Nature Reviews Clinical Oncology最新文献

Daratumumab and missed sequencing opportunities in transplant-ineligible multiple myeloma: lessons for future trials 在不适合移植的多发性骨髓瘤中，Daratumumab和错失的测序机会：对未来试验的教训

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-29 DOI: 10.1038/s41571-025-01034-w

Ghulam Rehman Mohyuddin, Aaron M. Goodman

引用次数: 0

Prospective comparisons support the use of navigational bronchoscopy 前瞻性比较支持导航支气管镜检查的使用

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-29 DOI: 10.1038/s41571-025-01039-5

Peter Sidaway

引用次数: 0

Benefit from huCAR19-IL18 cells in patients with CD19+ lymphomas after CAR T cells CAR - T细胞治疗后CD19+淋巴瘤患者获益于huCAR19-IL18细胞

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-23 DOI: 10.1038/s41571-025-01036-8

Diana Romero

引用次数: 0

Tumour and microenvironment crosstalk in NSCLC progression and response to therapy 非小细胞肺癌进展和治疗反应中的肿瘤和微环境串扰

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-16 DOI: 10.1038/s41571-025-01021-1

Zahraa Rahal, Roy El Darzi, Seyed Javad Moghaddam, Tina Cascone, Humam Kadara

{"title":"Tumour and microenvironment crosstalk in NSCLC progression and response to therapy","authors":"Zahraa Rahal, Roy El Darzi, Seyed Javad Moghaddam, Tina Cascone, Humam Kadara","doi":"10.1038/s41571-025-01021-1","DOIUrl":"https://doi.org/10.1038/s41571-025-01021-1","url":null,"abstract":"The treatment landscape of non-small-cell lung cancer (NSCLC) is evolving rapidly, driven by advances in the development of targeted agents and immunotherapies. Despite this progress, some patients have suboptimal responses to treatment, highlighting the need for new therapeutic strategies. In the past decade, the important role of the tumour microenvironment (TME) in NSCLC progression, metastatic dissemination and response to treatment has become increasingly evident. Understanding the complexity of the TME and its interactions with NSCLC can propel efforts to improve current treatment modalities, overcome resistance and develop new treatments, which will ultimately improve the outcomes of patients. In this Review, we provide a comprehensive view of the NSCLC TME, examining its components and highlighting distinct archetypes characterized by spatial niches within and surrounding tumour nests, which form complex neighbourhoods. Next, we explore the interactions within these components, focusing on how inflammation and immunosuppression shape the dynamics of the NSCLC TME. We also address the emerging influences of patient-related factors, such as ageing, sex and health disparities, on the NSCLC–TME crosstalk. Finally, we discuss how various therapeutic strategies interact with and are influenced by the TME in NSCLC. Overall, we emphasize the interconnectedness of these elements and how they influence therapeutic outcomes and tumour progression.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"54 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144066883","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}

引用次数: 0

Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention 肠道微生物群在免疫相关不良事件中的作用：机制和治疗干预

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-14 DOI: 10.1038/s41571-025-01026-w

Ya-Qi Gao, Yong-Jie Tan, Jing-Yuan Fang

{"title":"Roles of the gut microbiota in immune-related adverse events: mechanisms and therapeutic intervention","authors":"Ya-Qi Gao, Yong-Jie Tan, Jing-Yuan Fang","doi":"10.1038/s41571-025-01026-w","DOIUrl":"https://doi.org/10.1038/s41571-025-01026-w","url":null,"abstract":"Immune checkpoint inhibitors (ICIs) constitute a major breakthrough in the field of cancer therapy; their use has resulted in improved outcomes across various tumour types. However, ICIs can cause a diverse range of immune-related adverse events (irAEs) that present a considerable challenge to the efficacy and safety of these treatments. The gut microbiota has been demonstrated to have a crucial role in modulating the tumour immune microenvironment and thus influences the effectiveness of ICIs. Accumulating evidence indicates that alterations in the composition and function of the gut microbiota are also associated with an increased risk of irAEs, particularly ICI-induced colitis. Indeed, these changes in the gut microbiota can contribute to the pathogenesis of irAEs. In this Review, we first summarize the current clinical challenges posed by irAEs. We then focus on reported correlations between alterations in the gut microbiota and irAEs, especially ICI-induced colitis, and postulate mechanisms by which these microbial changes influence the occurrence of irAEs. Finally, we highlight the potential value of gut microbial changes as biomarkers for predicting irAEs and discuss gut microbial interventions that might serve as new strategies for the management of irAEs, including faecal microbiota transplantation, probiotic, prebiotic and/or postbiotic supplements, and dietary modulations.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"4 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945670","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}

引用次数: 0

Targeting the glioblastoma resection margin with locoregional nanotechnologies 局部纳米技术靶向胶质母细胞瘤切除边缘

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-14 DOI: 10.1038/s41571-025-01020-2

Thomas Kisby, Gerben R. Borst, David J. Coope, Kostas Kostarelos

{"title":"Targeting the glioblastoma resection margin with locoregional nanotechnologies","authors":"Thomas Kisby, Gerben R. Borst, David J. Coope, Kostas Kostarelos","doi":"10.1038/s41571-025-01020-2","DOIUrl":"https://doi.org/10.1038/s41571-025-01020-2","url":null,"abstract":"Surgical resection is the first stage of treatment for patients diagnosed with resectable glioblastoma and is followed by a combination of adjuvant radiotherapy and systemic single-agent chemotherapy, which is typically commenced 4–6 weeks after surgery. This delay creates an interval during which residual tumour cells residing in the resection margin can undergo uninhibited proliferation and further invasion, even immediately after surgery, thus limiting the effectiveness of adjuvant therapies. Recognition of the postsurgical resection margin and peri-marginal zones as important anatomical clinical targets and the need to rethink current strategies can galvanize opportunities for local, intraoperative approaches, while also generating a new landscape of innovative treatment modalities. In this Perspective, we discuss opportunities and challenges for developing locoregional therapeutic strategies to target the glioblastoma resection margin as well as emerging opportunities offered by nanotechnology in this clinically transformative setting. We also discuss how persistent barriers to clinical translation can be overcome to offer a potential path forward towards broader acceptability of such advanced technologies.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"44 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143945669","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}

引用次数: 0

Emerging advances and future opportunities in the molecular and therapeutic landscape of anal cancer 肛门癌分子和治疗领域的新进展和未来机遇

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-13 DOI: 10.1038/s41571-025-01025-x

Franz Rödel, Maximilian Fleischmann, Markus Diefenhardt, Hendrik Dapper, Annett Hoffmann, Claus Rödel, Daniel Martin, Emmanouil Fokas

{"title":"Emerging advances and future opportunities in the molecular and therapeutic landscape of anal cancer","authors":"Franz Rödel, Maximilian Fleischmann, Markus Diefenhardt, Hendrik Dapper, Annett Hoffmann, Claus Rödel, Daniel Martin, Emmanouil Fokas","doi":"10.1038/s41571-025-01025-x","DOIUrl":"https://doi.org/10.1038/s41571-025-01025-x","url":null,"abstract":"Anal squamous cell carcinoma (ASCC) is a rare malignancy with an increasing incidence. Primary chemoradiotherapy (CRT) is the standard-of-care treatment for patients with localized ASCC. In the metastatic setting, trials testing immune-checkpoint inhibitor monotherapy have demonstrated outcomes similar to those of patients receiving chemotherapy. Conversely, adding the anti-PD-1 antibody retifanlimab to chemotherapy in patients with recurrent or metastatic ASCC has been shown to significantly improve outcomes. Despite considerable efforts to develop personalized therapy, treatment guidance and prognosis remain reliant on baseline clinical characteristics. An improved understanding of the molecular characteristics of ASCC has provided insights into the mechanisms that mediate tumour progression and response to CRT. For example, human papillomavirus (HPV) infection is known to have an aetiological role in most ASCCs and can modulate cellular responses to CRT via several distinct mechanisms. In this Review, we summarize emerging advances in the molecular and therapeutic landscape of ASCC, including the implementation of biomarkers for treatment guidance and translation into new therapeutic approaches, with HPV infection constituting a global determinant of both tumour biology and clinical outcome. We also discuss the rationale for combining immune-checkpoint inhibitors with CRT in patients with HPV+ tumours.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"58 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939966","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}

引用次数: 0

Promising results with zongertinib in advanced-stage HER2-mutant NSCLC 宗尼替尼治疗晚期her2突变型NSCLC的令人鼓舞的结果

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-13 DOI: 10.1038/s41571-025-01030-0

Diana Romero

{"title":"Promising results with zongertinib in advanced-stage HER2-mutant NSCLC","authors":"Diana Romero","doi":"10.1038/s41571-025-01030-0","DOIUrl":"https://doi.org/10.1038/s41571-025-01030-0","url":null,"abstract":"ERBB2 (commonly known as HER2) is mutated in 2–4% of non-small-cell lung cancers (NSCLCs). The HER2-targeted antibody–drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improves both progression-free survival (PFS) and overall survival in patients with advanced-stage NSCLC harbouring these alterations. However, T-DXd comes with a considerable risk of interstitial lung disease (ILD; including fatal events) and a high risk of grade ≥3 treatment-related adverse events (TRAEs). Now, results from phase Ib of the Beamion LUNG-1 trial show that the HER2-selective tyrosine-kinase inhibitor zongertinib is efficacious and safe in this setting.The results currently presented are from three trial cohorts involving patients with previously treated nonsquamous NSCLC with HER2 mutations that affect either the tyrosine kinase domain (cohorts 1 and 5) or other domains (exploratory cohort 3; n = 20). Patients in cohort 5 (n = 31) had previously received a HER2-targeted ADC. Initially, patients in cohort 1 were randomly assigned to receive zongertinib at a dose of either 120 mg (n = 75) or 240 mg (n = 55), and those in cohorts 3 and 5 received the 240-mg dose. After dose-selection analysis in cohort 1, all patients received 120 mg. Objective response rate (ORR) was the primary end point.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"10 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143939945","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}

引用次数: 0

Next-generation KRAS-G12C inhibitor D3S-001 shows promise 下一代KRAS-G12C抑制剂D3S-001显示出希望

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-09 DOI: 10.1038/s41571-025-01028-8

David Killock

{"title":"Next-generation KRAS-G12C inhibitor D3S-001 shows promise","authors":"David Killock","doi":"10.1038/s41571-025-01028-8","DOIUrl":"https://doi.org/10.1038/s41571-025-01028-8","url":null,"abstract":"The covalent KRAS-G12C inhibitors adagrasib and sotorasib are approved for patients with previously treated KRASG12C-mutant non-small-cell lung cancer (NSCLC) or colorectal cancer (CRC); however, the efficacy of these agents is limited, in large part, by suboptimal target engagement. Now, data from an ongoing single-arm phase I/II trial indicate that D3S-001 (also known as elisrasib), a next-generation KRAS-G12C inhibitor with higher potency, faster target-binding kinetics and thus reduced susceptibility to growth factor-stimulated nucleotide exchange, might have improved antitumour activity.In phase Ia of this trial, 42 patients with previously treated advanced-stage KRASG12C-mutant NSCLC (n = 25), CRC (n = 13) or pancreatic ductal adenocarcinoma (PDAC; n = 4) received D3S-001 at various doses, with primary end points of safety, tolerability, maximum tolerated dose (MTD) and recommended phase II dose (RP2D). D3S-001 was generally well tolerated and had a safety profile similar to that of first-generation KRAS-G12C inhibitors. No dose-limiting toxicities were observed and thus the MTD was not reached. Although 7 patients (16.7%) had grade 3 treatment-related adverse events (TRAEs), these were limited to elevated serum markers or nausea; no grade 4–5 TRAEs occurred. An RP2D of 600 mg was selected on the basis of pharmacokinetics. Among 34 evaluable patients with KRAS-G12C inhibitor-naive disease, the objective response rate (ORR) was 73.5% overall, and it was 66.7%, 88.9% and 75.0% in those with NSCLC, CRC and PDAC, respectively. The disease control rate (DCR) was 97.1%, and the estimated 6-month duration of response (DOR) and progression-free survival (PFS) were 78.4% and 68.6%, respectively.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"44 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143927168","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}

引用次数: 0

Extended neoadjuvant dostarlimab provides durable benefit in resectable dMMR solid tumours 延长新辅助dostarlimumab为可切除的dMMR实体瘤提供持久的益处

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-07 DOI: 10.1038/s41571-025-01027-9

Peter Sidaway

引用次数: 0