Nature Reviews Clinical Oncology最新文献_第4页

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

Improving outcomes of patients with pancreatic cancer. 改善胰腺癌患者的预后。

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-06 DOI: 10.1038/s41571-025-01019-9

Stephan B Dreyer,Philip Beer,Sunil R Hingorani,Andrew V Biankin

{"title":"Improving outcomes of patients with pancreatic cancer.","authors":"Stephan B Dreyer,Philip Beer,Sunil R Hingorani,Andrew V Biankin","doi":"10.1038/s41571-025-01019-9","DOIUrl":"https://doi.org/10.1038/s41571-025-01019-9","url":null,"abstract":"Research studies aimed at improving the outcomes of patients with pancreatic ductal adenocarcinoma (PDAC) have brought about limited progress, and in clinical practice, the optimized use of surgery, chemotherapy and supportive care have led to modest improvements in survival that have probably reached a plateau. As a result, PDAC is expected to be the second leading cause of cancer-related death in Western societies within a decade. The development of therapeutic advances in PDAC has been challenging owing to a lack of actionable molecular targets, a typically immunosuppressive microenvironment, and a disease course characterized by rapid progression and clinical deterioration. Yet, the progress in our understanding of PDAC and identification of novel therapeutic opportunities over the past few years is leading to a strong sense of optimism in the field. In this Perspective, we address the aforementioned challenges, including biological aspects of PDAC that make this malignancy particularly difficult to treat. We explore specific areas with potential for therapeutic advances, including targeting mutant KRAS, novel strategies to harness the antitumour immune response and approaches to early detection, and propose mechanisms to improve clinical trial design and to overcome various community and institutional barriers to progress.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"38 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143914984","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

The evolving immuno-angiogenic paradigm in NSCLC: lessons from ivonescimab 非小细胞肺癌中不断发展的免疫血管生成模式：来自ivonescimab的经验教训

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-06 DOI: 10.1038/s41571-025-01024-y

Roy S. Herbst, Lieping Chen

引用次数: 0

Less-frequent surveillance is noninferior to annual mammography. 监测频率较低的乳房 X 射线照相术并不比每年一次的乳房 X 射线照相术效果差。

IF 81.1 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-05-01 DOI: 10.1038/s41571-025-01001-5

Peter Sidaway

引用次数: 0

Durable responses to belzutifan in patients with VHL disease VHL患者对贝祖替芬的持久反应

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-04-25 DOI: 10.1038/s41571-025-01023-z

Peter Sidaway

引用次数: 0

Sacituzumab tirumotecan improves OS in mTNBC 萨妥珠单抗替鲁莫替康可改善mTNBC的OS

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-04-23 DOI: 10.1038/s41571-025-01022-0

David Killock

引用次数: 0