Nature Reviews Cancer最新文献

{"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}

{"title":"Ageing lipids map melanoma’s journey","authors":"Gabrielle Brewer","doi":"10.1038/s41568-025-00833-8","DOIUrl":"https://doi.org/10.1038/s41568-025-00833-8","url":null,"abstract":"Melanoma exhibits distinct patterns of organ-specific spread. Now, Gurung et al. find that age-based variations in stromal lipid species dictate melanoma metastatic tropism to the liver.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"43 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143979402","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":"How cancer reduces motivation","authors":"Daniela Senft","doi":"10.1038/s41568-025-00834-7","DOIUrl":"https://doi.org/10.1038/s41568-025-00834-7","url":null,"abstract":"In addition to its physical symptoms, cancer cachexia — a severe wasting syndrome — also leads to fatigue, apathy and depression. A recent study published in Science identifies neural circuit mechanisms that underlie these motivational symptoms.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"29 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945860","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":"NOTUM-mediated stem cell competition in CRC","authors":"Praver Gupta, Tamal Das","doi":"10.1038/s41568-025-00827-6","DOIUrl":"https://doi.org/10.1038/s41568-025-00827-6","url":null,"abstract":"In this Journal Club. Gupta and Das discuss a study demonstrating how Apc-deficient intestinal stem cells (ISCs) gain a competitive advantage over normal ISCs through the upregulation of NOTUM.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"79 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933458","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":"Digitally enhanced Raman spectroscopy","authors":"Xinyuan Bi","doi":"10.1038/s41568-025-00828-5","DOIUrl":"https://doi.org/10.1038/s41568-025-00828-5","url":null,"abstract":"In this Tools of the Trade article, Xinyuan Bi describes the development of digital colloid-enhanced Raman spectroscopy (dCERS), a method that addresses the reproducibility issues of surface-enhanced Raman spectroscopy (SERS) at ultra-low concentrations by using single-molecule counting.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"123 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-05-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143933462","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}