preventing and treating overt brain metastases. In this Review, Parida and Malladi summarize the metabolic adaptations of tumour cells upon dissemination to the brain, outline the metabolic crosstalk between cancer and brain-resident cells and discuss potential strategies to target these adaptations to improve outcomes for patients with brain metastasis.
{"title":"Metabolic adaptations of brain metastasis","authors":"Pravat Kumar Parida, Srinivas Malladi","doi":"10.1038/s41568-025-00848-1","DOIUrl":"10.1038/s41568-025-00848-1","url":null,"abstract":"Brain metastases remain a major clinical challenge, characterized by high mortality rates and often limited therapeutic options. The cellular and molecular processes that drive brain metastases are highly intricate, underscored by dynamic metabolic adaptations that enable tumour cells to thrive in the unique microenvironment of the brain. Emerging clinical and preclinical evidence reveals that these metabolic adaptations are not uniform but vary based on the tumour’s tissue of origin, oncogenomic landscape and capacity to endure nutrient stress. Notably, proliferative and dormant metastatic cells within the brain exhibit distinct metabolic profiles, highlighting the complexity of targeting these cells. Key metabolic pathways, including glucose, fatty acid and amino acid metabolism, are co-opted not only to sustain cancer cell survival and growth but also to modulate interactions with resident brain cells, reshaping their function to support metastasis. Importantly, this metabolic heterogeneity underscores the inadequacy of a one-size-fits-all therapeutic approach. Here, we review the adaptive metabolic reprogramming that facilitates brain metastases and discuss emerging strategies to tailor interventions aimed at preventing and treating overt brain metastases. In this Review, Parida and Malladi summarize the metabolic adaptations of tumour cells upon dissemination to the brain, outline the metabolic crosstalk between cancer and brain-resident cells and discuss potential strategies to target these adaptations to improve outcomes for patients with brain metastasis.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 9","pages":"723-739"},"PeriodicalIF":66.8,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144693973","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 : 2025-07-23DOI: 10.1038/s41568-025-00856-1
Promeet Halder, Mrinal Srivastava
In this Journal Club, Halder and Srivastava discuss a study that investigated how activation-induced deaminase (AID)-mediated DNA double-strand breaks lead to translocations in a cell type-specific manner.
{"title":"Replication timings affect the frequency of chromosomal translocation","authors":"Promeet Halder, Mrinal Srivastava","doi":"10.1038/s41568-025-00856-1","DOIUrl":"10.1038/s41568-025-00856-1","url":null,"abstract":"In this Journal Club, Halder and Srivastava discuss a study that investigated how activation-induced deaminase (AID)-mediated DNA double-strand breaks lead to translocations in a cell type-specific manner.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 12","pages":"886-886"},"PeriodicalIF":66.8,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144684657","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 : 2025-07-22DOI: 10.1038/s41568-025-00854-3
Meadow Parrish, Charlotte Kuperwasser
Rising rates of early-onset oestrogen receptor-positive (ER+) breast cancer in women without genetic risk suggest a shift in disease biology. Chronic and cumulative exposure to endocrine-disrupting chemicals may induce field cancerization in the breast, warranting urgent attention from researchers, regulators and public health leaders. Rising rates of early-onset oestrogen receptor-positive (ER+) breast cancer in women without genetic risk suggest a shift in disease biology. Endocrine-disrupting chemicals (EDCs) may accelerate tissue ageing, destabilize epigenetic regulation and impair immune surveillance. Chronic and cumulative EDC exposure may induce field cancerization in the breast, warranting urgent attention from researchers, regulators and public health leaders.
{"title":"Environmental endocrine disruptors: rethinking the origins of early-onset ER+ breast cancer","authors":"Meadow Parrish, Charlotte Kuperwasser","doi":"10.1038/s41568-025-00854-3","DOIUrl":"10.1038/s41568-025-00854-3","url":null,"abstract":"Rising rates of early-onset oestrogen receptor-positive (ER+) breast cancer in women without genetic risk suggest a shift in disease biology. Chronic and cumulative exposure to endocrine-disrupting chemicals may induce field cancerization in the breast, warranting urgent attention from researchers, regulators and public health leaders. Rising rates of early-onset oestrogen receptor-positive (ER+) breast cancer in women without genetic risk suggest a shift in disease biology. Endocrine-disrupting chemicals (EDCs) may accelerate tissue ageing, destabilize epigenetic regulation and impair immune surveillance. Chronic and cumulative EDC exposure may induce field cancerization in the breast, warranting urgent attention from researchers, regulators and public health leaders.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 11","pages":"819-820"},"PeriodicalIF":66.8,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677441","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 : 2025-07-18DOI: 10.1038/s41568-025-00859-y
Jess D. Hebert
In this Tools of the Trade article, Jess Hebert describes the development and use of Cas12a mice for the unbiased, high-throughput generation and interrogation of complex tumour genotypes.
{"title":"Cas12a mice enable the rapid generation of highly complex tumour genotypes","authors":"Jess D. Hebert","doi":"10.1038/s41568-025-00859-y","DOIUrl":"10.1038/s41568-025-00859-y","url":null,"abstract":"In this Tools of the Trade article, Jess Hebert describes the development and use of Cas12a mice for the unbiased, high-throughput generation and interrogation of complex tumour genotypes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 12","pages":"885-885"},"PeriodicalIF":66.8,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652275","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 : 2025-07-17DOI: 10.1038/s41568-025-00855-2
Jingxuan Zhao, Cathy J. Bradley, Ya-Chen Tina Shih, K. Robin Yabroff
People in the USA who are incarcerated, or have a history of incarceration, face worse access to cancer care, leading to poorer outcomes. Addressing these inequities requires coordinated action across research, healthcare, policy and correctional systems to ensure all individuals — regardless of incarceration history — have access to high-quality cancer care. People in the USA who are incarcerated, or have a history of incarceration, face worse access to cancer care, leading to poorer outcomes. In this Comment, Zhao and colleagues highlight the need to address these inequities through coordinated action across research, healthcare, policy and correctional systems to ensure all individuals have access to high-quality cancer care.
{"title":"Incarceration and cancer care disparities in the USA","authors":"Jingxuan Zhao, Cathy J. Bradley, Ya-Chen Tina Shih, K. Robin Yabroff","doi":"10.1038/s41568-025-00855-2","DOIUrl":"10.1038/s41568-025-00855-2","url":null,"abstract":"People in the USA who are incarcerated, or have a history of incarceration, face worse access to cancer care, leading to poorer outcomes. Addressing these inequities requires coordinated action across research, healthcare, policy and correctional systems to ensure all individuals — regardless of incarceration history — have access to high-quality cancer care. People in the USA who are incarcerated, or have a history of incarceration, face worse access to cancer care, leading to poorer outcomes. In this Comment, Zhao and colleagues highlight the need to address these inequities through coordinated action across research, healthcare, policy and correctional systems to ensure all individuals have access to high-quality cancer care.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 12","pages":"881-882"},"PeriodicalIF":66.8,"publicationDate":"2025-07-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144652520","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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