Nature Reviews Cancer最新文献

{"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}

{"title":"Deep tissue imaging of cancer in the infrared","authors":"Ali Yasin Sonay","doi":"10.1038/s41568-025-00823-w","DOIUrl":"https://doi.org/10.1038/s41568-025-00823-w","url":null,"abstract":"Ali Sonay describes the development of an image-guided surgical approach that uses a commercially available dye, CJ215, to improve the real-time detection and precise removal of cancerous tissues and for better preclinical visualization of cancer progression in deep tissues.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"70 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143880638","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":"Targeted protein degradation for cancer therapy","authors":"Matthias Hinterndorfer, Valentina A. Spiteri, Alessio Ciulli, Georg E. Winter","doi":"10.1038/s41568-025-00817-8","DOIUrl":"https://doi.org/10.1038/s41568-025-00817-8","url":null,"abstract":"<p>Targeted protein degradation (TPD) aims at reprogramming the target specificity of the ubiquitin–proteasome system, the major cellular protein disposal machinery, to induce selective ubiquitination and degradation of therapeutically relevant proteins. Since its conception over 20 years ago, TPD has gained a lot of attention mainly due to improvements in the design of bifunctional proteolysis targeting chimeras (PROTACs) and understanding the mechanisms underlying molecular glue degraders. Today, PROTACs are on the verge of a first clinical approval and recent structural and mechanistic insights combined with technological leaps promise to unlock the rational design of protein degraders, following the lead of lenalidomide and related clinically approved analogues. At the same time, the TPD universe is expanding at a record speed with the discovery of novel modalities beyond molecular glue degraders and PROTACs. Here we review the recent progress in the field, focusing on newly discovered degrader modalities, the current state of clinical degrader candidates for cancer therapy and upcoming design approaches.</p>","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"91 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143875881","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":"Androgen receptor activation for breast cancer therapy","authors":"Dimple Notani","doi":"10.1038/s41568-025-00821-y","DOIUrl":"https://doi.org/10.1038/s41568-025-00821-y","url":null,"abstract":"In this Journal Club, Dimple Notani discusses a study that demonstrates a tumour suppressive function of the androgen receptor in oestrogen receptor-positive breast cancer.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"529 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143866328","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":"Measuring HLA disruption using MHC Hammer","authors":"Clare Puttick","doi":"10.1038/s41568-025-00822-x","DOIUrl":"https://doi.org/10.1038/s41568-025-00822-x","url":null,"abstract":"In this Tools of the Trade article, Clare Puttick describes the development of MHC Hammer, a computational tool that uses whole-exome sequencing and RNA sequencing data for measuring HLA disruption.","PeriodicalId":19055,"journal":{"name":"Nature Reviews Cancer","volume":"232 1","pages":""},"PeriodicalIF":78.5,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143862199","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}