Nature Reviews Cancer最新文献

{"title":"AACR 2025","authors":"Daniela Senft","doi":"10.1038/s41568-025-00843-6","DOIUrl":"https://doi.org/10.1038/s41568-025-00843-6","url":null,"abstract":"The 2025 annual meeting of the American Association for Cancer Research (AACR) was held under the theme ‘Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact’. Here, we summarize some key highlights from the meeting.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"6 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260483","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":"Regulatory T cells in the tumour microenvironment","authors":"Charlotte J. Imianowski, Qiang Chen, Creg J. Workman, Dario A. A. Vignali","doi":"10.1038/s41568-025-00832-9","DOIUrl":"https://doi.org/10.1038/s41568-025-00832-9","url":null,"abstract":"<p>The powerful suppressive capabilities of regulatory T (T_reg) cells and their appreciable contribution to tumour progression make them attractive immunotherapeutic targets. However, their role in systemic immune homeostasis makes it important to find ways to specifically target tumour-infiltrating T_reg cells while leaving the wider system unperturbed. It is also unknown whether therapies depleting or disrupting the function of tumour-infiltrating T_reg cells will provide the greatest efficacy while limiting immune-related adverse events. In addition, T_reg cells share much of their biology with conventional CD4⁺ T cells, introducing challenges when designing targeted immunotherapies. In this Review, we discuss recent advances in differentiating tumour-infiltrating T_reg cells from their systemic and tissue-resident counterparts and understanding how the biology of tumour-infiltrating T_reg cells differs from conventional CD4⁺ T cells. We also discuss how recent technological advances may enable the study of tumour-infiltrating T_reg cells in even greater detail, helping to identify new targets for next-generation immunotherapeutic drugs.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"4 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252007","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":"Acquired resistance in cancer: towards targeted therapeutic strategies","authors":"Alice Soragni, Erik S. Knudsen, Thomas N. O’Connor, Cristina E. Tognon, Jeffrey W. Tyner, Beatrice Gini, Donghwa Kim, Trever G. Bivona, Xingxing Zang, Agnieszka K. Witkiewicz, David W. Goodrich, Dadi Jiang, Seth T. Gammon, Christopher D. Willey, Paul C. Boutros, Vlad C. Sandulache, Abdullah A. Osman, Jeffrey N. Myers, Kamiya Mehla, Pankaj K. Singh, Keith S. Chan, Hongbo Gao, Himangi Marathe","doi":"10.1038/s41568-025-00824-9","DOIUrl":"https://doi.org/10.1038/s41568-025-00824-9","url":null,"abstract":"<p>Development of acquired therapeutic resistance limits the efficacy of cancer treatments and accounts for therapeutic failure in most patients. How resistance arises, varies across cancer types and differs depending on therapeutic modalities is incompletely understood. Novel strategies that address and overcome the various and complex resistance mechanisms necessitate a deep understanding of the underlying dynamics. We are at a crucial time when innovative technologies applied to patient-relevant tumour models have the potential to bridge the gap between fundamental research into mechanisms and timing of acquired resistance and clinical applications that translate these findings into actionable strategies to extend therapy efficacy. Unprecedented spatial and time-resolved high-throughput platforms generate vast amounts of data, from which increasingly complex information can be extracted and analysed through artificial intelligence and machine learning-based approaches. This Roadmap outlines key mechanisms that underlie the acquisition of therapeutic resistance in cancer and explores diverse modelling strategies. Clinically relevant, tractable models of disease and biomarker-driven precision approaches are poised to transform the landscape of acquired therapy resistance in cancer and its clinical management. Here, we propose an integrated strategy that leverages next-generation technologies to dissect the complexities of therapy resistance, shifting the paradigm from reactive management to predictive and proactive prevention.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"59 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144201379","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":"Disrupting the balance between activating and inhibitory receptors of γδT cells for effective cancer immunotherapy","authors":"Dennis X. Beringer, Trudy Straetemans, Susana Minguet, Caterina Riillo, Lydia Lynch, Zsolt Sebestyen, Jürgen Kuball","doi":"10.1038/s41568-025-00830-x","DOIUrl":"https://doi.org/10.1038/s41568-025-00830-x","url":null,"abstract":"<p>γδT cell biology in cancer has been studied for decades but remains poorly understood mainly due to species differences in preclinical models and a lack of appropriate analytical tools. This lack of knowledge has hindered the clinical translation of promising therapeutic concepts. In recent years, advanced single-cell analysis techniques and comprehensive protein–protein interaction studies have transformed our understanding of γδT cells and their receptors. This insight has revealed new opportunities and challenges in harnessing γδT cells for therapeutic purposes. In this context, we will discuss the latest findings in γδT cell biology, with a special focus on their role in cancer immune therapies. We will explore strategies to overcome tolerance and shift the balance of γδT cells and their receptors towards antitumour efficacy, which has the potential to successfully translate into various engineering approaches in cancer immunotherapy.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"6 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144192850","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":"Addressing the gaps in cancer screening for LGBTQ+ individuals","authors":"Jenna Davison, Mauricio Jin, Emily Leasure, Victor Chedid","doi":"10.1038/s41568-025-00835-6","DOIUrl":"https://doi.org/10.1038/s41568-025-00835-6","url":null,"abstract":"Individuals of sexual and gender minorities, particularly transgender and non-binary individuals, face substantial disparities in cancer screening owing to stigma, discrimination, provider misconceptions and systemic barriers. Here, we explore these challenges and call for inclusive healthcare practices and policies to ensure equitable access to cancer screening. Individuals of sexual and gender minorities (SGMs), particularly transgender and nonbinary individuals, face substantial disparities in cancer screening. Here, Davison et al. explore these challenges and call for inclusive healthcare practices and policies to ensure equitable access to cancer screening.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"109 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144153480","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":"Revisiting the TGFβ paradox: insights from HPV-driven cancer and the DNA damage response","authors":"Mary Helen Barcellos-Hoff, Sue S. Yom","doi":"10.1038/s41568-025-00819-6","DOIUrl":"https://doi.org/10.1038/s41568-025-00819-6","url":null,"abstract":"<p>The transforming growth factor-β (TGFβ) paradox refers to the well-established role of TGFβ in suppressing cancer in healthy tissues yet promoting malignancy in established cancers. Although this positioned TGFβ inhibitors as a potential therapeutic strategy for malignancy, therapuetic blockade has failed in multiple clinical trials. The general lack of selection principles for defining which patients would most benefit from the addition of a TGFβ inhibitor has probably hindered its deployment. Here, we highlight the therapeutic potential in TGFβ regulation of DNA repair using human papillomavirus (HPV)-driven head and neck squamous cell carcinoma (HNSCC) as an illustrative example. HPV inhibits TGFβ signalling, which in turn reduces DNA damage repair, ultimately conferring sensitivity to cancer treatments and thus contributing to the favourable prognosis of HPV-positive HNSCC. Here, we review the DNA repair deficit caused by a loss of TGFβ signalling and how this could be targeted to induce synthetic lethality. Moreover, we explore its role in predicting response to immune checkpoint inhibitors and the potential of biomarkers to select which patients with cancer could ultimately benefit from TGFβ inhibition.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"131 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144087859","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":"Gender and sex interactions are intrinsic components of cancer phenotypes","authors":"Joshua B. Rubin","doi":"10.1038/s41568-025-00829-4","DOIUrl":"https://doi.org/10.1038/s41568-025-00829-4","url":null,"abstract":"<p>Sex is a significant determinant of cancer incidence and outcome. The effects of sexual differentiation on normal and cancer biology underly this epidemiology. The resultant sex differences in therapeutic target pathways and processes provide a foundation for developing more personalized cancer treatments. However, our efforts at personalization cannot stop there. Humans also have gender, and sex and gender are highly interactive in individuation. Thus, we will also need to consider how gender–sex interactions (GSI) affect cancer biology and clinical parameters such as the timing of diagnoses, clinical trial enrolment, and the completeness of efficacy and toxicity data. Ignoring the effects of GSI can compromise the quality of basic biological and clinical data and the conclusions drawn from them. This is not to say that GSI will always have a significant effect or any effect at all in every cancer study. Rather, it is to say that we know enough about GSI and human cancer to anticipate measurable differences when GSI are considered in research, enabling us to experimentally determine whether their effects are significant. Here, I delve deeply into GSI and cancer, as this approach to treatment personalization holds great promise to benefit all patients with cancer.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"40 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144096865","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":"Recent advances in therapeutic cancer vaccines","authors":"Neeha Zaidi, Elizabeth M. Jaffee, Mark Yarchoan","doi":"10.1038/s41568-025-00820-z","DOIUrl":"https://doi.org/10.1038/s41568-025-00820-z","url":null,"abstract":"<p>The success of cancer prevention vaccines targeting cancer-causing viruses has drastically reduced cancer mortality worldwide. However, the development of therapeutic cancer vaccines, which aim to elicit an immune response directly against cancer cells, has faced notable clinical setbacks. In this Review, we explore lessons learned from past cancer vaccine trials and how the field has progressed into an era of renewed promise. Previous vaccines primarily targeted tumour-associated antigens and were mainly tested as monotherapies in late-stage cancers. In contrast, contemporary vaccines focus on targeting tumour-specific antigens (neoantigens) and are showing initial evidence of clinical efficacy, particularly in early-stage cancers and precancers when combined with immune checkpoint inhibitors. Advances in tumour profiling and novel vaccine platforms have enhanced vaccine specificity and potency. We discuss recent clinical trials of therapeutic cancer vaccines and outline future directions for the field.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"57 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066158","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":"Reply to ‘Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies’","authors":"Sylvain Peuget, Galina Selivanova","doi":"10.1038/s41568-025-00825-8","DOIUrl":"https://doi.org/10.1038/s41568-025-00825-8","url":null,"abstract":"<p>We thank Wu et al. for their comments on our Review (Peuget, S., Zhou, X. &amp; Selivanova, G. Translating p53-based therapies for cancer into the clinic. <i>Nat. Rev. Cancer</i> <b>24</b>, 192–215 (2024))¹; they raise some interesting points that we respond to below (Wu, J., Song, H., Xiao, S. &amp; Lu, M. Heterogeneity of <i>TP53</i> mutations necessitates differentiation with p53-rescue therapies. <i>Nat. Rev. Cancer</i> https://doi.org/10.1038/s41568-025-00826-7 (2025))².</p><p>Approximately half of all human cancers express mutants of the tumour suppressor p53, with loss of function owing to just a single amino acid residue substitution. These p53 mutants, often overexpressed, could be regarded as a loaded gun — but with a jammed trigger. As we outlined in our Review¹, this makes the idea of a cancer therapy strategy aimed at restoring wild-type p53 tumour-suppressor function to mutant p53 a very attractive goal. However, despite considerable research efforts, the field has yet to produce clinical advancements based on mutant p53 restoration.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"4 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066155","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":"Heterogeneity of TP53 mutations necessitates differentiation with p53-rescue therapies","authors":"Jiaqi Wu, Huaxin Song, Shujun Xiao, Min Lu","doi":"10.1038/s41568-025-00826-7","DOIUrl":"https://doi.org/10.1038/s41568-025-00826-7","url":null,"abstract":"<p>We read with interest the Review by Peuget et al. (Peuget, S., Zhou, X. &amp; Selivanova, G. Translating p53-based therapies for cancer into the clinic. <i>Nat. Rev. Cancer</i> <b>24</b>, 192–215 (2024))¹ that introduces the development of p53-based therapies. We fully agree with the tremendous clinical value of p53-targeting drugs, as <i>TP53</i> is the most commonly mutated gene in cancer¹. However, we would like to point out that the descriptions of small-molecule compounds that can rescue two or more different types of p53 mutant need to be given with extreme caution. Of the 23 registered p53-rescue trials, 17 trials are investigating these compounds in over 1,000 patients with cancer without differentiating the <i>TP53</i> mutations (Supplementary Table 1).</p><p>Small-molecule compounds that bind mutant p53 and restore its tumour-suppressive function have been extensively pursued over the past decades, with at least 71 rescue compounds identified^2,3,4. The majority of these are termed generic rescue compounds and can rescue numerous mutants simultaneously, spawning hundreds of basic and clinical studies using these compounds to rescue arbitrarily selected p53 mutants. However, based on the logic derived from the diverse mechanisms of action of p53 mutants (Fig. 1b) and increasing experimental validations^5,6,7, a consensus is forming that no generic rescue compound can provide a ‘one-size-fits-all’ solution to rescue two or more types of p53 mutant. For example, a p53-thermostabilizing compound can shift the ‘unfolding–folding’ dynamic balance towards folding, thereby promoting the refolding of structural mutants and rescuing them. Thus, such a compound is both mechanistically and experimentally validated as ineffective in rescuing p53 truncation mutants that lack large stretches of amino acids, or DNA-contact mutants that lack DNA-binding amino acids^5,6,7. Similarly, a DNA-contact mutant-rescue compound (if one were to exist) should act by compensating for the lost DNA-binding amino acids and, thus, mechanistically could not rescue structural mutants, which are unfolded.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"33 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066156","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}