Nature Reviews Clinical Oncology最新文献

{"title":"Reduced-volume radiotherapy for locally advanced NPC improves QOL without compromising efficacy","authors":"David Killock","doi":"10.1038/s41571-025-01014-0","DOIUrl":"https://doi.org/10.1038/s41571-025-01014-0","url":null,"abstract":"<p>Induction chemotherapy (IC) followed by concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma (NPC). Most patients have considerable tumour shrinkage after IC, yet the radiotherapy target volume is calculated on the basis of the dimensions of the pretreatment tumour, which can result in debilitating toxicities owing to irradiation of surrounding functional structures. Now, data from a phase III trial demonstrate that reducing the radiation volume according to tumour shrinkage maintains local control and improves quality of life (QOL).</p><p>In this trial, 445 patients with previously untreated stage III–IVA NPC who had completed 3 cycles of gemcitabine–cisplatin IC were randomly assigned (1:1) to receive radiotherapy based on the post-IC versus pre-IC tumour volume, plus 2 or 3 cycles of concurrent cisplatin. For both groups, any areas of bony structural invasion observed prior to IC were included in the target volume, regardless of changes after IC. Non-inferior locoregional relapse-free survival (LRFS) was the primary end point.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"68 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143589669","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":"Hodgkin lymphoma: great progress with room for improvement","authors":"Paul J. Bröckelmann","doi":"10.1038/s41571-025-01012-2","DOIUrl":"https://doi.org/10.1038/s41571-025-01012-2","url":null,"abstract":"First-line treatment of advanced-stage classic Hodgkin lymphoma (HL) has successfully entered the era of targeted agents based on results from the phase III German Hodgkin Study Group HD21 and US intergroup S1826 trials. Although these trials bring about important advances, many uncertainties remain and the outcomes of all patients with HL can be further improved.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"31 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583100","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":"MORPHEUS-Liver provides a way forward in expanding the immunotherapy options for hepatocellular carcinoma","authors":"Bruno Sangro, Josepmaria Argemí","doi":"10.1038/s41571-025-01009-x","DOIUrl":"https://doi.org/10.1038/s41571-025-01009-x","url":null,"abstract":"Advanced-stage hepatocellular carcinoma is currently treated with various anti-PD-(L)1 antibody-containing regimens. Now, a triplet combining the anti-TIGIT antibody tiragolumab with one of these regimens has demonstrated promising efficacy in a phase Ib/II trial, although these data will need to be confirmed. This study highlights the value of umbrella trials while also raising questions regarding the most effective immune-targeting strategies in patients with this disease.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"4 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143583099","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":"SOX superior to CAPOX in resectable G/GEJ cancer","authors":"Peter Sidaway","doi":"10.1038/s41571-025-01010-4","DOIUrl":"https://doi.org/10.1038/s41571-025-01010-4","url":null,"abstract":"<p>Most patients undergoing surgery for locally advanced gastric or gastroesophageal junction (G/GEJ) cancer will require chemotherapy; however, the optimum approach, including the most effective regimen and whether perioperative chemotherapy is more effective than an adjuvant-only approach, remains uncertain. Now, 5-year follow-up data from the phase III RESOLVE trial provide evidence supporting the use of adjuvant S-1 plus oxaliplatin (SOX) in these patients.</p><p>A total of 1,094 patients with histologically confirmed cT4a N+ M0 or cT4b any N-stage M0 G/GEJ adenocarcinoma were randomly assigned (1:1:1) to receive either adjuvant SOX, adjuvant capecitabine plus oxaliplatin (CAPOX), or perioperative SOX. This study was conducted at 27 hospitals across China. Disease-free survival (DFS) at 3 years was the primary end point and was described in a previous report.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"53 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143560614","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":"Enhancing immunotherapy with tumour-responsive nanomaterials","authors":"Stephen W. Linderman,&nbsp;Louis DeRidder,&nbsp;Lucía Sanjurjo,&nbsp;Michael B. Foote,&nbsp;María José Alonso,&nbsp;Ameya R. Kirtane,&nbsp;Robert Langer,&nbsp;Giovanni Traverso","doi":"10.1038/s41571-025-01000-6","DOIUrl":"10.1038/s41571-025-01000-6","url":null,"abstract":"The targeted delivery of immunotherapies to tumours using tumour-responsive nanomaterials is a promising area of cancer research with the potential to address the limitations of systemic administration such as on-target off-tumour toxicities and a lack of activity owing to the immunosuppressive tumour microenvironment (TME). Attempts to address these challenges include the design and functionalization of nanomaterials capable of releasing their cargoes in response to specific TME characteristics, thus facilitating the targeted delivery of immune-checkpoint inhibitors, cytokines, mRNAs, vaccines and, potentially, chimaeric antigen receptors as well as of agents that modulate the extracellular matrix and induce immunogenic cell death. In this Review, we describe these various research efforts in the context of the dynamic properties of the TME, such as pH, reductive conditions, reactive oxygen species, hypoxia, specific enzymes, high levels of ATP and locoregional aspects, which can be leveraged to enhance the specificity and efficacy of nanomaterial-based immunotherapies. Highlighting preclinical successes and ongoing clinical trials, we evaluate the current landscape and potential of these innovative approaches. We also consider future research directions as well as the most important barriers to successful clinical translation, emphasizing the transformative potential of tumour-responsive nanomaterials in overcoming the barriers that limit the activity of traditional immunotherapies, thus improving patient outcomes. Immunotherapies, predominantly immune-checkpoint inhibitors and chimaeric antigen receptor T cells, have transformed oncology. Nonetheless, these systemically administered agents have several limitations, including the risk of off-target toxicities and a lack of activity owing to an inability to overcome an immunosuppressive tumour microenvironment (TME). In this Review, the authors describe the potential to overcome these challenges using functionalized nanomaterials that are designed to release a wide range of immunotherapeutic cargoes in response to specific TME characteristics, including hypoxia, differences in pH, the presence of specific enzymes, reactive oxygen species and/or high levels of extracellular ATP.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"262-282"},"PeriodicalIF":81.1,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143561283","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":"Will I feel better? Raising the bar for quality of life in oncology","authors":"Ariadna Tibau,&nbsp;Alejandra Romano,&nbsp;Aaron S. Kesselheim","doi":"10.1038/s41571-025-01002-4","DOIUrl":"10.1038/s41571-025-01002-4","url":null,"abstract":"Patients with advanced-stage cancer seek treatments that prolong survival and improve quality of life. We analysed new anticancer drug indications approved by the FDA and EMA between 2020 and 2023 using the European Society for Medical Oncology-Magnitude of Clinical Benefit Scale quality-of-life checklist. Our findings highlight critical gaps in the availability and reliability of quality-of-life outcomes from the pivotal trials that support these approvals.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 4","pages":"235-236"},"PeriodicalIF":81.1,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143517865","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 clinical applications of single-cell RNA sequencing in oncology","authors":"Emily Boxer, Nisan Feigin, Roi Tschernichovsky, Noam Galili Darnell, Alissa R. Greenwald, Rouven Hoefflin, Daniel Kovarsky, Dor Simkin, Shira Turgeman, Lingling Zhang, Itay Tirosh","doi":"10.1038/s41571-025-01003-3","DOIUrl":"https://doi.org/10.1038/s41571-025-01003-3","url":null,"abstract":"<p>Single-cell RNA sequencing (scRNA-seq) has revolutionized our understanding of complex tissues both in health and in disease. Over the past decade, scRNA-seq has been applied to tumour samples obtained from patients with cancer in hundreds of studies, thereby advancing the view that each tumour is a complex ecosystem and uncovering the diverse states of both cancer cells and the tumour microenvironment. Such studies have primarily investigated and provided insights into the basic biology of cancer, although considerable research interest exists in leveraging these findings towards clinical applications. In this Review, we summarize the available data from scRNA-seq studies investigating samples from patients with cancer with a particular focus on findings that are of potential clinical relevance. We highlight four main research objectives of scRNA-seq studies and describe some of the most relevant findings towards such goals. We also describe the limitations of scRNA-seq, as well as future approaches in this field that are anticipated to further advance clinical applicability.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"54 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143518494","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":"Using oncolytic viruses to induce hyperacute rejection against cancer","authors":"Howard L. Kaufman, Ann W. Silk","doi":"10.1038/s41571-025-01006-0","DOIUrl":"https://doi.org/10.1038/s41571-025-01006-0","url":null,"abstract":"In a recently reported study, a novel engineered oncolytic Newcastle disease virus encoding porcine α1,3-galactosyltransferase was evaluated in monkeys with CRISPR-induced primary hepatocellular carcinoma and in a phase I clinical trial. The virus induced hyperacute tumour rejection and an objective response rate of 35% in 20 evaluable patients. This approach highlights the promises and challenges of oncolytic virus drug development.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"68 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143495365","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 SONIA trial shows the power and challenges of academic research","authors":"Shani Paluch-Shimon, Fatima Cardoso","doi":"10.1038/s41571-025-01004-2","DOIUrl":"https://doi.org/10.1038/s41571-025-01004-2","url":null,"abstract":"The thought-provoking SONIA trial showed that patients with hormone receptor-positive, HER2-negative advanced-stage breast cancer receiving deferred (second-line) versus first-line cyclin dependent-kinase (CDK) 4/6 inhibitors have noninferior progression-free survival after second-line treatment; such an approach also results in substantial cost savings. Herein, we discuss some important limitations of this trial and argue that, owing to their effect on overall survival, CDK4/6 inhibitors should remain the standard-of-care first-line therapy.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"22 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477533","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":"Zenocutuzumab shows efficacy in NRG1 fusion-positive solid tumours","authors":"Diana Romero","doi":"10.1038/s41571-025-01005-1","DOIUrl":"https://doi.org/10.1038/s41571-025-01005-1","url":null,"abstract":"<p>Chimeric proteins resulting from fusions involving <i>NRG1</i>, which encodes a growth factor from the EGF family, promote HER2–HER3 heterodimerization and subsequent oncogenic activation of cell proliferation. These fusions occur in &lt;1% of solid tumours including non-small-cell lung cancer (NSCLC) and pancreatic adenocarcinoma (PDAC). Now, data from the phase II eNRGy trial demonstrate that the HER2 × HER3 bispecific antibody zenocutuzumab is efficacious and safe in patients with advanced-stage <i>NRG1</i> fusion-positive solid tumours.</p><p>The primary efficacy population comprised 158 patients with one of ten solid tumour types, primarily NSCLC (<i>n</i> = 94) and PDAC (<i>n</i> = 36). Most patients had received previous systemic therapy for metastatic disease, including 77% and 92% of those with NSCLC and PDAC, respectively. The primary end point was objective response rate (ORR).</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"2 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143451475","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}