Nature Reviews Clinical Oncology最新文献

{"title":"The microbiota in radiotherapy-induced cancer immunosurveillance","authors":"Jianzhou Chen, Eric Deutsch, Guido Kroemer, Lorenzo Galluzzi, Laurence Zitvogel","doi":"10.1038/s41571-025-01052-8","DOIUrl":"https://doi.org/10.1038/s41571-025-01052-8","url":null,"abstract":"<p>Radiotherapy has an established role in the clinical treatment of patients with a variety of cancers owing to the ability to preferentially kill malignant cells mostly while sparing their non-malignant counterparts. Results from phase I–II trials also suggest that radiotherapy can have therapeutically relevant immunostimulatory effects, especially when combined with immune-checkpoint inhibitors. Over the past two decades, evidence has emerged showing that intestinal microbial communities have a major influence on the immunological tonus of patients with cancer and can influence sensitivity to various immunotherapies, including immune-checkpoint inhibitors and chimeric antigen receptor T cells. Here, we critically discuss the effects of such microbial ecosystems on radiotherapy-induced toxicities and tumour-targeting immune responses, with a focus on the clinical potential of these relationships for predictive and therapeutic clinical applications.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"87 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144629608","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":"Therapeutic targeting of mismatch repair-deficient cancers","authors":"Paul Johannet, Benoit Rousseau, Carol Aghajanian, Michael B. Foote, Luis A. Diaz","doi":"10.1038/s41571-025-01054-6","DOIUrl":"https://doi.org/10.1038/s41571-025-01054-6","url":null,"abstract":"<p>DNA mismatch repair (MMR) is one of many evolutionarily conserved processes that act as guardians of genomic integrity. MMR proteins recognize errors that occur during DNA replication and initiate countermeasures to rectify those mistakes. MMR deficiency (MMRd) therefore leads to a dramatic accumulation of mutations. The MMRd genomic signature is characterized by a high frequency of single-base substitutions as well as insertions and/or deletions that preferentially occur in short nucleotide repeat sequences known as microsatellites. This accumulation leads to a phenomenon termed microsatellite instability, which accordingly serves as a marker of underlying MMRd. MMRd is associated with hereditary cancer syndromes such as Lynch syndrome and constitutional MMRd as well as with sporadic tumour development across a variety of tissues. High baseline immune cell infiltration is a characteristic feature of MMRd/microsatellite instability-high tumours, as is the upregulation of immune checkpoints. Importantly, the molecular profile of MMRd tumours confers remarkable sensitivity to immune-checkpoint inhibitors (ICIs). Many patients with MMRd disease derive durable clinical benefit when treated with these agents regardless of the primary tumour site. Nevertheless, a substantial subset of these patients will fail to respond to ICI, and increasing research is focused on identifying the factors that confer resistance. In this Review, we begin by discussing the biological function of the MMR machinery as well as the genomic sequelae of MMRd before then examining the clinical implications of MMRd with a specific focus on cancer predisposition, diagnostic approaches, therapeutic strategies and potential mechanisms of resistance to ICIs.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"21 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594119","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":"EHA–EMN Evidence-Based Guidelines for diagnosis, treatment and follow-up of patients with multiple myeloma","authors":"Meletios A. Dimopoulos, Evangelos Terpos, Mario Boccadoro, Philippe Moreau, María-Victoria Mateos, Sonja Zweegman, Gordon Cook, Monika Engelhardt, Michel Delforge, Roman Hajek, Fredrik Schjesvold, Francesca Gay, Salomon Manier, Katja C. Weisel, Martin Kaiser, Niels W. C. J. van de Donk, Elena Zamagni, Paula Rodriguez-Otero, Aurore Perrot, Christoph Driessen, Jelena Bila, Edward Laane, Dominik Dytfeld, Cyrille Touzeau, Meral Beksac, Marc S. Raab, Michele Cavo, Mohamad Mohty, Andrew Spencer, Heinz Ludwig, Hermann Einsele, Jesus San-Miguel, Pieter Sonneveld","doi":"10.1038/s41571-025-01041-x","DOIUrl":"https://doi.org/10.1038/s41571-025-01041-x","url":null,"abstract":"<p>Since the publication in 2021 of the European Hematology Association (EHA) Clinical Practice Guidelines for the treatment of patients with smouldering multiple myeloma (SMM) and multiple myeloma (MM), developed in collaboration with the European Society for Medical Oncology, a novel international staging system (R2-ISS) has been developed, several prognostic factors are entering clinical practice (such as minimal residual disease, circulating plasma cells and monoclonal protein assessed by mass spectrometry) and, at the time of writing, 14 novel regimens have been approved by the EMA and/or the FDA for the treatment of patients with MM. A multidisciplinary group of experts from the EHA and European Myeloma Network, based in various institutions mostly located in Europe, have updated the previous guidelines and produced algorithms for everyday clinical practice that incorporate levels of evidence and grades of recommendation based on the aforementioned new data. In these Evidence-Based Guidelines, we provide key treatment recommendations for both patients with newly diagnosed MM and those with relapsed and/or refractory MM, including guidance for the use of established drugs as well as contemporary immunotherapies. Novel approaches for the management of patients with SMM focus on those who might require early intervention. Finally, we provide recommendations for myeloma-related complications and adverse events, such as bone disease, renal impairment and infections, as well as for those associated with T cell-mobilizing therapies, such as cytokine-release syndrome and immune effector cell-associated neurotoxicity syndrome.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"65 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568754","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":"Perioperative pembrolizumab demonstrates clinical benefit in locally advanced HNSCC","authors":"David Killock","doi":"10.1038/s41571-025-01057-3","DOIUrl":"https://doi.org/10.1038/s41571-025-01057-3","url":null,"abstract":"<p>Immune-checkpoint inhibitors (ICIs) have been established as a key component of therapy for recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). However, most patients with HNSCC present with locally advanced disease, and initial efforts to integrate ICIs concurrent with or following curative-intent local treatment have produced disappointing results. Now, data from the phase III KEYNOTE-689 trial indicate that a perioperative approach improves outcomes in this setting.</p><p>In KEYNOTE-689, 714 patients with newly diagnosed, resectable stage III–IVA HNSCC (laryngeal, hypopharyngeal, oropharyngeal or in the oral cavity) were randomly assigned (1:1) to undergo standard surgery and adjuvant (chemo)radiotherapy with versus without 2 neoadjuvant and 15 adjuvant cycles of pembrolizumab. The primary end point was event-free survival (EFS) sequentially assessed in the PD-L1 combined positive score (CPS) ≥10 subgroup (<i>n</i> = 465; 65.1%), the PD-L1 CPS ≥1 subgroup (<i>n</i> = 682; 95.5%), and then in the entire cohort.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"654 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144546900","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":"A new first-line option for advanced-stage anal squamous cell carcinoma","authors":"Diana Romero","doi":"10.1038/s41571-025-01056-4","DOIUrl":"https://doi.org/10.1038/s41571-025-01056-4","url":null,"abstract":"<p>The combination of carboplatin plus docetaxel is the standard-of-care first-line treatment for patients with anal squamous cell carcinoma (ASCC) in the recurrent or metastatic setting, although this regimen provides limited survival benefit and quality of life remains poor. Now, results from the phase III POD1UM-303/InterAACT-2 trial demonstrate the efficacy and safety of adding the anti-PD-1 antibody retifanlimab to first-line chemotherapy in this setting.</p><p>A total of 308 patients with locally recurrent or metastatic ASCC were randomly allocated (1:1) to receive first-line carboplatin–docetaxel (6 cycles) plus either retifanlimab or placebo for up to 1 year. Progression-free survival (PFS) was the primary end point.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"47 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144520877","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":"Role of novel immunotherapy combinations in the management of advanced-stage hepatocellular carcinoma","authors":"Josep M. Llovet","doi":"10.1038/s41571-025-01055-5","DOIUrl":"https://doi.org/10.1038/s41571-025-01055-5","url":null,"abstract":"Immune-checkpoint inhibitors have revolutionized the management of hepatocellular carcinoma. Currently, anti-PD-(L)-1 antibodies combined with either bevacizumab or anti-CTLA4 antibodies are the standard of care for advanced-stage tumours. Now, two phase III studies (CheckMate 9DW and APOLLO) have reported positive survival results in the first-line setting, although with distinct implications for clinical practice.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"656 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144515543","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":"Ecological management of the microbiota in patients with cancer","authors":"Joao B. Xavier","doi":"10.1038/s41571-025-01049-3","DOIUrl":"https://doi.org/10.1038/s41571-025-01049-3","url":null,"abstract":"<p>The composition of the intestinal microbiota influences the outcomes of patients receiving cancer treatment, although the best way to use this knowledge to improve cancer care remains unclear. In this Review, I synthesize the current understanding of host–microbiota dynamics in patients with cancer, and propose the integration of microbiota management guided by ecological principles in cancer care. Ecological management of the microbiota emphasizes the preservation of microbial populations — and the benefits they provide to the host — from the disruption caused by treatments such as chemotherapy and prophylactic antibiotics. The microbiota can be routinely and longitudinally monitored in patients using proven non-invasive methods, such as 16S ribosomal RNA amplicon sequencing. Longitudinal microbiome data can be processed with innovative computational tools based on principles of mathematical ecology to predict the risk of microbiota-related complications, guide treatment choices that minimize disturbance to the microbiota and restore microbial populations damaged by cancer treatment. Routine microbiome monitoring could also generate extensive datasets for human-based research, which could inform new microbiota-targeted interventions that improve responses to cancer treatments, including immune-checkpoint inhibitors. Applying ecological approaches to manage microbiota could enhance cancer care and improve patient outcomes.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"18 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144500610","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":"From ASCO 2025","authors":"Diana Romero","doi":"10.1038/s41571-025-01053-7","DOIUrl":"https://doi.org/10.1038/s41571-025-01053-7","url":null,"abstract":"<p>As is usual during the first week of June, the clinical oncology community gathered together for the ASCO Annual Meeting. The overarching theme of this year’s meeting was ‘driving knowledge to action: building a better future’. In the Opening Session, the CEO of ASCO, Clifford Hudis, elaborated on this motto, bringing attention to the unprecedented challenges that researchers in the USA are facing owing to budget uncertainty. This message was subsequently echoed by other presenters in several sessions.</p><p>The Plenary Session featured phase III trials across several cancer types, including polycythaemia vera. Patients with this haematological condition have a high risk of thrombosis and leukaemias. Their management typically involves frequent phlebotomy, which greatly compromises quality of life. In VERIFY, 293 patients with polycythaemia vera requiring frequent phlebotomy with or without stable cytoreductive therapy were randomly allocated (1:1) to receive the hepcidin mimetic peptide rusfertide versus placebo. Clinical response, a composite end point reflecting a decreased need for phlebotomy, was more common in patients receiving rusfertide (76.9% versus 32.9%; <i>P</i> &lt; 0.0001). In ATOMIC, 712 patients with resected stage III mismatch repair-deficient (dMMR) colon adenocarcinomas were randomly allocated (1:1) to receive adjuvant mFOLFOX6 either alone or in combination with atezolizumab. The addition of atezolizumab improved disease-free survival (DFS; 86.4% versus 76.6 %; HR 0.50, 95% CI 0.35–0.72; <i>P</i> &lt; 0.0001). Grade ≥3 adverse events (AEs) occurred in 71.7% versus 62.1% of patients. In NIVOSTOP, 680 patients with high-risk resected locally advanced head and neck squamous cell carcinomas (SCCs) were randomly allocated (1:1) to receive standard-of-care (SOC) chemoradiotherapy either alone or in combination with nivolumab. The addition of nivolumab improved DFS (63.1% versus 52.5% without nivolumab; HR 0.76, 95% CI 0.60–0.98; <i>P</i> = 0.034). Grade ≥4 AEs occurred in 13.7% versus 6.3% of patients. The programme chairs are to be applauded for inviting the cancer survivor and physician Mark Lewis to discuss the studies presented in the Plenary Session from his perspective. Without dismissing the importance of numeric end points, Lewis highlighted the importance of qualitative assessments of trial outcomes to many patients and their families.</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"51 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144341224","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":"Zanidatamab shows promise as first-line therapy for advanced-stage HER2+ GEA","authors":"David Killock","doi":"10.1038/s41571-025-01048-4","DOIUrl":"https://doi.org/10.1038/s41571-025-01048-4","url":null,"abstract":"<p>Trastuzumab plus platinum–fluoropyrimidine chemotherapy has been the backbone of frontline therapy for advanced-stage HER2-positive gastroesophageal adenocarcinoma (HER2⁺ GEA) since 2010 on the basis of results from the landmark phase III ToGA trial. Now, data from a phase II trial indicate that zanidatamab, a biparatopic antibody targeting two distinct epitopes of HER2, might improve outcomes in this setting.</p><p>In this single-arm trial, patients with previously untreated advanced-stage HER2⁺ GEA received zanidatamab in combination with either 5-fluorouracil, folinic acid and oxaliplatin (<i>n</i> = 24), capecitabine and oxaliplatin (<i>n</i> = 20), or 5-fluorouracil and cisplatin (<i>n</i> = 2). The primary end point was confirmed objective response rate (ORR).</p>","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"19 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311789","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":"Robot-assisted laparoscopic surgery confers improved oncological outcomes.","authors":"Peter Sidaway","doi":"10.1038/s41571-025-01050-w","DOIUrl":"https://doi.org/10.1038/s41571-025-01050-w","url":null,"abstract":"","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"623 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144311325","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}