Nature Reviews Cancer最新文献

{"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":"10.1038/s41568-025-00791-1","url":null,"abstract":"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. While progress has been made in treating advanced non-small-cell lung cancer, patients would further benefit from methods that detect progressive premalignant lesions and strategies that effectively intercept progression. In this Review, Mazzilli et al. explore recent advances in identifying premalignant lesions, highlighting their disease aetiology and devising approaches for stratification and interventions aimed at halting the progression to cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 5","pages":"379-392"},"PeriodicalIF":66.8,"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, Michael J. Overman, Konstantinos I. Votanopoulos, Andrew M. Lowy, Patrick Wagner, Mary K. Washington, Cathy Eng, Wai Chin Foo, Richard M. Goldberg, Mojgan Hosseini, Kamran Idrees, Douglas B. Johnson, Ardaman Shergill, Erin Ward, Nicholas C. Zachos, Deborah Shelton, 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}

{"title":"Using mathematical modelling and AI to improve delivery and efficacy of therapies in cancer","authors":"Constantinos Harkos, Andreas G. Hadjigeorgiou, Chrysovalantis Voutouri, Ashwin S. Kumar, Triantafyllos Stylianopoulos, Rakesh K. Jain","doi":"10.1038/s41568-025-00796-w","DOIUrl":"10.1038/s41568-025-00796-w","url":null,"abstract":"Mathematical modelling has proven to be a valuable tool in predicting the delivery and efficacy of molecular, antibody-based, nano and cellular therapy in solid tumours. Mathematical models based on our understanding of the biological processes at subcellular, cellular and tissue level are known as mechanistic models that, in turn, are divided into continuous and discrete models. Continuous models are further divided into lumped parameter models — for describing the temporal distribution of medicine in tumours and normal organs — and distributed parameter models — for studying the spatiotemporal distribution of therapy in tumours. Discrete models capture interactions at the cellular and subcellular levels. Collectively, these models are useful for optimizing the delivery and efficacy of molecular, nanoscale and cellular therapy in tumours by incorporating the biological characteristics of tumours, the physicochemical properties of drugs, the interactions among drugs, cancer cells and various components of the tumour microenvironment, and for enabling patient-specific predictions when combined with medical imaging. Artificial intelligence-based methods, such as machine learning, have ushered in a new era in oncology. These data-driven approaches complement mechanistic models and have immense potential for improving cancer detection, treatment and drug discovery. Here we review these diverse approaches and suggest ways to combine mechanistic and artificial intelligence-based models to further improve patient treatment outcomes. Here Harkos et al. review the role of continuous models and discrete models in predicting and understanding therapy delivery and efficacy in solid tumours. They propose ways to integrate mechanistic and AI-based models to further improve patient outcomes.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 5","pages":"324-340"},"PeriodicalIF":66.8,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143443439","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":"Dendritic cell maturation in cancer","authors":"Chang Yoon Moon, Meriem Belabed, Matthew D. Park, Raphaël Mattiuz, Daniel Puleston, Miriam Merad","doi":"10.1038/s41568-024-00787-3","DOIUrl":"10.1038/s41568-024-00787-3","url":null,"abstract":"Dendritic cells (DCs) are specialized antigen-presenting cells that are present at low abundance in the circulation and tissues; they serve as crucial immune sentinels by continually sampling their environment, migrating to secondary lymphoid organs and shaping adaptive immune responses through antigen presentation. Owing to their ability to orchestrate tolerogenic or immunogenic responses to a specific antigen, DCs have a pivotal role in antitumour immunity and the response to immune checkpoint blockade and other immunotherapeutic approaches. The multifaceted functions of DCs are acquired through a complex, multistage process called maturation. Although the role of inflammatory triggers in driving DC maturation was established decades ago, less is known about DC maturation in non-inflammatory contexts, such as during homeostasis and in cancer. The advent of single-cell technologies has enabled an unbiased, high-dimensional characterization of various DC states, including mature DCs. This approach has clarified the molecular programmes associated with DC maturation and also revealed how cancers exploit these pathways to subvert immune surveillance. In this Review, we discuss the mechanisms by which cancer disrupts DC maturation and highlight emerging therapeutic opportunities to modulate DC states. These insights could inform the development of DC-centric immunotherapies, expanding the arsenal of strategies to enhance antitumour immunity. Dendritic cells (DCs) shape the adaptive immune response to peripheral tissue antigens and, as such, are crucial for mounting an effective antitumour immune response in cancer. This Review outlines the molecular basis of DC maturation, highlights the mechanisms through which cancer impairs DC maturation and considers the potential for DC-focused cancer immunotherapeutics.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 4","pages":"225-248"},"PeriodicalIF":72.5,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143367372","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":"Small speckles, big impact","authors":"Daniela Senft","doi":"10.1038/s41568-025-00794-y","DOIUrl":"10.1038/s41568-025-00794-y","url":null,"abstract":"In this study, Alexander et al. find that HIF2α regulates speckle–DNA associations to fine-tune the expression of a subset of its target genes, and demonstrate that speckle phenotypes correlate with outcomes in renal cell carcinoma.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"149-149"},"PeriodicalIF":72.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143071848","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":"Maximizing the dual benefit of pet dogs in cancer trials","authors":"Jennifer A. Lenz, Matthew J. Atherton","doi":"10.1038/s41568-025-00792-0","DOIUrl":"10.1038/s41568-025-00792-0","url":null,"abstract":"Pet dogs with cancer have catalysed the translation of preclinical discoveries to first-in-human trials, highlighting the unique power of comparative oncology to study veterinary and human patients with cancer in parallel. However, the full potential of this approach has yet to be harnessed. Here we highlight accomplishments in oncology due to trials in dogs and discuss the next steps to advance comparative oncology. Pet dogs with cancer facilitate comparative oncology, enhancing translational research. In this Comment, Lenz and Atherton highlight comparative oncology successes, emphasizing the need for broader application of findings from canine studies to improve human cancer treatments.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"147-148"},"PeriodicalIF":72.5,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143072482","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":"Allies in the epidermis","authors":"Gabrielle Brewer","doi":"10.1038/s41568-025-00793-z","DOIUrl":"10.1038/s41568-025-00793-z","url":null,"abstract":"Immunosuppression disrupts normal skin homeostasis, raising the risk of cancer development. Now, Son et al. find that commensal papillomavirus maintains homeostasis in sun-damaged skin.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"25 3","pages":"150-150"},"PeriodicalIF":72.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056475","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":"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}

{"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}

{"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}