Cancer treatment reviews最新文献_第5页

Mismatch repair deficiency/microsatellite instability (dMMR/MSI-H) in rectal cancer patients treated with standard neoadjuvant therapy: a systematic review and meta-analysis 标准新辅助治疗在直肠癌患者中的错配修复缺陷/微卫星不稳定性（dMMR/MSI-H）：一项系统回顾和荟萃分析

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-10-17 DOI: 10.1016/j.ctrv.2025.103039

Gianluca Ricco , Chiara Gallio , Nada Benhima , Irene Assaf , Jean-Luc Van Laethem , Francesco Sclafani

Mismatch repair deficiency or microsatellite instability (dMMR/MSI-H) is an established biomarker in early-stage colon cancer and metastatic colorectal cancer. However, its prognostic significance in early-stage rectal cancer patients treated with neoadjuvant therapy remains uncertain. We aimed to fill this gap by conducting a systematic review and meta-analysis of the available evidence. PubMed, Embase and Scopus were systematically searched from inception to 11/03/2025 for studies comparing the outcome of dMMR/MSI-H and MMR proficient/microsatellite stable (pMMR/MSS) rectal cancer patients treated with neoadjuvant therapy. Studies of immune checkpoint inhibitors were excluded. Data on pathologic complete response (pCR), pathologic tumor regression grade (pTRG), disease-free survival (DFS) and overall survival (OS) were extracted. Pooled odds ratios (ORs) and hazard ratios (HRs) with their 95 % confidence interval (95 % CI) were calculated using a random effects model. After screening 705 records, 26 retrospective studies were included, the majority of patients being treated with long-course chemoradiotherapy. There was a significant association between dMMR/MSI-H status and pCR (OR 1.50 [95 % CI: 1.04–2.14]; p = 0.03), while no association was found for pTRG (OR 0.77 [95 % CI: 0.44–1.34]; p = 0.326), DFS (HR 1.00 [95 % CI: 0.50–2.01]; p = 0.998) and OS (HR 1.42 [95 % CI: 1.00–2.01]; p = 0.051). Despite the limited data, subgroup analyses did not appear to reveal any significant difference by type of neoadjuvant treatment. In conclusion, patients with dMMR/MSI-H rectal cancer treated with standard neoadjuvant therapy are more likely to achieve a pCR than those with pMMR/MSS tumors.

错配修复缺陷或微卫星不稳定性（dMMR/MSI-H）是早期结肠癌和转移性结直肠癌的既定生物标志物。然而，其在早期直肠癌患者新辅助治疗中的预后意义尚不确定。我们旨在通过对现有证据进行系统回顾和荟萃分析来填补这一空白。系统检索PubMed， Embase和Scopus，从成立到2025年3月11日，比较dMMR/MSI-H和MMR精通/微卫星稳定（pMMR/MSS）直肠癌患者接受新辅助治疗的结果。排除了免疫检查点抑制剂的研究。提取病理完全缓解（pCR）、病理肿瘤消退分级（pTRG）、无病生存期（DFS）和总生存期（OS）数据。采用随机效应模型计算合并优势比（ORs）和风险比（hr）及其95%置信区间（95% CI）。在筛选了705份记录后，纳入了26项回顾性研究，大多数患者接受了长疗程的放化疗。dMMR/MSI-H状态与pCR （OR 1.50 [95% CI: 1.04-2.14]; p = 0.03）有显著相关性，而pTRG （OR 0.77 [95% CI: 0.44-1.34]; p = 0.326）、DFS （HR 1.00 [95% CI: 0.50-2.01]; p = 0.998）和OS （HR 1.42 [95% CI: 1.00-2.01]; p = 0.051）无相关性。尽管数据有限，亚组分析似乎没有显示新辅助治疗类型的任何显著差异。总之，采用标准新辅助治疗的dMMR/MSI-H直肠癌患者比pMMR/MSS肿瘤患者更有可能实现pCR。

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引用次数: 0

Precision oncology in gastric cancer: Shaping the future of personalized treatment 胃癌精准肿瘤学：塑造个性化治疗的未来

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-10-16 DOI: 10.1016/j.ctrv.2025.103038

Cristina Migliore , Elisabetta Fenocchio , Silvia Giordano , Simona Corso

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide, and is associated with a very poor prognosis, largely due to its aggressive nature and, typically, late-stage diagnosis. Molecular classifications proposed one decade ago have provided valuable insights into the disease’s heterogeneity and paved the way for clinical trials of tailored treatments. However, most of these trials have failed, often due to inadequate patient selection, lack of reliable biomarkers of response/resistance, or for the high level of inter- and intra-tumor heterogeneity characterizing this disease.

This Review provides an in-depth and up-to-date overview of the preclinical models of GC developed in recent years. These include patient-derived xenografts (PDXs), organoids (PDOs), and genetically engineered mouse models (GEMMs), which are valuable tools for elucidating disease mechanisms and for preclinical drug testing. We also highlight emerging molecular targets and innovative therapeutic strategies—such as immunotherapies, antibody-drug conjugates, and synthetic lethality approaches—designed to overcome the mechanisms of resistance that limit current treatment efficacy.

Together, these improvements offer renewed hope for more effective and durable treatment options in GC, ultimately aiming to improve patient outcomes through a more tailored approach.

胃癌（GC）是全球癌症相关死亡的第三大原因，其预后非常差，主要是由于其侵袭性和通常的晚期诊断。十年前提出的分子分类为该病的异质性提供了有价值的见解，并为定制治疗的临床试验铺平了道路。然而，大多数这些试验都失败了，通常是由于患者选择不足，缺乏可靠的反应/耐药生物标志物，或者肿瘤间和肿瘤内的高水平异质性。这篇综述提供了近年来GC临床前模型的深入和最新综述。这些包括患者来源的异种移植物（PDXs），类器官（PDOs）和基因工程小鼠模型（GEMMs），它们是阐明疾病机制和临床前药物测试的宝贵工具。我们还强调了新兴的分子靶点和创新的治疗策略，如免疫疗法、抗体-药物偶联物和合成致死性方法，旨在克服限制当前治疗效果的耐药机制。总之，这些改进为更有效和持久的胃癌治疗方案带来了新的希望，最终旨在通过更有针对性的方法改善患者的预后。

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引用次数: 0

Assessing lung function in women treated for breast cancer with radiotherapy. A comprehensive systematic review and meta-analysis 评估接受放疗的乳腺癌患者的肺功能。一个全面的系统回顾和荟萃分析

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-10-13 DOI: 10.1016/j.ctrv.2025.103027

N. Daga-Guijarro , N.S. Diciolla , M.J. Yuste-Sánchez

Background

Radiotherapy is associated with pulmonary fibrosis in 5–15% of cases, potentially impacting lung function and thus the quality of life of patients with breast cancer. This study aimed to assess short, middle, and long-term effects of radiotherapy on lung function in women treated for breast cancer.

Materials and methods

A thorough literature search of databases (Medline, Web of Science, Scopus, and CENTRAL) up to October 2024 was conducted. Included were observational, experimental, and quasi-experimental studies assessing radiotherapy effects on lung function in women treated for breast cancer. A meta-analysis summarised findings, and risk of bias (Cochrane ROBINS-E) and quality of evidence (GRADE framework) were assessed.

Results

Twenty-two studies totalled 1042 women, of median age 51 years [range 44–56]. Radiotherapy administered conventionally (46–58 Gy, 1.8–2.2 Gy/fraction, 23–28 sessions, 5 days/week, 5 weeks) or hypo-fractionated (40–43.2 Gy, 2.7–2.8 Gy/fraction, 15–16 sessions, 5 days/week, 3 weeks), resulted in significant declines in FEV₁%predicted, FVC%predicted, and DLCO%predicted at one-, three-, six-, and 12-months post-radiotherapy. Clinically relevant reductions (≥5%) were noted for FEV₁%predicted at one and 12 months (MD[95 %CI) = −7.94[−13.94; −1.93], −5.10[−8.81; −1.39], respectively), FVC%predicted at one, six, and 12 months (−5.98[−11.78; −0.17], −5.90[−9.01; −2.79], −5.58[−9.32;−1.83], respectively), and DLCO%predicted at one, three, and 12 months (−8.00[−15.66; −0.34], −5.51[−7.91; −3.11], −6.76 [−10.27; −3.25], respectively). Risk of bias was low in 64 %, moderate in 14 %, and high in 23 % of studies. GRADE assessment indicated moderate level of evidence.

Conclusions

Radiotherapy may affect lung function in women treated for breast cancer, especially in the absence of lung-sparing techniques, resulting in declines persisting up to 12 months post-radiation. However, heterogeneity in patient characteristics and treatment protocols among studies warrants cautious interpretation of these findings. This highlights the need for enhanced monitoring and supportive pharmacological and non-pharmacological interventions in this patient group.

背景：放射治疗在5-15%的病例中与肺纤维化相关，可能影响肺功能，从而影响乳腺癌患者的生活质量。本研究旨在评估放疗对乳腺癌患者肺功能的短期、中期和长期影响。材料与方法对截至2024年10月的Medline、Web of Science、Scopus、CENTRAL数据库进行了全面的文献检索。包括观察性、实验性和准实验性研究，评估放疗对乳腺癌治疗妇女肺功能的影响。荟萃分析总结了研究结果，并评估了偏倚风险（Cochrane ROBINS-E）和证据质量（GRADE框架）。结果22项研究共纳入1042名女性，中位年龄51岁[范围44 ~ 56岁]。常规放疗（46-58 Gy, 1.8-2.2 Gy/分次，23-28次，5天/周，5周）或次分割放疗（40-43.2 Gy, 2.7-2.8 Gy/分次，15-16次，5天/周，3周），在放疗后1个月、3个月、6个月和12个月，预测fev1%、预测FVC%和预测DLCO%显著下降。1个月和12个月预测fev1 %的临床相关降低（≥5%）(MD[95% CI] = - 7.94[- 13.94；(−−1.93,5.10−8.81;预测1、6、12个月FVC%（分别为- 5.98[- 11.78;- 0.17]、- 5.90[- 9.01;- 2.79]、- 5.58[- 9.32;- 1.83]），1、3、12个月DLCO%（分别为- 8.00[- 15.66;- 0.34]、- 5.51[- 7.91;- 3.11]、- 6.76[- 10.27;- 3.25]）。64%的研究偏倚风险为低，14%为中等，23%为高。GRADE评估显示证据水平中等。结论放疗可能影响乳腺癌患者的肺功能，特别是在没有肺保留技术的情况下，导致放疗后12个月的肺功能下降。然而，研究中患者特征和治疗方案的异质性需要对这些发现进行谨慎的解释。这突出了对该患者群体加强监测和支持性药物和非药物干预的必要性。

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引用次数: 0

Emerging mechanisms of triple-negative breast cancer radioresistance: Interplay between cancer cell mechanisms and the tumor immune microenvironment 三阴性乳腺癌放射耐药的新机制：癌细胞机制与肿瘤免疫微环境之间的相互作用

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-28 DOI: 10.1016/j.ctrv.2025.103026

Ana Canha-Borges , Bárbara Nunes , Sofia Torres Quintas , Joana Paredes , Lydia Meziani , Michele Mondini , Maria José Oliveira , Eric Deutsch , Flávia Castro

Breast cancer is the most common and deadliest cancer in women worldwide. Among the distinct subtypes, triple negative breast cancer (TNBC) stands out as the most aggressive one, showing high resistance to treatments, including chemotherapy, radiotherapy, and immunotherapy.

Radiotherapy remains a standard treatment for TNBC, offering significant benefits in reducing local relapse. However, resistance to radiotherapy remains a major challenge, limiting its effectiveness and narrowing treatment options. Radioresistance in TNBC is driven by both tumor cell-intrinsic mechanisms and tumor immune microenvironment (TIME)-related processes. Intrinsically, TNBC cells employ strategies such as enhanced DNA damage repair mechanisms, tumor hypoxia adaptation, activation of survival pathways, and the contribution of cancer stem cells and extracellular vesicles. Extrinsically, the TIME can further fuel resistance by recruiting immunosuppressive cells (myeloid-derived suppressor cells, macrophages, neutrophils and regulatory T cells) and by releasing factors that impair the antitumor immune response mediated by T cells and natural killer cells.

This review explores the dual contribution of cancer cell-specific mechanisms and TIME dynamics in TNBC radioresistance. We further discuss the paradoxical role of the immune system in radioresponse, highlighting emerging combination therapies, and address the challenges of translating these strategies into clinical applications. Ongoing clinical trials targeting radioresistance are also summarized, reflecting the latest efforts to enhance therapeutic outcomes for TNBC patients.

乳腺癌是全世界女性中最常见和最致命的癌症。在不同的亚型中，三阴性乳腺癌（TNBC）是最具侵袭性的一种，对包括化疗、放疗和免疫治疗在内的治疗具有很高的耐药性。放疗仍然是TNBC的标准治疗方法，在减少局部复发方面有显著的好处。然而，对放射治疗的耐药性仍然是主要挑战，限制了其有效性并缩小了治疗选择。TNBC的放射耐药是由肿瘤细胞内在机制和肿瘤免疫微环境（TIME）相关过程驱动的。从本质上讲，TNBC细胞采用的策略包括增强的DNA损伤修复机制、肿瘤缺氧适应、生存途径的激活以及癌症干细胞和细胞外囊泡的贡献。从外部来看，TIME可以通过募集免疫抑制细胞（髓源性抑制细胞、巨噬细胞、中性粒细胞和调节性T细胞）和释放损害T细胞和自然杀伤细胞介导的抗肿瘤免疫反应的因子来进一步加剧耐药性。本文综述了肿瘤细胞特异性机制和时间动力学在TNBC放射耐药中的双重作用。我们进一步讨论了免疫系统在放射反应中的矛盾作用，强调了新兴的联合疗法，并解决了将这些策略转化为临床应用的挑战。正在进行的针对放射耐药的临床试验也进行了总结，反映了最新的努力，以提高TNBC患者的治疗结果。

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引用次数: 0

Fecal microbiota transplantation to enhance cancer treatment outcomes across different cancer types: A systematic literature review 粪便微生物群移植提高不同癌症类型的癌症治疗效果：系统文献综述。

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-25 DOI: 10.1016/j.ctrv.2025.103025

Demi Wekking , Tom van den Ende , Maarten F. Bijlsma , Andrés Vidal-Itriago , Max Nieuwdorp , Hanneke W.M. van Laarhoven

Background

The gut microbiome is increasingly recognized as a critical modulator of cancer therapy response. This systematic review evaluates Fecal Microbiota Transplantation (FMT)’s impact on cancer treatment outcomes and treatment-related toxicity and explores its mode of action.

Methods

A systematic search was conducted for prospective or retrospective clinical studies published until May 2025 that investigated FMT in cancer patients undergoing immunotherapy, chemotherapy, radiotherapy, targeted therapy, or a combination regimen.

Results

45 studies were included. No large-scale RCTs with published efficacy data were available, and most findings were derived from studies that lacked statistical power to assess efficacy. The majority of the articles demonstrated the safety and feasibility of FMT. Most toxicities reported were grade 1 or 2. Mechanistically, donor FMT restores gut microbiota diversity and reprograms the gut ecosystem, with increases in tumor-infiltrating lymphocytes and lower levels of regulatory T cells being observed. Furthermore, studies reported clinical improvement and endoscopic and/or histologic remission of treatment-induced colitis following FMT, alongside decreased colonic CD8+ T cell infiltration.

Conclusion

Donor FMT appears to be a safe and feasible adjunctive strategy during both first and later-line therapy and has potential for managing treatment-related colitis; however, its efficacy and its role in preventing immune-related adverse events remain to be elucidated in RCTs, as well as its application for graft-versus-host disease. The variability in clinical outcomes and context-dependent microbiota-host interactions that result in inconsistent findings underscores the complexity of FMT as a therapeutic modality. Furthermore, subclassifying recipient cancer patients could (based on gut microbiome ecosystem features) enhance biomarker identification for treatment responses.

背景：肠道微生物组越来越被认为是癌症治疗反应的关键调节剂。本系统综述评估了粪便微生物群移植（FMT）对癌症治疗结果和治疗相关毒性的影响，并探讨了其作用模式。方法：系统检索到2025年5月之前发表的前瞻性或回顾性临床研究，这些研究调查了接受免疫治疗、化疗、放疗、靶向治疗或联合治疗的癌症患者的FMT。结果：纳入45项研究。没有发表疗效数据的大规模随机对照试验，大多数研究结果来自缺乏评估疗效的统计能力的研究。大多数文章论证了FMT的安全性和可行性。报告的大多数毒性为1级或2级。从机制上讲，供体FMT恢复肠道微生物群多样性并重新编程肠道生态系统，观察到肿瘤浸润淋巴细胞增加和调节性T细胞水平降低。此外，研究报告了FMT后治疗性结肠炎的临床改善和内镜和/或组织学缓解，同时结肠CD8+ T细胞浸润减少。结论：在一线和后期治疗中，供体FMT似乎是一种安全可行的辅助策略，并具有管理治疗相关性结肠炎的潜力；然而，其在预防免疫相关不良事件中的作用及其在移植物抗宿主病中的应用仍有待于在随机对照试验中阐明。临床结果的可变性和环境依赖的微生物-宿主相互作用导致不一致的结果，强调了FMT作为一种治疗方式的复杂性。此外，对受体癌症患者进行亚分类（基于肠道微生物组生态系统特征）可以增强对治疗反应的生物标志物识别。

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引用次数: 0

Impact of brain metastases on systemic renal cell carcinoma treatment outcomes: A systematic literature review 脑转移对全身性肾细胞癌治疗结果的影响：系统文献综述

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-24 DOI: 10.1016/j.ctrv.2025.103024

Natalie Charnley , Kate Fife , Daniel Y.C. Heng , James Larkin , John McGrane , Sylvie Négrier , Naveen Vasudev , Balaji Venugopal , Alison Chisholm , Alessia Ogareva , Áine Prendergast , Laurence Albiges

Introduction

Brain metastases (BrM) are a negative prognostic factor in renal cell carcinoma (RCC) populations. Patients with RCC and BrM (RCC BrM + ) may receive systemic therapy and/or brain-targeted (local) treatment. We performed a systematic literature review to identify clinical trials and non-interventional studies reporting data on BrM impact on systemic treatment outcomes in patients with RCC.

Methods

We systematically searched the MEDLINE and Embase databases in January 2024 for publications reporting efficacy/effectiveness and/or safety/tolerability outcomes by BrM status from phase 2 and phase 3 clinical trials and non-interventional studies of systemic RCC therapies. Data were extracted from publications meeting predefined criteria (PROSPERO registration, CRD42023494896) and reported in accordance with PRISMA guidelines.

Results

Sixty-two publications (of 651 screened) were eligible (4 from prospective trials) and included 4,637 patients with RCC BrM + treated with systemic therapy. The most evaluated systemic therapies were sunitinib, nivolumab, ipilimumab + nivolumab, cabozantinib and sorafenib. Tolerability was generally consistent with known safety profiles in RCC trial populations. In the clinical trials, systemic treatment benefits for patients with RCC BrM + were equivocal. In non-interventional studies, survival was generally poorer in patients with RCC BrM + than reference groups (overall/BrM–). Survival and intracranial control benefits in patients with RCC BrM + were reported for some multimodal (systemic plus local) treatment strategies. There were no robust comparative data to guide systemic treatment selection.

Conclusion

We identified a need for robust data on intracranial and extracranial responses to systemic therapy in patients with RCC BrM+, taking into account prior local therapy exposure.

脑转移（BrM）是肾细胞癌（RCC）人群的一个负面预后因素。RCC和BrM （RCC BrM +）患者可接受全身治疗和/或脑靶向（局部）治疗。我们进行了系统的文献综述，以确定报告BrM对RCC患者全身治疗结果影响的临床试验和非介入性研究。方法：我们于2024年1月系统地检索了MEDLINE和Embase数据库，从系统性RCC治疗的2期和3期临床试验和非介入性研究中，根据BrM状态报告疗效/有效性和/或安全性/耐受性结果的出版物。数据从符合预定义标准的出版物中提取（PROSPERO注册号，CRD42023494896），并按照PRISMA指南进行报告。结果62篇（筛选的651篇）出版物（4篇来自前瞻性试验）符合条件，包括4,637例接受全身治疗的RCC BrM +患者。评估最多的全身疗法是舒尼替尼、纳武单抗、伊匹单抗+纳武单抗、卡博赞替尼和索拉非尼。在碾压细胞试验人群中，耐受性与已知的安全性基本一致。在临床试验中，RCC BrM +患者的全身治疗效果尚不明确。在非介入性研究中，RCC BrM +患者的生存率通常低于对照组（总体/BrM -）。一些多模式（全身加局部）治疗策略对RCC BrM +患者的生存和颅内控制有好处。没有可靠的比较数据来指导系统的治疗选择。结论：考虑到先前的局部治疗暴露，我们确定需要关于RCC BrM+患者对全身治疗的颅内和颅外反应的可靠数据。

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引用次数: 0

Genomic distinctions in adolescent and young adult cancer: A comprehensive review 青少年和青年癌症的基因组差异：一项全面的综述

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-20 DOI: 10.1016/j.ctrv.2025.103021

Jeffrey van Putten , Lina H. Lankhorst , Adrianus Johannes de Langen , Anthonie J. van der Wekken , Jeanine Roodhart , Karen Bolhuis , Sjoukje F. Oosting , Marloes van Dongen , Marleen Kok , Marjolein Geurts , Johan A.F. Koekkoek , Edwin Cuppen , Hilde H. Nienhuis , Winette T.A. van der Graaf

Cancer in Adolescents and Young Adults (AYAs) represents a unique biological intersection, encompassing malignancies typical of both paediatric and older adults, as well as age-specific cancers. Yet, diagnostic and treatment approaches are not tailored to AYAs, potentially overlooking age-specific molecular characteristics. This review examines genomic differences between AYAs and paediatric and older patients, emphasising trends in cancer driver genes and identifying knowledge gaps that limit our understanding of AYA cancer biology.

Across studies and cancer types, the AYA age range varies but is typically defined as 15–39 years. Remarkably, for nearly half of cancers diagnosed in AYAs, little or no literature exists on genomic differences or similarities compared to other age groups. Common cancers like testicular cancer and gynaecological cancer are underrepresented, while other typical AYA cancers such as thyroid cancer entirely lack comparative literature. In contrast, less common AYA cancers such as lung cancer and colorectal cancer are investigated extensively. Although genomic differences are reported across cancer types and in pan-cancer analyses, findings are often not generalisable to relevant subtypes or inconsistent, and insights gained are limited by the use of single-gene assays or small gene panels.

This review reveals an imbalance between the global incidence of AYA cancers and the scope of comparative genomic studies, as well as a lack of broader comprehensive molecular profiling. Addressing these gaps through broader genomic research, particularly in underexplored cancers, is essential to determine whether AYA tumour biology is indeed distinctive, and how age-appropriate, genomics-driven precision oncology should be delivered.

青少年和年轻人的癌症（AYAs）代表了一个独特的生物学交叉点，包括儿科和老年人典型的恶性肿瘤，以及年龄特异性癌症。然而，诊断和治疗方法并不是针对aya量身定制的，可能会忽略年龄特异性分子特征。这篇综述检查了AYA与儿科和老年患者之间的基因组差异，强调了癌症驱动基因的趋势，并确定了限制我们对AYA癌症生物学理解的知识差距。在不同的研究和癌症类型中，AYA的年龄范围各不相同，但通常定义为15-39岁。值得注意的是，与其他年龄组相比，近一半的aya患者诊断出的癌症，很少或根本没有关于基因组差异或相似性的文献。常见的癌症，如睾丸癌和妇科癌的代表性不足，而其他典型的AYA癌症，如甲状腺癌，完全缺乏比较文献。相比之下，不太常见的AYA癌症，如肺癌和结直肠癌，得到了广泛的研究。尽管在癌症类型和泛癌症分析中报告了基因组差异，但研究结果往往不能推广到相关亚型或不一致，并且所获得的见解受到单基因测定或小基因小组使用的限制。这篇综述揭示了全球AYA癌症发病率与比较基因组研究范围之间的不平衡，以及缺乏更广泛的综合分子谱。通过更广泛的基因组研究来解决这些差距，特别是在未被充分探索的癌症中，对于确定AYA肿瘤生物学是否确实与众不同，以及如何提供适合年龄的、基因组学驱动的精确肿瘤学至关重要。

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引用次数: 0

Datopotamab deruxtecan: rational strategies, novel advancements, challenges, and future perspectives Datopotamab deruxtecan：理性策略、新进展、挑战和未来展望

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-18 DOI: 10.1016/j.ctrv.2025.103023

Vincenzo Di Lauro , Alessandro Rizzo , Margherita Tafuro , Emanuela Fina , Claudia Martinelli , Claudia Calderaio , Rossana Di Rienzo , Miriam Pirolo , Annarita Fanizzi , Raffaella Massafra , Michelino De Laurentiis

Antibody-drug conjugates have recently revolutionized the treatment scenario of several tumors, including breast cancer. Among these, Datopotamab deruxtecan (Dato-DXd) is an ADC composed of a humanized anti-TROP2 monoclonal antibody linked to a potent exatecan-derived topoisomerase I inhibitor payload, deruxtecan (DXd), via a plasma-stable, selectively cleavable linker. Dato-DXd has shown notable efficacy and an overall tolerable safety profile, according to available evidence. Herein, we provide an overview of the pharmacological features, mechanisms of action, clinical efficacy, and adverse events of Dato-DXd in breast cancer. Furthermore, the current review proposes strategies to optimize patient management and accelerate the clinical development of Dato-DXd in this setting.

抗体-药物偶联物最近彻底改变了包括乳腺癌在内的几种肿瘤的治疗方案。其中，Datopotamab deruxtecan （Dato-DXd）是一种ADC，由人源化抗trop2单克隆抗体组成，通过血浆稳定、选择性可切割的连接物与exatecan衍生的有效拓扑异构酶I抑制剂deruxtecan （DXd）连接。根据现有证据，Dato-DXd显示出显著的疗效和总体可耐受的安全性。本文就Dato-DXd治疗乳腺癌的药理特点、作用机制、临床疗效和不良事件进行综述。此外，本综述还提出了在这种情况下优化患者管理和加速Dato-DXd临床发展的策略。

引用次数: 0

Novel therapies targeting delta-like ligand 3 (DLL3) in pulmonary and gastroenteropancreatic neuroendocrine carcinomas 靶向δ样配体3 （DLL3）治疗肺和胃肠胰神经内分泌癌的新疗法

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-15 DOI: 10.1016/j.ctrv.2025.103022

María Alameda-Guijarro , Antonio Rueda-Lara , Gema Martin-Montalvo , Oliver Higuera , Laura Gutiérrez-Sainz , Diego Jiménez-Bou , Julia Villamayor , Javier de Castro , Ana Custodio , Pablo Pérez-Wert

引用次数: 0

Does the benefit of neoadjuvant chemotherapy at six months predict long-term outcomes in colon or rectal cancer? A meta-analysis of randomised studies 6个月时新辅助化疗的益处能否预测结肠癌或直肠癌的长期预后？随机研究的荟萃分析

IF 10.5 1区医学 Q1 ONCOLOGY

Cancer treatment reviews

Pub Date : 2025-09-10 DOI: 10.1016/j.ctrv.2025.103020

Joanna Socha , Wojciech Michalski , Rob Glynne-Jones , Bengt Glimelius , Krzysztof Bujko

Introduction

The RAPIDO and PRODIGE-23 randomised trials of neoadjuvant versus adjuvant chemotherapy for rectal cancer showed that disease-free survival (DFS) curves diverged early, suggesting that much of the benefit from neoadjuvant chemotherapy occurred within six months. We aimed to determine whether the DFS benefit at six months in trials evaluating neoadjuvant chemotherapy can predict the benefit at 36 months, and to compare the timing of DFS benefit in trials of neoadjuvant versus in those of adjuvant chemotherapy.

Material and methods

A systematic review identified ten randomised trials comparing neoadjuvant with adjuvant chemotherapy and 37 randomised trials of adjuvant chemotherapy eligible for meta-analysis in rectal or colon cancer. Absolute differences in DFS between experimental and control groups at six and 36 months were extracted from Kaplan–Meier curves. The increment in the DFS benefit between the sixth and 36th months was calculated.

Results

In neoadjuvant chemotherapy trials, DFS benefit at six months (3.7 %, 95 % confidence interval [CI]: 1.9 to 5.4) did not differ significantly from that at 36 months (4.1 %, 95 % CI: 2.0 to 6.3), and the pooled absolute increment in DFS benefit between the sixth and 36th months was only 0.8 % (95 % CI: −1.6 to 3.2). The DFS benefit emerged earlier in neoadjuvant than in adjuvant chemotherapy trials.

Conclusion

In randomised trials comparing neoadjuvant with adjuvant chemotherapy, most of the DFS benefit from neoadjuvant chemotherapy manifests itself within the first six months. Therefore, assessing DFS at six months may potentially serve as an early indicator of long-term efficacy.

RAPIDO和PRODIGE-23对直肠癌新辅助化疗与辅助化疗的随机试验显示，无病生存（DFS）曲线较早出现分歧，表明新辅助化疗的大部分益处发生在6个月内。我们的目的是确定评估新辅助化疗的试验中6个月时的DFS获益是否可以预测36个月时的获益，并比较新辅助化疗与辅助化疗试验中DFS获益的时间。材料和方法一项系统评价确定了10项比较新辅助化疗与辅助化疗的随机试验和37项辅助化疗的随机试验，适合用于直肠癌或结肠癌的荟萃分析。从Kaplan-Meier曲线中提取实验组和对照组在6个月和36个月时的DFS的绝对差异。计算第六个月至第36个月间生活津贴的增加额。结果在新辅助化疗试验中，6个月时的DFS获益（3.7%，95%可信区间[CI]: 1.9 ~ 5.4）与36个月时的DFS获益（4.1%,95% CI: 2.0 ~ 6.3）无显著差异，第6个月和第36个月间DFS获益的总绝对增量仅为0.8% （95% CI:−1.6 ~ 3.2）。与辅助化疗试验相比，新辅助化疗试验的DFS获益出现得更早。结论在比较新辅助化疗与辅助化疗的随机试验中，大多数DFS受益于新辅助化疗在前6个月内表现出来。因此，在6个月时评估DFS可能作为长期疗效的早期指标。

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