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Surrogate end points in oncology: aligning drug development incentives and patient needs 肿瘤替代终点:调整药物开发激励和患者需求
IF 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-06-06 DOI: 10.1038/s41571-025-01031-z
Matthew Vogel, Rona Yaeger, David J. Stewart, Vivek Subbiah, Frank S. David
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引用次数: 0
Reply to ‘Surrogate end points in oncology: aligning drug development incentives and patient needs’ 回复“肿瘤替代终点:调整药物开发激励和患者需求”
IF 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-06-06 DOI: 10.1038/s41571-025-01032-y
Vinay Prasad
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引用次数: 0
Novel colorectal cancer screening methods — opportunities and challenges 新型结直肠癌筛查方法——机遇与挑战
IF 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-06-06 DOI: 10.1038/s41571-025-01037-7
Melina A. McCabe, Anthony J. Mauro, Robert E. Schoen
Globally, colorectal cancer (CRC) is the second leading cause of cancer death and the third most common incident cancer. CRC begins as adenomatous or serrated polyps, and in particular as advanced precursor lesions (APLs), which have the potential to progress into invasive cancers. Screening for CRC facilitates early detection and can identify cancers more amenable to cure, and can also detect and remove precursor lesions, thus also preventing CRC. Colonoscopy is the mainstay of screening in the USA and has the distinct advantage of enabling both detection and removal of precursors lesions. However, colonoscopy is burdensome, expensive and invasive, and often has negative findings. Non-invasive tests, such as testing stool samples for biomarkers of risk, have the potential to identify individuals who are more likely to benefit from colonoscopy. From a public health perspective, improving compliance with screening remains a priority. Technological innovations, including the emergence of new markers to improve stool testing and the development of blood tests that examine cell-free DNA have the potential to improve screening uptake and effectiveness. The trade-off between uptake of screening testing, detection of cancer and important precursor lesions such as APLs, and costs make for a complex calculus. In this Review, we describe the current state of CRC screening and evaluate the risks and benefits of new developments in screening. Despite being the second most lethal and the third most prevalent form of cancer, most cases of colorectal cancer (CRC) can be either detected at an early stage or prevented using screening colonoscopy with removal of precursor lesions. Nonetheless, universal colonoscopy is expensive and time consuming, and can be unpopular. Other less-invasive screening tests involving either faeces or more recently blood samples have the potential to improve overall CRC screening uptake and are an active area of research and development. In this Review, the authors describe the clinical utility of novel CRC screening methods such as multitarget stool DNA tests and blood cell-free DNA tests, including both the challenges and opportunities arising from their implementation.
在全球范围内,结直肠癌(CRC)是癌症死亡的第二大原因,也是第三大常见癌症。结直肠癌开始为腺瘤状或锯齿状息肉,特别是晚期前体病变(apl),有可能发展为侵袭性癌症。筛查结直肠癌有助于早期发现和识别更容易治愈的癌症,也可以发现和切除前驱病变,从而预防结直肠癌。结肠镜检查是筛查在美国的中流砥柱,具有明显的优势,使检测和去除前体病变。然而,结肠镜检查是繁重的,昂贵的和侵入性的,往往是阴性的结果。非侵入性检查,如检测粪便样本的生物风险标志物,有可能识别出更有可能从结肠镜检查中受益的个体。从公共卫生的角度来看,改善对筛查的遵守情况仍然是一个优先事项。技术创新,包括改进粪便检测的新标记的出现和检查无细胞DNA的血液检测的发展,有可能提高筛查的吸收和有效性。在接受筛查测试、检测癌症和重要的前驱病变(如api)与成本之间进行权衡,是一个复杂的计算。在这篇综述中,我们描述了CRC筛查的现状,并评估了筛查新进展的风险和益处。
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引用次数: 0
Empowering oncologists: a practical approach to overcoming barriers to clinical trial enrolment 授权肿瘤学家:克服临床试验登记障碍的实用方法
IF 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-06-03 DOI: 10.1038/s41571-025-01038-6
Changchuan Jiang, Ryan D. Nipp, Tian Zhang
Oncologists have crucial yet under-studied and often under-supported roles in promoting clinical trial referral and enrolment. Herein, we advocate for a systemic shift that acknowledges the operational barriers oncologists face and enhances structural support through streamlined workflows and behavioural science-informed strategies to facilitate their participation in clinical trial enrolment.
肿瘤学家在促进临床试验转诊和招募方面发挥着至关重要的作用,但研究不足,而且往往得不到支持。在此,我们提倡系统性转变,承认肿瘤学家面临的操作障碍,并通过简化的工作流程和行为科学知情策略加强结构支持,以促进他们参与临床试验注册。
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引用次数: 0
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 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-05-29 DOI: 10.1038/s41571-025-01034-w
Ghulam Rehman Mohyuddin, Aaron M. Goodman
In pivotal trials testing daratumumab in patients with transplant-ineligible newly diagnosed multiple myeloma, inadequate crossover provisions have not only compromised the interpretation of survival data but also left fundamental questions about optimal treatment sequencing unanswered. Herein, we address the ethical implications of trial designs that fail to guarantee access to effective post-progression therapy for patients in the control arm, particularly in studies across regions in which standard-of-care treatment varies dramatically.
在对新诊断的不适合移植的多发性骨髓瘤患者测试daratumumab的关键试验中,不充分的交叉规定不仅损害了生存数据的解释,而且还留下了关于最佳治疗序列的基本问题。在此,我们讨论了不能保证对照组患者获得有效进展后治疗的试验设计的伦理意义,特别是在标准治疗差异很大的地区的研究中。
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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 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-05-29 DOI: 10.1038/s41571-025-01039-5
Peter Sidaway
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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 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-05-23 DOI: 10.1038/s41571-025-01036-8
Diana Romero
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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 82.2 1区 医学 Q1 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
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. Despite advances in drug development, some patients with non-small-cell lung cancer (NSCLC) have suboptimal responses to treatment. The authors of this Review provide an overview of the complexity of the tumour microenvironment in NSCLC, including the influence of patient-related factors, such as ageing, sex and health disparities, on the cancer–TME crosstalk, and discuss how various therapeutic strategies interact with and are influenced by the TME in NSCLC.
在靶向药物和免疫疗法发展的推动下,非小细胞肺癌(NSCLC)的治疗前景正在迅速发展。尽管取得了这一进展,但一些患者对治疗的反应不佳,这突出了对新治疗策略的需求。在过去的十年中,肿瘤微环境(tumor microenvironment, TME)在NSCLC进展、转移传播和治疗反应中的重要作用越来越明显。了解TME的复杂性及其与NSCLC的相互作用可以推动改进当前的治疗方式,克服耐药性并开发新的治疗方法,最终改善患者的预后。在这篇综述中,我们提供了NSCLC TME的全面观点,研究了其组成部分,并强调了以肿瘤巢内和周围的空间壁龛为特征的不同原型,这些空间壁龛形成了复杂的社区。接下来,我们将探讨这些成分之间的相互作用,重点关注炎症和免疫抑制如何影响NSCLC TME的动态。我们还讨论了与患者相关的因素,如年龄、性别和健康差异,对NSCLC-TME相声的新影响。最后,我们讨论了各种治疗策略如何与非小细胞肺癌的TME相互作用并受其影响。总之,我们强调这些因素的相互联系,以及它们如何影响治疗结果和肿瘤进展。
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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 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-05-14 DOI: 10.1038/s41571-025-01026-w
Ya-Qi Gao, Yong-Jie Tan, Jing-Yuan Fang
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. The composition of the gut microbiota has been implicated as a key determinant of not only the clinical efficacy but also the immune-related adverse effects (irAEs) of immune checkpoint inhibitors. This Review describes the reported correlations between alterations in the gut microbiota and irAEs, as well as their potential underlying mechanisms and possible predictive utility. Gut microbial interventions that might serve as new strategies for the management of irAEs are also discussed.
免疫检查点抑制剂(ICIs)是癌症治疗领域的重大突破;它们的使用改善了各种肿瘤类型的治疗效果。然而,ICIs可引起多种免疫相关不良事件(irAEs),这对这些治疗的有效性和安全性提出了相当大的挑战。肠道微生物群已被证明在调节肿瘤免疫微环境中起着至关重要的作用,从而影响ICIs的有效性。越来越多的证据表明,肠道微生物群组成和功能的改变也与irae风险增加有关,特别是ici诱导的结肠炎。事实上,肠道菌群的这些变化可能导致irae的发病机制。在这篇综述中,我们首先总结了目前irAEs所面临的临床挑战。然后,我们将重点放在已报道的肠道微生物群变化与irAEs之间的相关性,特别是ici诱导的结肠炎,并假设这些微生物变化影响irAEs发生的机制。最后,我们强调了肠道微生物变化作为预测irAEs的生物标志物的潜在价值,并讨论了可能作为irAEs管理新策略的肠道微生物干预措施,包括粪便微生物群移植,益生菌,益生元和/或后益生菌补充剂以及饮食调节。
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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 82.2 1区 医学 Q1 ONCOLOGY Pub Date : 2025-05-14 DOI: 10.1038/s41571-025-01020-2
Thomas Kisby, Gerben R. Borst, David J. Coope, Kostas Kostarelos
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. Patients with resectable glioblastoma undergo upfront surgery followed by adjuvant radiotherapy plus chemotherapy. This approach implies a period of approximately 4–6 weeks between surgery and the start of adjuvant therapy in which the patient receives no active treatment. In this Perspective, the authors describe the potential of local therapies targeting the tumour resection margin that can be administered during this time window, including biological feasibility, the potential role of nanomedicines and various technical and regulatory challenges that will need to be addressed before clinical implementation becomes feasible.
手术切除是可切除胶质母细胞瘤患者的第一阶段治疗,随后是辅助放疗和全身单药化疗的联合治疗,通常在手术后4-6周开始。这种延迟造成了一个间隔,在此期间,残留在切除边缘的肿瘤细胞可以不受抑制地增殖和进一步侵袭,甚至在手术后立即发生,从而限制了辅助治疗的有效性。认识到术后切除边缘和边缘周围区域是重要的解剖学临床目标,需要重新思考当前的策略,可以激发局部,术中入路的机会,同时也产生了创新治疗模式的新景观。在这个观点中,我们讨论了发展局部区域治疗策略的机遇和挑战,以靶向胶质母细胞瘤切除边缘,以及纳米技术在这个临床变革环境中提供的新兴机会。我们还讨论了如何克服临床翻译的持续障碍,为这种先进技术的更广泛可接受性提供潜在的途径。
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Nature Reviews Clinical Oncology
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