Nature Reviews Clinical Oncology最新文献_第2页

Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities. 利用CRISPR碱基和引物编辑技术设计的下一代T细胞免疫疗法：挑战和机遇。

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-09-19 DOI: 10.1038/s41571-025-01072-4

Karl Petri,Elvira D'Ippolito,Annette Künkele,Ulrike Köhl,Dirk H Busch,Hermann Einsele,Michael Hudecek

{"title":"Next-generation T cell immunotherapies engineered with CRISPR base and prime editing: challenges and opportunities.","authors":"Karl Petri,Elvira D'Ippolito,Annette Künkele,Ulrike Köhl,Dirk H Busch,Hermann Einsele,Michael Hudecek","doi":"10.1038/s41571-025-01072-4","DOIUrl":"https://doi.org/10.1038/s41571-025-01072-4","url":null,"abstract":"T cells can be reprogrammed with transgenic antigen recognition receptors, including chimeric antigen receptors and T cell receptors, to selectively recognize and kill cancer cells. Such adoptive T cell therapies are effective in patients with certain haematological cancers but challenges persist, including primary and secondary resistance, a lack of efficacy in patients with solid tumours, a narrow range of targetable antigens, and time-consuming and complex manufacturing processes. CRISPR-based genome editing is a potent strategy to enhance cellular immunotherapies. Conventional CRISPR-Cas9 systems are useful for gene editing, transgene knock-in or gene knockout but can result in undesired editing outcomes, including translocations and chromosomal truncations. Base editing and prime editing technologies constitute a new generation of CRISPR platforms and enable highly precise and programmable installation of defined nucleotide variants in primary T cells. Owing to their high precision and versatility, base editing and prime editing systems, hereafter collectively referred to as CRISPR 2.0, are advancing to become the new standard for precision-engineering of cellular immunotherapies. CRISPR 2.0 can be used to augment immune cell function, broaden the spectrum of targetable antigens and facilitate streamlined production of T cell therapies. Notably, CRISPR 2.0 is reaching clinical maturity, with multiple clinical trials of CRISPR 2.0-modified cellular therapies currently ongoing. In this Review, we discuss emerging CRISPR 2.0 technologies and their progress towards clinical translation, highlighting challenges and opportunities, and describe strategies for the use of CRISPR 2.0 to advance cellular immunotherapy for haematological malignancies and solid tumours in the future.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"37 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145089761","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 molecular blueprint of targeted radionuclide therapy 靶向放射性核素治疗的分子蓝图

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-09-09 DOI: 10.1038/s41571-025-01069-z

Irina Primac, Kevin Tabury, Alpaslan Tasdogan, Sarah Baatout, Ken Herrmann

{"title":"The molecular blueprint of targeted radionuclide therapy","authors":"Irina Primac, Kevin Tabury, Alpaslan Tasdogan, Sarah Baatout, Ken Herrmann","doi":"10.1038/s41571-025-01069-z","DOIUrl":"https://doi.org/10.1038/s41571-025-01069-z","url":null,"abstract":"Targeted radionuclide therapy (TRT) is a cutting-edge treatment approach in oncology that combines the molecular precision of targeted agents with the effect of radiotherapy to selectively deliver cytotoxic radiation to cancer cells. Research efforts from the past few decades have led to a diverse molecular landscape of TRT and have provided lessons for further rational development of targeted radiopharmaceuticals and expansion of the clinical applications of this treatment modality. In this Review, we discuss TRT in the context of therapeutic approaches currently available in oncology, describe the broad range of established and emerging targets for TRT including innovative approaches to exploit vulnerabilities presented by the tumour microenvironment, and address the challenges for clinical translation and molecular optimization. By bridging technological innovation and preclinical discoveries with real-world clinical implementation, ongoing research on TRT is seeking to provide effective and safe treatment options for patients across a variety of cancer types and treatment settings. Overall, we emphasize the transformative potential of TRT and highlight how a comprehensive understanding of what constitutes an optimal target can redefine clinical practice, fostering the evolution of TRT as a highly individualized and adaptable therapeutic option that improves outcomes across a broad range of cancer types.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"71 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145017651","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

Non-financial conflicts of interest 非财务利益冲突

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-09-03 DOI: 10.1038/s41571-025-01073-3

Saroj Niraula, Ian F. Tannock

引用次数: 0

Radiomics Quality Score 2.0: towards radiomics readiness levels and clinical translation for personalized medicine 放射组学质量评分2.0：面向个性化医疗的放射组学准备水平和临床翻译

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-09-03 DOI: 10.1038/s41571-025-01067-1

Philippe Lambin, Henry C. Woodruff, Shruti Atul Mali, Xian Zhong, Sheng Kuang, Elizaveta Lavrova, Hamza Khan, Karim Lekadir, Alex Zwanenburg, Joseph Deasy, Maciej Bobowicz, Luis Marti-Bonmati, Andrew Maidment, Michel Dumontier, Paul E. Kinahan, J. Martijn Nobel, Sina Amirrajab, Zohaib Salahuddin

{"title":"Radiomics Quality Score 2.0: towards radiomics readiness levels and clinical translation for personalized medicine","authors":"Philippe Lambin, Henry C. Woodruff, Shruti Atul Mali, Xian Zhong, Sheng Kuang, Elizaveta Lavrova, Hamza Khan, Karim Lekadir, Alex Zwanenburg, Joseph Deasy, Maciej Bobowicz, Luis Marti-Bonmati, Andrew Maidment, Michel Dumontier, Paul E. Kinahan, J. Martijn Nobel, Sina Amirrajab, Zohaib Salahuddin","doi":"10.1038/s41571-025-01067-1","DOIUrl":"https://doi.org/10.1038/s41571-025-01067-1","url":null,"abstract":"Radiomics is a tool for medical imaging analysis that could have a relevant role in precision oncology by offering precise quantitative support for clinical decision-making. The Radiomics Quality Score (RQS) is a tool developed to assess the rigour of radiomics studies that has now been widely adopted by researchers. Although RQS version 1.0 established a benchmark, an updated framework is required to account for evolving knowledge and ensure optimal evaluation of the quality of radiomics studies through the inclusion of fairness, explainability, rigorous quality control and harmonization. In this Review, we introduce the updated RQS 2.0, which maintains the scientific rigour of its predecessor and addresses these contemporary needs, and therefore could potentially accelerate clinical translation. Moreover, we introduce the radiomics readiness levels, inspired by the technology readiness level framework, which are integrated in RQS 2.0 and reflect nine distinct levels of incremental improvement in radiomics research with the ultimate aim of clinical implementation. We also detail anticipated future directions in radiomics, outlining a strategic vision to advance precision oncology, which is the ultimate aim of RQS 2.0.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"16 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144930598","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

Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia 靶向凋亡的BH3模拟物：急性髓性白血病患者的转化治疗

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-09-01 DOI: 10.1038/s41571-025-01068-0

Antonino Glaviano, Ellen Weisberg, Hiu Y. Lam, Donavan J. J. Tan, Andrew J. Innes, Yubin Ge, Catherine E. Lai, Wendy Stock, Christina Glytsou, Linda Smit, Tatsushi Yoshida, Tian Y. Zhang, Vanessa E. Kennedy, B. Douglas Smith, Thomas Mercher, Stéphane de Botton, Patrizia Diana, Marina Konopleva, Michael J. Mauro, James D. Griffin, Courtney D. DiNardo, Alan P. Kumar

{"title":"Apoptosis-targeting BH3 mimetics: transforming treatment for patients with acute myeloid leukaemia","authors":"Antonino Glaviano, Ellen Weisberg, Hiu Y. Lam, Donavan J. J. Tan, Andrew J. Innes, Yubin Ge, Catherine E. Lai, Wendy Stock, Christina Glytsou, Linda Smit, Tatsushi Yoshida, Tian Y. Zhang, Vanessa E. Kennedy, B. Douglas Smith, Thomas Mercher, Stéphane de Botton, Patrizia Diana, Marina Konopleva, Michael J. Mauro, James D. Griffin, Courtney D. DiNardo, Alan P. Kumar","doi":"10.1038/s41571-025-01068-0","DOIUrl":"https://doi.org/10.1038/s41571-025-01068-0","url":null,"abstract":"Acute myeloid leukaemia (AML) remains a challenging haematological malignancy, with most patients developing resistance to standard-of-care (SOC) treatments. This resistance is often attributed to the overexpression of anti-apoptotic BCL-2 family proteins, which regulate the intrinsic apoptotic pathway by inhibiting pro-apoptotic effector proteins such as BAX and BAK. AML cells exploit this imbalance to evade apoptosis and sustain survival, necessitating the development of novel therapeutic strategies. BH3 mimetics are small-molecule inhibitors targeting the pro-survival BCL-2 family proteins and have emerged as promising agents in patients with AML who are unable to receive high-intensity induction chemotherapy. Co-treatment with the BCL-2-specific inhibitor venetoclax and various SOC therapies has been proven effective, with several combinations now approved by the US Food and Drug Administration for adults with AML who are ≥75 years of age and/or are ineligible for intensive induction chemotherapy, on the basis of improved response rates and survival outcomes compared with the previous SOC. In this Review, we highlight the transformative potential of BH3 mimetics in AML therapy, including ongoing studies investigating novel combination regimens and efforts to further refine treatment strategies, with the ultimate goal of improving outcomes for patients with AML.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"1 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144928550","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

Exercise as a new therapeutic modality in oncology: CHALLENGE trial refines survivorship care 运动作为一种新的肿瘤治疗方式：CHALLENGE试验改善了生存护理

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-08-26 DOI: 10.1038/s41571-025-01071-5

Justin Y. Jeon

引用次数: 0

ASTER 70 suggests no clinical benefit from adjuvant chemotherapy in older patients with ER+HER2– breast cancer ASTER 70提示老年ER+HER2-乳腺癌患者辅助化疗无临床获益。

IF 82.2 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-08-18 DOI: 10.1038/s41571-025-01070-6

David Killock

引用次数: 0

Treatment of NSCLC after chemoimmunotherapy - are we making headway? 化疗免疫治疗后非小细胞肺癌的治疗-我们取得进展了吗？

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-08-14 DOI: 10.1038/s41571-025-01061-7

Martin Reck,Nikolaj Frost,Solange Peters,Bernard A Fox,Roberto Ferrara,Rajkumar Savai,Fabrice Barlesi

{"title":"Treatment of NSCLC after chemoimmunotherapy - are we making headway?","authors":"Martin Reck,Nikolaj Frost,Solange Peters,Bernard A Fox,Roberto Ferrara,Rajkumar Savai,Fabrice Barlesi","doi":"10.1038/s41571-025-01061-7","DOIUrl":"https://doi.org/10.1038/s41571-025-01061-7","url":null,"abstract":"The treatment landscape of non-small-cell lung cancer (NSCLC) has evolved considerably with the integration of immune-checkpoint inhibitors (ICIs) into first-line regimens. However, the majority of patients will ultimately have primary resistance or develop secondary resistance, driven by a complex interplay of intrinsic tumour biology and adaptive changes within the tumour microenvironment (TME), which can be further amplified by host-related factors such as dysbiosis and organ-specific conditions. Despite these heterogeneous origins, most mechanisms of resistance to ICIs lead to an immunosuppressive TME as the final common pathway. Consequently, current strategies designed to overcome resistance aim to restore antitumour immunity via antibody-based therapies (including bispecific antibodies, T cell engagers and antibody-drug conjugates), targeted therapies, adoptive cell therapies, therapeutic vaccines or intratumoural immunotherapies. Although substantial progress has been made in identifying potential biomarkers associated with immune resistance, the clinical relevance of many of these observations remains limited. Biomarker-driven studies using adaptive, hypothesis-generating designs might offer a promising path forward by navigating the complexity of resistance and enabling the timely evaluation of novel therapeutic concepts. In this Review, we summarize the latest advances in addressing resistance to ICIs in patients with advanced-stage NSCLC and provide insights into emerging clinical strategies and future research directions.","PeriodicalId":19079,"journal":{"name":"Nature Reviews Clinical Oncology","volume":"24 1","pages":""},"PeriodicalIF":78.8,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144850816","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

Cured but breathless: the growing burden of DIILD in cancer survivors 治愈了却喘不过气来：癌症幸存者的DIILD负担越来越重

IF 82.2 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-08-13 DOI: 10.1038/s41571-025-01064-4

Jing-Xing Li, Wen-Chien Cheng

引用次数: 0

SERENA-6: dynamic ctDNA assessment and the future of precision cancer medicine SERENA-6：动态ctDNA评估和精准癌症医学的未来

IF 78.8 1区医学

Nature Reviews Clinical Oncology Pub Date : 2025-08-07 DOI: 10.1038/s41571-025-01066-2

Arielle J. Medford, Seth A. Wander

引用次数: 0