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CABINET presents cabozantinib as a new treatment option for NETs CABINET 提出卡博替尼是治疗 NET 的新方案
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-24 DOI: 10.1038/s41571-024-00949-0
David Killock
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引用次数: 0
Neoadjuvant immunotherapy for dMMR and pMMR colorectal cancers: therapeutic strategies and putative biomarkers of response 针对dMMR和pMMR结直肠癌的新辅助免疫疗法:治疗策略和反应的假定生物标志物
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-24 DOI: 10.1038/s41571-024-00943-6
Christopher J. M. Williams, Allyson M. Peddle, Pashtoon M. Kasi, Jenny F. Seligmann, Campbell S. Roxburgh, Gary W. Middleton, Sabine Tejpar
Approximately 15% of locally advanced colorectal cancers (CRC) have DNA mismatch repair deficiency (dMMR), resulting in high microsatellite instability and a high tumour mutational burden. These cancers are frequently sensitive to therapy with immune-checkpoint inhibitors (ICIs) in the metastatic setting. This sensitivity seems to be even more pronounced in locally advanced disease, and organ preservation has become a realistic aim in ongoing clinical trials involving patients with dMMR rectal cancer. By contrast, metastatic CRCs with proficient DNA mismatch repair (pMMR) are generally resistant to ICIs, although a proportion of locally advanced pMMR tumours seem to have a high degree of sensitivity to ICIs. In this Review, we describe the current and emerging clinical evidence supporting the use of neoadjuvant ICIs in patients with dMMR and pMMR CRC, and the potential advantages (based on a biological rationale) of such an approach. We discuss how neoadjuvant ‘window-of-opportunity’ trials are being leveraged to progress biomarker discovery and we provide an overview of potential predictive biomarkers of response to ICIs, exploring the challenges faced when evaluating such biomarkers in biopsy-derived samples. Lastly, we describe how these discoveries might be used to drive a rational approach to trialling novel immunotherapeutic strategies in patients with pMMR CRC, with the ultimate aim of disease eradication and the generation of long-term immunosurveillance. Locally advanced colorectal cancers (CRCs) with DNA mismatch repair deficiency have sensitivity to immune-checkpoint inhibitors, and evidence suggests that this is also the case for a proportion of proficient DNA mismatch repair CRCs. The authors of this Review describe the emerging clinical evidence supporting the use of neoadjuvant immune-checkpoint inhibitors in patients with CRC and discuss how clinical research (including on biomarkers) can be used to improve clinical outcomes in this setting.
大约 15%的局部晚期结直肠癌(CRC)存在 DNA 错配修复缺陷(dMMR),导致微卫星高度不稳定和高肿瘤突变负荷。这些癌症往往对转移性免疫检查点抑制剂(ICIs)治疗敏感。这种敏感性在局部晚期疾病中似乎更为明显,在目前涉及 dMMR 直肠癌患者的临床试验中,保留器官已成为一个现实的目标。相比之下,具有熟练 DNA 错配修复(pMMR)能力的转移性 CRC 通常对 ICIs 具有抗药性,尽管一部分局部晚期 pMMR 肿瘤似乎对 ICIs 具有高度敏感性。在本综述中,我们将介绍支持在 dMMR 和 pMMR CRC 患者中使用新辅助 ICIs 的现有和新出现的临床证据,以及这种方法的潜在优势(基于生物学原理)。我们讨论了如何利用新辅助 "机会之窗 "试验来推动生物标志物的发现,并概述了对 ICIs 反应的潜在预测性生物标志物,探讨了在活检样本中评估此类生物标志物所面临的挑战。最后,我们介绍了如何利用这些发现来推动在 pMMR CRC 患者中试用新型免疫治疗策略的合理方法,最终达到根除疾病和产生长期免疫监视的目的。
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引用次数: 0
A new standard of care for leiomyosarcoma 治疗子宫肌瘤的新标准
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-19 DOI: 10.1038/s41571-024-00947-2
Peter Sidaway
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引用次数: 0
Dual HER2 inhibition: mechanisms of synergy, patient selection, and resistance 双重 HER2 抑制:协同作用机制、患者选择和耐药性
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-13 DOI: 10.1038/s41571-024-00939-2
Adrienne G. Waks, Olga Martínez-Sáez, Paolo Tarantino, Fara Braso-Maristany, Tomás Pascual, Javier Cortés, Sara M. Tolaney, Aleix Prat
HER2-targeted therapies for patients with HER2+ breast cancer are rapidly evolving, offering a range of more complex and personalized treatment options. Currently, an array of anti-HER2 monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates are administered, sometimes alongside chemotherapy or endocrine therapy, both in curative and palliative contexts. However, the heterogeneous nature of HER2+ breast cancer demands a deeper understanding of disease biology and its role in responsiveness to novel HER2-targeted agents, as well as non-HER2-targeted therapies, in order to optimize patient outcomes. In this Review, we revisit the mechanisms of action of HER2-targeted agents, examine the evidence supporting the use of dual HER2 blockade in patients with HER2-amplified tumours, and explore the role of biomarkers in guiding future treatment strategies. We also discuss potential implications for the future treatment of patients with HER2+ breast cancer. Patients with HER2+ breast cancer often respond to trastuzumab, although acquired resistance is common and can involve a range of mechanisms. reflecting the highly heterogeneous biology of this breast cancer subtype. In this Review, the authors describe the role of dual HER2 blockade, involving the co-administration of two HER2-targeted therapies (including monoclonal antibodies, tyrosine kinase inhibitors and antibody–drug conjugates) in patients with HER2+ breast cancer.
针对 HER2+ 乳腺癌患者的 HER2 靶向疗法发展迅速,提供了一系列更复杂、更个性化的治疗方案。目前,一系列抗 HER2 单克隆抗体、酪氨酸激酶抑制剂和抗体药物共轭物被用于治疗和姑息治疗,有时与化疗或内分泌治疗同时使用。然而,HER2+乳腺癌的异质性要求我们更深入地了解疾病生物学及其在新型HER2靶向药物和非HER2靶向疗法中的作用,以优化患者的治疗效果。在本综述中,我们将重新审视 HER2 靶向药物的作用机制,研究支持在 HER2 扩增肿瘤患者中使用双重 HER2 阻断的证据,并探讨生物标志物在指导未来治疗策略中的作用。我们还讨论了对未来治疗 HER2+ 乳腺癌患者的潜在影响。
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引用次数: 0
Vorasidenib: a new hope or a false promise for patients with low-grade glioma? Vorasidenib:低级别胶质瘤患者的新希望还是虚假承诺?
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-12 DOI: 10.1038/s41571-024-00944-5
Stanislav Lazarev, Kunal K. Sindhu
Despite recent FDA approval, the clinical utility of vorasidenib in the treatment of IDH-mutant low-grade gliomas remains unclear. Herein, we critique the pivotal trial of vorasidenib, and highlight the questionable choice of control intervention and end points, ethical concerns, as well as the uncertain efficacy observed, and argue that the approval might be premature given the high cost of this drug and lack of clear benefit over standard treatments.
尽管最近获得了美国食品药品管理局的批准,但vorasidenib治疗IDH突变低级别胶质瘤的临床效用仍不明确。在此,我们对vorasidenib的关键性试验进行了评论,并强调了对照干预和终点选择的问题、伦理问题以及观察到的不确定疗效,并认为鉴于该药物的高昂成本以及与标准疗法相比缺乏明显疗效,批准该药物的时机可能还不成熟。
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引用次数: 0
New clinical trials in CUP and a novel paradigm in cancer classification CUP 的新临床试验和癌症分类的新范例
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-11 DOI: 10.1038/s41571-024-00942-7
Elie Rassy, Fabrice André
Precision oncology has reached a milestone as data from two trials in which molecular profiling guided both site-specific and tumour-agnostic therapies indicate improved survival outcomes in patients with cancer of unknown primary. These findings can also be extrapolated and support the use of tissue-agnostic approaches in general, and also suggest that the tissue of origin might have a role in the agnostic classification of cancers and their response to treatment.
精准肿瘤学已经达到了一个里程碑,在两项试验中,分子图谱指导了特定部位和肿瘤诊断疗法,试验数据表明,原发灶不明癌症患者的生存率有所提高。这些研究结果还可以推而广之,支持在一般情况下使用组织诊断方法,并表明原发组织可能在癌症的不可知论分类及其对治疗的反应中发挥作用。
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引用次数: 0
The age of foundation models 基础模型时代
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-05 DOI: 10.1038/s41571-024-00941-8
Jana Lipkova, Jakob Nikolas Kather
The development of clinically relevant artificial intelligence (AI) models has traditionally required access to extensive labelled datasets, which inevitably centre AI advances around large centres and private corporations. Data availability has also dictated the development of AI applications: most studies focus on common cancer types, and leave rare diseases behind. However, this paradigm is changing with the advent of foundation models, which enable the training of more powerful and robust AI systems using much smaller datasets.
传统上,开发临床相关的人工智能(AI)模型需要获取大量标记数据集,这就不可避免地使人工智能的发展集中在大型中心和私营企业周围。数据的可用性也决定了人工智能应用的发展:大多数研究都集中在常见癌症类型上,而将罕见疾病抛在脑后。然而,随着基础模型的出现,这种模式正在发生变化,它可以使用小得多的数据集来训练更强大、更稳健的人工智能系统。
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引用次数: 0
Immunotherapy for ovarian cancer: towards a tailored immunophenotype-based approach 卵巢癌免疫疗法:迈向基于免疫表型的定制方法
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-09-04 DOI: 10.1038/s41571-024-00937-4
Eleonora Ghisoni, Matteo Morotti, Apostolos Sarivalasis, Alizée J. Grimm, Lana Kandalaft, Denarda Dangaj Laniti, George Coukos
Despite documented evidence that ovarian cancer cells express immune-checkpoint molecules, such as PD-1 and PD-L1, and of a positive correlation between the presence of tumour-infiltrating lymphocytes and favourable overall survival outcomes in patients with this tumour type, the results of trials testing immune-checkpoint inhibitors (ICIs) in these patients thus far have been disappointing. The lack of response to ICIs can be attributed to tumour heterogeneity as well as inherent or acquired resistance associated with the tumour microenvironment (TME). Understanding tumour immunobiology, discovering biomarkers for patient selection and establishing optimal treatment combinations remains the hope but also a key challenge for the future application of immunotherapy in ovarian cancer. In this Review, we summarize results from trials testing ICIs in patients with ovarian cancer. We propose the implementation of a systematic CD8+ T cell-based immunophenotypic classification of this malignancy, followed by discussions of the preclinical data providing the basis to treat such immunophenotypes with combination immunotherapies. We posit that the integration of an accurate TME immunophenotype characterization with genetic data can enable the design of tailored therapeutic approaches and improve patient recruitment in clinical trials. Lastly, we propose a roadmap incorporating tissue-based profiling to guide future trials testing adoptive cell therapy approaches and assess novel immunotherapy combinations while promoting collaborative research. Although ovarian cancer is considered an immunoreactive disease, moderate to no efficacy has been shown in the trials testing immune-checkpoint inhibitors in these patients performed thus far. The authors of this Review summarize these results and propose a systematic classification of ovarian cancer based on CD8+ T cell immunophenotypes that, integrated with genetic data, can enable the design of tailored therapeutic approaches, including adoptive cell therapy and novel immunotherapy combinations.
尽管有文献证明卵巢癌细胞表达免疫检查点分子(如 PD-1 和 PD-L1),而且肿瘤浸润淋巴细胞的存在与该肿瘤类型患者良好的总体生存结果之间存在正相关,但迄今为止在这些患者中测试免疫检查点抑制剂(ICIs)的试验结果却令人失望。对 ICIs 缺乏反应可归因于肿瘤异质性以及与肿瘤微环境(TME)相关的固有或获得性抵抗。了解肿瘤免疫生物学、发现用于患者选择的生物标志物以及建立最佳治疗组合仍然是卵巢癌免疫疗法未来应用的希望所在,但也是关键挑战。在本综述中,我们总结了在卵巢癌患者中测试 ICIs 的试验结果。我们建议对这种恶性肿瘤进行系统的基于 CD8+ T 细胞的免疫分型分类,然后讨论临床前数据,为用联合免疫疗法治疗这种免疫分型提供依据。我们认为,将准确的 TME 免疫表型特征与基因数据相结合,可以设计出量身定制的治疗方法,并改善临床试验中的患者招募情况。最后,我们提出了一个路线图,将基于组织的特征分析纳入其中,以指导未来测试收养细胞疗法方法的试验,并评估新型免疫疗法组合,同时促进合作研究。
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引用次数: 0
Redefining priorities: a call for patient-centred cancer care and research 重新确定优先事项:呼吁开展以患者为中心的癌症护理和研究
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-08-29 DOI: 10.1038/s41571-024-00940-9
Carolyn Taylor
My close experience with cancer and interactions with other patients, caregivers and health-care providers have shaped my belief that patients must be at the centre of research and care. In this Comment, I advocate for a redirection of research efforts in order to measure patient-centred outcomes and address health disparities.
我与癌症的亲密接触以及与其他患者、护理人员和医疗服务提供者的交流,使我坚信患者必须成为研究和护理的中心。在这篇评论中,我主张重新调整研究方向,以衡量以患者为中心的结果并解决健康差异问题。
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引用次数: 0
Translating biological insights into improved management of endometrial cancer 将生物学知识转化为更好的子宫内膜癌治疗方法
IF 81.1 1区 医学 Q1 ONCOLOGY Pub Date : 2024-08-28 DOI: 10.1038/s41571-024-00934-7
Jeffrey A. How, Amir A. Jazaeri, Shannon N. Westin, Barrett C. Lawson, Ann H. Klopp, Pamela T. Soliman, Karen H. Lu
Endometrial cancer (EC) is the most common gynaecological cancer among women in high-income countries, with both incidence and mortality continuing to increase. The complexity of the management of patients with EC has evolved with greater comprehension of the underlying biology and heterogeneity of this disease. With a growing number of novel therapeutic agents available, emerging treatment regimens seem to have the potential to help to address the concerning trends in EC-related mortality. In this Review, we describe the epidemiology, histopathology and molecular classification of EC as well as the role of the new (2023) International Federation of Gynecologists and Obstetricians (FIGO) staging model. Furthermore, we provide an overview of disease management in the first-line and recurrent disease settings. With increasing use of molecular profiling and updates in treatment paradigms, we also summarize new developments in this rapidly changing treatment landscape. Endometrial cancer is the commonest gynaecological cancer in economically developed countries, and both the incidence and mortality continue to increase. This increasing prevalence highlights the need for novel treatment approaches that will improve patient outcomes. In this Review, the authors describe the epidemiology and standard-of-care treatment approaches for patients with endometrial cancer, as well as highlighting the importance of understanding tumour biology and incorporating this knowledge into better-informed treatment strategies for specific subgroups of patients.
子宫内膜癌(EC)是高收入国家妇女中最常见的妇科癌症,其发病率和死亡率都在持续上升。随着人们对这种疾病的生物学基础和异质性有了更深入的了解,子宫内膜癌患者的治疗也变得越来越复杂。随着越来越多的新型治疗药物问世,新出现的治疗方案似乎有可能帮助解决EC相关死亡率的令人担忧的趋势。在这篇综述中,我们介绍了EC的流行病学、组织病理学和分子分类,以及新的(2023年)国际妇产科联盟(FIGO)分期模型的作用。此外,我们还概述了一线和复发性疾病的疾病管理。随着分子图谱分析的日益广泛应用和治疗范例的不断更新,我们还总结了这一快速变化的治疗领域的新进展。
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引用次数: 0
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Nature Reviews Clinical Oncology
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