{"title":"Developing multiple EGFR-mutant lung cancers","authors":"Daniela Senft","doi":"10.1038/s41568-024-00773-9","DOIUrl":"10.1038/s41568-024-00773-9","url":null,"abstract":"The occurrence of multiple independent tumours in patients with EGFR-mutant lung cancer was unexplained. A recent study in Nature Cancer identified distinct genetic predisposition mechanisms, including developmental mosaicism and germline EGFR variants, that contribute to the formation of multiple primary tumours.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"826-826"},"PeriodicalIF":72.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142588706","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":"Fanconi anaemia pathway induces chromosome shattering","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00774-8","DOIUrl":"10.1038/s41568-024-00774-8","url":null,"abstract":"Engel et al. conducted a genetic screen in which they identified the Fanconi anaemia (FA) pathway as a driver of chromothripsis, complex genomic rearrangements and generation of extrachromosomal DNA.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"827-827"},"PeriodicalIF":72.5,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142589120","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":"Author Correction: The importance of 3D fibre architecture in cancer and implications for biomaterial model design","authors":"Jennifer C. Ashworth, Thomas R. Cox","doi":"10.1038/s41568-024-00776-6","DOIUrl":"https://doi.org/10.1038/s41568-024-00776-6","url":null,"abstract":"<p>Correction to: <i>Nature Reviews Cancer</i> https://doi.org/10.1038/s41568-024-00704-8, published online 17 June 2024.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"241 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574371","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":"Characterization of the B cell receptor repertoire in melanoma","authors":"Jisu Chae, Junho Chung","doi":"10.1038/s41568-024-00770-y","DOIUrl":"https://doi.org/10.1038/s41568-024-00770-y","url":null,"abstract":"In this Journal Club, Chae and Chung discuss a study characterizing the differentiation and maturation of both tumour-resident and circulating B cells in patients with melanoma.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"142 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142574373","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":"Midkine crisis fuels age-related tumorigenesis","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00771-x","DOIUrl":"10.1038/s41568-024-00771-x","url":null,"abstract":"Ageing is a well-accepted risk factor for developing cancer. Yan et al. used a preclinical rat model to study the mechanisms facilitating the age-associated increase in breast tumorigenesis.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"828-828"},"PeriodicalIF":72.5,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142555943","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}
Rand Arafeh, Tsukasa Shibue, Joshua M. Dempster, William C. Hahn, Francisca Vazquez
{"title":"The present and future of the Cancer Dependency Map","authors":"Rand Arafeh, Tsukasa Shibue, Joshua M. Dempster, William C. Hahn, Francisca Vazquez","doi":"10.1038/s41568-024-00763-x","DOIUrl":"https://doi.org/10.1038/s41568-024-00763-x","url":null,"abstract":"<p>Despite tremendous progress in the past decade, the complex and heterogeneous nature of cancer complicates efforts to identify new therapies and therapeutic combinations that achieve durable responses in most patients. Further advances in cancer therapy will rely, in part, on the development of targeted therapeutics matched with the genetic and molecular characteristics of cancer. The Cancer Dependency Map (DepMap) is a large-scale data repository and research platform, aiming to systematically reveal the landscape of cancer vulnerabilities in thousands of genetically and molecularly annotated cancer models. DepMap is used routinely by cancer researchers and translational scientists and has facilitated the identification of several novel and selective therapeutic strategies for multiple cancer types that are being tested in the clinic. However, it is also clear that the current version of DepMap is not yet comprehensive. In this Perspective, we review (1) the impact and current uses of DepMap, (2) the opportunities to enhance DepMap to overcome its current limitations, and (3) the ongoing efforts to further improve and expand DepMap.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"96 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142519250","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":"Stemness in solid malignancies: coping with immune attack","authors":"Judith Agudo, Yuxuan Miao","doi":"10.1038/s41568-024-00760-0","DOIUrl":"https://doi.org/10.1038/s41568-024-00760-0","url":null,"abstract":"<p>Immunotherapy has become a key new pillar of cancer treatment, and this has sparked interest in understanding mechanisms of cancer immune evasion. It has long been appreciated that cancers are constituted by heterogeneous populations of tumour cells. This feature is often fuelled by specialized cells that have molecular programs resembling tissue stem cells. Although these cancer stem cells (CSCs) have capacity for unlimited self-renewal and differentiation, it is increasingly evident that some CSCs are capable of achieving remarkable immune resistance. Given that most immunotherapy regiments have overlooked CSC-specific immune-evasive mechanisms, many current treatment strategies often lead to cancer relapse. This Review focuses on advancements in understanding how CSCs in solid tumours achieve their unique immune-evasive properties, enabling them to drive tumour regrowth. Moreover, as cancers often arise from tissue stem cells that acquired oncogenic mutations, we discuss how tissue stem cells undergoing malignant transformation activate intrinsic immune-evasive mechanisms and establish close interactions with suppressive immune cells to escape immune surveillance. In addition, we summarize how in advanced disease stages, CSCs often hijack features of normal stem cells to resist antitumour immunity. Finally, we provide insights in how to design a new generation of cancer immunotherapies to ensure elimination of CSCs.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"15 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489808","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}
Douglas Hanahan, Olivier Michielin, Mikael J. Pittet
{"title":"Convergent inducers and effectors of T cell paralysis in the tumour microenvironment","authors":"Douglas Hanahan, Olivier Michielin, Mikael J. Pittet","doi":"10.1038/s41568-024-00761-z","DOIUrl":"https://doi.org/10.1038/s41568-024-00761-z","url":null,"abstract":"<p>Tumorigenesis embodies the formation of a heterotypic tumour microenvironment (TME) that, among its many functions, enables the evasion of T cell-mediated immune responses. Remarkably, most TME cell types, including cancer cells, fibroblasts, myeloid cells, vascular endothelial cells and pericytes, can be stimulated to deploy immunoregulatory programmes. These programmes involve regulatory inducers (signals-in) and functional effectors (signals-out) that impair CD8<sup>+</sup> and CD4<sup>+</sup> T cell activity through cytokines, growth factors, immune checkpoints and metabolites. Some signals target specific cell types, whereas others, such as transforming growth factor-β (TGFβ) and prostaglandin E<sub>2</sub> (PGE<sub>2</sub>), exert broad, pleiotropic effects; as signals-in, they trigger immunosuppressive programmes in most TME cell types, and as signals-out, they directly inhibit T cells and also modulate other cells to reinforce immunosuppression. This functional diversity and redundancy pose a challenge for therapeutic targeting of the immune-evasive TME. Fundamentally, the commonality of regulatory programmes aimed at abrogating T cell activity, along with paracrine signalling between cells of the TME, suggests that many normal cell types are hard-wired with latent functions that can be triggered to prevent inappropriate immune attack. This intrinsic capability is evidently co-opted throughout the TME, enabling tumours to evade immune destruction.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"63 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488367","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":"High-resolution measurement of individual telomere lengths with Telo-seq","authors":"Carly Tyer","doi":"10.1038/s41568-024-00767-7","DOIUrl":"https://doi.org/10.1038/s41568-024-00767-7","url":null,"abstract":"In this Tools of the Trade article, Carly Tyer describes the development of Telo-seq, a method to enrich and sequence all telomeres within a sample, and highlights its use in distinguishing between the two telomere maintenance mechanisms used in cancer cells.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"29 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142486633","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":"Emerging strategies to investigate the biology of early cancer","authors":"Ran Zhou, Xiwen Tang, Yuan Wang","doi":"10.1038/s41568-024-00754-y","DOIUrl":"10.1038/s41568-024-00754-y","url":null,"abstract":"Early detection and intervention of cancer or precancerous lesions hold great promise to improve patient survival. However, the processes of cancer initiation and the normal–precancer–cancer progression within a non-cancerous tissue context remain poorly understood. This is, in part, due to the scarcity of early-stage clinical samples or suitable models to study early cancer. In this Review, we introduce clinical samples and model systems, such as autochthonous mice and organoid-derived or stem cell-derived models that allow longitudinal analysis of early cancer development. We also present the emerging techniques and computational tools that enhance our understanding of cancer initiation and early progression, including direct imaging, lineage tracing, single-cell and spatial multi-omics, and artificial intelligence models. Together, these models and techniques facilitate a more comprehensive understanding of the poorly characterized early malignant transformation cascade, holding great potential to unveil key drivers and early biomarkers for cancer development. Finally, we discuss how these new insights can potentially be translated into mechanism-based strategies for early cancer detection and prevention. Understanding the early steps of cancer development is crucial for cancer prevention. In this Review, the authors summarize the advantages and limitations of clinical samples, autochthonous mouse models and organoid models, alongside advanced techniques such as direct imaging, lineage tracing and AI, to enhance understanding of early cancer progression.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 12","pages":"850-866"},"PeriodicalIF":72.5,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142452535","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}