{"title":"Pre-empting drug resistance","authors":"Anna Dart","doi":"10.1038/s41568-024-00729-z","DOIUrl":"10.1038/s41568-024-00729-z","url":null,"abstract":"Leighow et al. develop a strategy called the dual-switch selection gene drive platform, which enables the evolutionary dynamics of acquired resistance to be manipulated for therapeutic ends.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 9","pages":"594-594"},"PeriodicalIF":72.5,"publicationDate":"2024-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759988","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":"The impact of sex on metastasis","authors":"Yingsheng Zhang, Xue Li","doi":"10.1038/s41568-024-00725-3","DOIUrl":"10.1038/s41568-024-00725-3","url":null,"abstract":"Sex matters in metastasis, but it has received little attention in research. Here, we highlight the emerging and important roles of biological sex in metastasis and advocate for mechanistic and quantitative studies for the future development of sex-tailored therapies.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 10","pages":"647-648"},"PeriodicalIF":72.5,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141736909","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":"In-depth organoid profiling of pancreatic cancer","authors":"Ju Eun Maeng, Ja-Lok Ku","doi":"10.1038/s41568-024-00726-2","DOIUrl":"10.1038/s41568-024-00726-2","url":null,"abstract":"In this Journal Club, Maeng and Ku discuss a study demonstrating that profiling drug responses in patient-derived organoids can identify responders to various therapies.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 9","pages":"596-596"},"PeriodicalIF":72.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561409","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}
Amir Z. Munir, Alan Gutierrez, Juan Qin, Andrew H. Lichtman, Javid J. Moslehi
{"title":"Immune-checkpoint inhibitor-mediated myocarditis: CTLA4, PD1 and LAG3 in the heart","authors":"Amir Z. Munir, Alan Gutierrez, Juan Qin, Andrew H. Lichtman, Javid J. Moslehi","doi":"10.1038/s41568-024-00715-5","DOIUrl":"10.1038/s41568-024-00715-5","url":null,"abstract":"Immune-checkpoint inhibitors (ICIs) have revolutionized oncology, with nearly 50% of all patients with cancer eligible for treatment with ICIs. However, patients on ICI therapy are at risk for immune-related toxicities that can affect any organ. Inflammation of the heart muscle, known as myocarditis, resulting from ICI targeting cytotoxic T lymphocyte-associated antigen 4 (CTLA4), programmed cell death protein 1 (PD1) and PD1 ligand 1 (PDL1) is an infrequent but potentially fatal complication. ICI-mediated myocarditis (ICI-myocarditis) is a growing clinical entity given the widespread use of ICIs, its increased clinical recognition and growing use of combination ICI treatment, a well-documented risk factor for ICI-myocarditis. In this Review, we approach ICI-myocarditis from a basic and mechanistic perspective, synthesizing the recent data from both preclinical models and patient samples. We posit that mechanistic understanding of the fundamental biology of immune-checkpoint molecules may yield new insights into disease processes, which will enable improvement in diagnostic and therapeutic approaches. The syndrome of ICI-myocarditis is novel, and our understanding of immune checkpoints in the heart is in its nascency. Yet, investigations into the pathophysiology will inform better patient risk stratification, improved diagnostics and precision-based therapies for patients. Despite the success of immune-checkpoint inhibitors, many patients are at risk of developing immune-related adverse events. One of these is myocarditis or inflammation of the heart. Munir, Gutierrez and colleagues describe the data from preclinical models and patient samples, which have begun to provide a mechanistic understanding of myocarditis resulting from immune-checkpoint inhibitors, and present suggestions for improving both the diagnosis and treatment of patients experiencing this immune-related toxicity.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 8","pages":"540-553"},"PeriodicalIF":72.5,"publicationDate":"2024-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561410","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 organoids 2.0: modelling the complexity of the tumour immune microenvironment","authors":"Roel Polak, Elisa T. Zhang, Calvin J. Kuo","doi":"10.1038/s41568-024-00706-6","DOIUrl":"10.1038/s41568-024-00706-6","url":null,"abstract":"The development of neoplasia involves a complex and continuous interplay between malignantly transformed cells and the tumour microenvironment (TME). Cancer immunotherapies targeting the immune TME have been increasingly validated in clinical trials but response rates vary substantially between tumour histologies and are often transient, idiosyncratic and confounded by resistance. Faithful experimental models of the patient-specific tumour immune microenvironment, capable of recapitulating tumour biology and immunotherapy effects, would greatly improve patient selection, target identification and definition of resistance mechanisms for immuno-oncology therapeutics. In this Review, we discuss currently available and rapidly evolving 3D tumour organoid models that capture important immune features of the TME. We highlight diverse opportunities for organoid-based investigations of tumour immunity, drug development and precision medicine. In this Review, Polak, Zhang and Kuo discuss the currently available and rapidly evolving 3D tumour organoid models that capture the tumour immune microenvironment. They highlight opportunities for organoid-based investigations of tumour immunity, drug development and precision medicine.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 8","pages":"523-539"},"PeriodicalIF":72.5,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141559302","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}
Michael A. Harris, Peter Savas, Balaji Virassamy, Megan M. R. O’Malley, Jasmine Kay, Scott N. Mueller, Laura K. Mackay, Roberto Salgado, Sherene Loi
{"title":"Towards targeting the breast cancer immune microenvironment","authors":"Michael A. Harris, Peter Savas, Balaji Virassamy, Megan M. R. O’Malley, Jasmine Kay, Scott N. Mueller, Laura K. Mackay, Roberto Salgado, Sherene Loi","doi":"10.1038/s41568-024-00714-6","DOIUrl":"10.1038/s41568-024-00714-6","url":null,"abstract":"The tumour immune microenvironment is shaped by the crosstalk between cancer cells, immune cells, fibroblasts, endothelial cells and other stromal components. Although the immune tumour microenvironment (TME) serves as a source of therapeutic targets, it is also considered a friend or foe to tumour-directed therapies. This is readily illustrated by the importance of T cells in triple-negative breast cancer (TNBC), culminating in the advent of immune checkpoint therapy in combination with cytotoxic chemotherapy as standard of care for both early and advanced-stage TNBC, as well as recent promising signs of efficacy in a subset of hormone receptor-positive disease. In this Review, we discuss the various components of the immune TME in breast cancer and therapies that target or impact the immune TME, as well as the complexity of host physiology. In this Review, Harris et al. summarize the dynamic changes of the immune breast tumour microenvironment (TME) that take place during disease progression and in response to treatment, and outline emerging therapies to target the immune TME in patients with breast cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 8","pages":"554-577"},"PeriodicalIF":72.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538247","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":"ASS1: Guardian of the genome","authors":"Gabrielle Brewer","doi":"10.1038/s41568-024-00724-4","DOIUrl":"10.1038/s41568-024-00724-4","url":null,"abstract":"Lim et al. show that ASS1, silenced in many cancer types, is a metabolic checkpoint that, following DNA damage, halts cell cycle progression by restricting nucleotide synthesis and p53-related gene transcription.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 8","pages":"521-521"},"PeriodicalIF":72.5,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141538246","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":"Carcinogenesis at single-cell resolution","authors":"Daniela Senft","doi":"10.1038/s41568-024-00722-6","DOIUrl":"10.1038/s41568-024-00722-6","url":null,"abstract":"In this study, Allan Balmain and colleagues used a mouse model to monitor stem cell networks at single-cell resolution during skin carcinogenesis, revealing two cancer stem cell states, rapid cycling and plasticity, between which cells can transition to drive tumour initiation, progression and therapy resistance.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 8","pages":"520-520"},"PeriodicalIF":72.5,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141521382","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":"Preprints as tools to advance careers","authors":"Samantha Hindle, Richard Sever","doi":"10.1038/s41568-024-00718-2","DOIUrl":"10.1038/s41568-024-00718-2","url":null,"abstract":"Preprints benefit researchers’ careers in a number of ways. They allow authors to control the timing of dissemination of their work and provide early evidence of productivity that can be cited in job applications, grant proposals and reviews for tenure and other awards. The practice of posting preprint manuscripts on servers such as bioRxiv has become increasingly common. In this Comment, Hindle and Sever explore the utility of preprints for advancing researchers careers.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 9","pages":"591-592"},"PeriodicalIF":72.5,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492727","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":"Oncologists must act to manage cancer detected through prenatal screening","authors":"Amy E. Turriff, Diana W. Bianchi","doi":"10.1038/s41568-024-00719-1","DOIUrl":"10.1038/s41568-024-00719-1","url":null,"abstract":"The ability of prenatal cell-free DNA sequencing to incidentally detect occult maternal malignancies was first documented over a decade ago, yet coordinated follow-up of pregnant people who receive these results is still lacking in many countries. Here we provide a call to action for oncologists to become more involved in diagnosing and managing these cases.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"24 10","pages":"649-650"},"PeriodicalIF":72.5,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141477010","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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