Nature Reviews Cancer最新文献_第6页

Small speckles, big impact 小斑点，大影响

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-31 DOI: 10.1038/s41568-025-00794-y

Daniela Senft

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Maximizing the dual benefit of pet dogs in cancer trials 使宠物狗在癌症试验中的双重益处最大化

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-31 DOI: 10.1038/s41568-025-00792-0

Jennifer A. Lenz, Matthew J. Atherton

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Allies in the epidermis 在表皮上的同盟军

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-30 DOI: 10.1038/s41568-025-00793-z

Gabrielle Brewer

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Cross-priming in cancer immunology and immunotherapy 癌症免疫学和免疫治疗中的交叉启动

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-29 DOI: 10.1038/s41568-024-00785-5

Carlos Luri-Rey, Álvaro Teijeira, Stefanie K. Wculek, Carlos de Andrea, Claudia Herrero, Alvaro Lopez-Janeiro, María E. Rodríguez-Ruiz, Ignacio Heras, Maria Aggelakopoulou, Pedro Berraondo, David Sancho, Ignacio Melero

{"title":"Cross-priming in cancer immunology and immunotherapy","authors":"Carlos Luri-Rey, Álvaro Teijeira, Stefanie K. Wculek, Carlos de Andrea, Claudia Herrero, Alvaro Lopez-Janeiro, María E. Rodríguez-Ruiz, Ignacio Heras, Maria Aggelakopoulou, Pedro Berraondo, David Sancho, Ignacio Melero","doi":"10.1038/s41568-024-00785-5","DOIUrl":"10.1038/s41568-024-00785-5","url":null,"abstract":"Cytotoxic T cell immune responses against cancer crucially depend on the ability of a subtype of professional antigen-presenting cells termed conventional type 1 dendritic cells (cDC1s) to cross-present antigens. Cross-presentation comprises redirection of exogenous antigens taken from other cells to the major histocompatibility complex class I antigen-presenting machinery. In addition, once activated and having sensed viral moieties or T helper cell cooperation via CD40–CD40L interactions, cDC1s provide key co-stimulatory ligands and cytokines to mount and sustain CD8+ T cell immune responses. This regulated process of cognate T cell activation is termed cross-priming. In cancer mouse models, CD8+ T cell cross-priming by cDC1s is crucial for the efficacy of most, if not all, immunotherapy strategies. In patients with cancer, the presence and abundance of cDC1s in the tumour microenvironment is markedly associated with the level of T cell infiltration and responsiveness to immune checkpoint inhibitors. Therapeutic strategies to increase the numbers of cDC1s using FMS-like tyrosine kinase 3 ligand (FLT3L) and/or their activation status show evidence of efficacy in cancer mouse models and are currently being tested in initial clinical trials with promising results so far. In this Review, Luri-Rey et al. present evidence for the crucial role of conventional type 1 dendritic cells in cross-presenting antigens from other cells via the major histocompatibility complex class I antigen-presenting machinery, which in turn is necessary to prime CD8+ T cells, which then mount efficient immune responses against cancer. The authors also discuss how we can exploit these processes in cancer immunotherapy by increasing the number and/or maturation or activation status of this specialist subtype of antigen-presenting cell.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"249-273"},"PeriodicalIF":72.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054935","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}

引用次数: 0

Tumour hypoxia in driving genomic instability and tumour evolution 肿瘤缺氧驱动基因组不稳定性和肿瘤进化

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-28 DOI: 10.1038/s41568-024-00781-9

Alexandru Suvac, Jack Ashton, Robert G. Bristow

{"title":"Tumour hypoxia in driving genomic instability and tumour evolution","authors":"Alexandru Suvac, Jack Ashton, Robert G. Bristow","doi":"10.1038/s41568-024-00781-9","DOIUrl":"10.1038/s41568-024-00781-9","url":null,"abstract":"Intratumour hypoxia is a feature of all heterogenous solid tumours. Increased levels or subregions of tumour hypoxia are associated with an adverse clinical prognosis, particularly when this co-occurs with genomic instability. Experimental evidence points to the acquisition of DNA and chromosomal alterations in proliferating hypoxic cells secondary to inhibition of DNA repair pathways such as homologous recombination, base excision repair and mismatch repair. Cell adaptation and selection in repair-deficient cells give rise to a model whereby novel single-nucleotide mutations, structural variants and copy number alterations coexist with altered mitotic control to drive chromosomal instability and aneuploidy. Whole-genome sequencing studies support the concept that hypoxia is a critical microenvironmental cofactor alongside the driver mutations in MYC, BCL2, TP53 and PTEN in determining clonal and subclonal evolution in multiple tumour types. We propose that the hypoxic tumour microenvironment selects for unstable tumour clones which survive, propagate and metastasize under reduced immune surveillance. These aggressive features of hypoxic tumour cells underpin resistance to local and systemic therapies and unfavourable outcomes for patients with cancer. Possible ways to counter the effects of hypoxia to block tumour evolution and improve treatment outcomes are described. In this Review, Suvac et al. discuss how intratumoural hypoxia is a driving force in tumour evolution, alongside driver gene mutations, through the generation of genomic instability. The resultant selected unstable tumour clones underpin resistance to local and systemic therapies and unfavourable outcomes for patients with cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"167-188"},"PeriodicalIF":72.5,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054987","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}

引用次数: 0

Metabolic interplays between the tumour and the host shape the tumour macroenvironment 肿瘤和宿主之间的代谢相互作用塑造了肿瘤的宏观环境

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-20 DOI: 10.1038/s41568-024-00786-4

Patricia Altea-Manzano, Amanda Decker-Farrell, Tobias Janowitz, Ayelet Erez

{"title":"Metabolic interplays between the tumour and the host shape the tumour macroenvironment","authors":"Patricia Altea-Manzano, Amanda Decker-Farrell, Tobias Janowitz, Ayelet Erez","doi":"10.1038/s41568-024-00786-4","DOIUrl":"10.1038/s41568-024-00786-4","url":null,"abstract":"Metabolic reprogramming of cancer cells and the tumour microenvironment are pivotal characteristics of cancers, and studying these processes offer insights and avenues for cancer diagnostics and therapeutics. Recent advancements have underscored the impact of host systemic features, termed macroenvironment, on facilitating cancer progression. During tumorigenesis, these inherent features of the host, such as germline genetics, immune profile and the metabolic status, influence how the body responds to cancer. In parallel, as cancer grows, it induces systemic effects beyond the primary tumour site and affects the macroenvironment, for example, through inflammation, the metabolic end-stage syndrome of cachexia, and metabolic dysregulation. Therefore, understanding the intricate metabolic interplay between the tumour and the host is a growing frontier in advancing cancer diagnosis and therapy. In this Review, we explore the specific contribution of the metabolic fitness of the host to cancer initiation, progression and response to therapy. We then delineate the complex metabolic crosstalk between the tumour, the microenvironment and the host, which promotes disease progression to metastasis and cachexia. The metabolic relationships among the host, cancer pathogenesis and the consequent responsive systemic manifestations during cancer progression provide new perspectives for mechanistic cancer therapy and improved management of patients with cancer. In this Review, Erez and colleagues examine the complex interactions among tumours, their microenvironment and the host, shaping a metabolic macroenvironment that drives cancer progression. They explore how this crosstalk impacts on metastasis, inflammation and cachexia, providing insights for enhanced cancer management.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"274-292"},"PeriodicalIF":72.5,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142989854","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}

引用次数: 0

Rusting away with age 因岁月而生锈的

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-14 DOI: 10.1038/s41568-025-00790-2

Gabrielle Brewer

引用次数: 0

Decoding the functional impact of the cancer genome through protein–protein interactions 通过蛋白质与蛋白质之间的相互作用解码癌症基因组的功能影响

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-14 DOI: 10.1038/s41568-024-00784-6

Haian Fu, Xiulei Mo, Andrey A. Ivanov

{"title":"Decoding the functional impact of the cancer genome through protein–protein interactions","authors":"Haian Fu, Xiulei Mo, Andrey A. Ivanov","doi":"10.1038/s41568-024-00784-6","DOIUrl":"10.1038/s41568-024-00784-6","url":null,"abstract":"Acquisition of genomic mutations enables cancer cells to gain fitness advantages under selective pressure and, ultimately, leads to oncogenic transformation. Interestingly, driver mutations, even within the same gene, can yield distinct phenotypes and clinical outcomes, necessitating a mutation-focused approach. Conversely, cellular functions are governed by molecular machines and signalling networks that are mostly controlled by protein–protein interactions (PPIs). The functional impact of individual genomic alterations could be transmitted through regulated nodes and hubs of PPIs. Oncogenic mutations may lead to modified residues of proteins, enabling interactions with other proteins that the wild-type protein does not typically interact with, or preventing interactions with proteins that the wild-type protein usually interacts with. This can result in the rewiring of molecular signalling cascades and the acquisition of an oncogenic phenotype. Here, we review the altered PPIs driven by oncogenic mutations, discuss technologies for monitoring PPIs and provide a functional analysis of mutation-directed PPIs. These driver mutation-enabled PPIs and mutation-perturbed PPIs present a new paradigm for the development of tumour-specific therapeutics. The intersection of cancer variants and altered PPI interfaces represents a new frontier for understanding oncogenic rewiring and developing tumour-selective therapeutic strategies. Genomic mutations can be translated into modified functional proteins, impacting protein–protein interactions (PPIs) and thus altering cellular functions. In this Review, Fu, Mo and Ivanov summarize the mechanisms by which oncogenic mutations impact PPIs, technologies for monitoring this, the categories and features of PPIs in cancer, and finally the therapeutic implications of this.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"189-208"},"PeriodicalIF":72.5,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142974771","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}

引用次数: 0

Fructose takes a detour to feed cancer 果糖绕道而行，滋养癌症

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2025-01-08 DOI: 10.1038/s41568-024-00789-1

Daniela Senft

引用次数: 0

PDX models for functional precision oncology and discovery science 用于功能性精准肿瘤学和发现科学的 PDX 模型

IF 72.5 1区医学

Nature Reviews Cancer Pub Date : 2024-12-16 DOI: 10.1038/s41568-024-00779-3

Zannel Blanchard, Elisabeth A. Brown, Arevik Ghazaryan, Alana L. Welm

{"title":"PDX models for functional precision oncology and discovery science","authors":"Zannel Blanchard, Elisabeth A. Brown, Arevik Ghazaryan, Alana L. Welm","doi":"10.1038/s41568-024-00779-3","DOIUrl":"10.1038/s41568-024-00779-3","url":null,"abstract":"Precision oncology relies on detailed molecular analysis of how diverse tumours respond to various therapies, with the aim to optimize treatment outcomes for individual patients. Patient-derived xenograft (PDX) models have been key to preclinical validation of precision oncology approaches, enabling the analysis of each tumour’s unique genomic landscape and testing therapies that are predicted to be effective based on specific mutations, gene expression patterns or signalling abnormalities. To extend these standard precision oncology approaches, the field has strived to complement the otherwise static and often descriptive measurements with functional assays, termed functional precision oncology (FPO). By utilizing diverse PDX and PDX-derived models, FPO has gained traction as an effective preclinical and clinical tool to more precisely recapitulate patient biology using in vivo and ex vivo functional assays. Here, we explore advances and limitations of PDX and PDX-derived models for precision oncology and FPO. We also examine the future of PDX models for precision oncology in the age of artificial intelligence. Integrating these two disciplines could be the key to fast, accurate and cost-effective treatment prediction, revolutionizing oncology and providing patients with cancer with the most effective, personalized treatments. Patient-derived xenograft (PDX) models are valuable surrogates for drug testing in precision oncology. In this Review, Welm and colleagues outline the opportunities and challenges of PDX models, discuss their relevance in functional precision oncology for replicating patient biology and share their perspective on how integrating these models with artificial intelligence can enhance their utility for personalizing cancer treatment.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"153-166"},"PeriodicalIF":72.5,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142825466","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}

引用次数: 0