Critical reviews in oncology/hematology最新文献_第3页

Digital twins in oncology: From predictive modelling to personalised treatment strategies 肿瘤学中的数字双胞胎：从预测建模到个性化治疗策略。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-30 DOI: 10.1016/j.critrevonc.2026.105171

David B. Olawade , Emmanuel O. Oisakede , Oluwakemi Jumoke Bello , Claret Chinenyenwa Analikwu , Eghosasere Egbon , Adeyinka Ojo

The digital twin (DT) concept, originating from engineering disciplines, has emerged as a transformative technology in healthcare, particularly in oncology. A digital twin creates a dynamic, virtual replica of a patient's physiological and pathological state, integrating multi-dimensional data to enable personalised cancer care. Despite growing interest, comprehensive reviews examining the breadth of DT applications in oncology remain limited. This narrative review aims to synthesise current evidence on digital twin applications in oncology, evaluate their potential to transform cancer care delivery, and identify challenges hindering clinical translation. A comprehensive literature search was conducted across PubMed, Scopus, Web of Science, and IEEE Xplore databases from inception to September 2025. Studies describing DT development, validation, or application in any cancer type were included. Grey literature, conference proceedings, and expert commentaries were also reviewed to capture emerging trends. Digital twins demonstrate applications across the cancer care continuum, including precision treatment selection, radiotherapy optimisation, drug development, immuno-oncology modelling, surgical planning, and survivorship care. Integration of multi-omics data, imaging biomarkers, and artificial intelligence enables dynamic simulation of tumour behaviour and treatment response. However, challenges persist in data integration, model validation, computational scalability, and ethical governance. Digital twin technology holds substantial promise for advancing precision oncology through predictive, personalised, and adaptive care strategies. Addressing current limitations through interdisciplinary collaboration and regulatory framework development is essential for clinical implementation.

数字孪生（DT）概念起源于工程学科，已成为医疗保健，特别是肿瘤学领域的变革性技术。数字双胞胎创建了患者生理和病理状态的动态虚拟副本，整合了多维数据，以实现个性化的癌症治疗。尽管人们对DT的兴趣越来越大，但对其在肿瘤学应用的广泛程度的全面审查仍然有限。这篇叙述性综述旨在综合目前关于数字双胞胎在肿瘤学中的应用的证据，评估它们改变癌症护理交付的潜力，并确定阻碍临床转化的挑战。从成立到2025年9月，对PubMed、Scopus、Web of Science和IEEE explore数据库进行了全面的文献检索。研究描述了DT在任何癌症类型中的发展、验证或应用。还审查了灰色文献、会议记录和专家评论，以捕捉新趋势。数字双胞胎展示了在癌症治疗连续体中的应用，包括精确治疗选择、放疗优化、药物开发、免疫肿瘤学建模、手术计划和生存护理。多组学数据、成像生物标志物和人工智能的集成使肿瘤行为和治疗反应的动态模拟成为可能。然而，在数据集成、模型验证、计算可扩展性和道德治理方面仍然存在挑战。数字孪生技术通过预测性、个性化和适应性护理策略，为推进精确肿瘤学提供了巨大的希望。通过跨学科合作和制定监管框架来解决当前的限制对于临床实施至关重要。

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引用次数: 0

Neoadjuvant PD-1/PD-L1 inhibitors plus chemotherapy in locally advanced gastric cancer: A systematic review and meta-analysis 局部晚期胃癌的新辅助PD-1/PD-L1抑制剂加化疗：系统回顾和荟萃分析

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-30 DOI: 10.1016/j.critrevonc.2026.105166

Zhenshun Li , Aqiang Fan , Jinqiang Liu , Wanli Yang , Lili Duan , Liaoran Niu , Chenyang Wang , Xi Chen , Yu Han , Liu Hong

Neoadjuvant immunochemotherapy (nICT) has emerged as a promising perioperative strategy for locally advanced gastric and gastroesophageal junction cancer (LAGC/EGJC), yet its survival benefit beyond pathological response and optimal patient selection remain uncertain. We conducted a systematic review and meta-analysis to evaluate the efficacy, safety, and biomarker stratification of nICT compared with neoadjuvant chemotherapy (nCT). PubMed, Embase, Web of Science, and the Cochrane Library were searched through August 30, 2025. Comparative studies of nICT versus nCT and single-arm nICT cohorts were included. Overall survival (OS) and recurrence-free survival (RFS) were primary outcomes. Fifteen comparative studies and thirty-four single-arm or biomarker datasets were included. Compared with nCT, nICT significantly improved OS (HR = 0.80, 95 % CI 0.70–0.92) and RFS (HR = 0.78, 95 % CI 0.69–0.87), and achieved higher pathological complete response, major pathological response, and R0 resection rates. Although treatment-related adverse events were more frequent with nICT, postoperative recovery and complication rates were comparable. Single-arm analyses showed pooled pathological complete and major pathological response rates of approximately 20 % and 43 %, with encouraging 2-year OS and RFS. Biomarker analyses demonstrated enrichment of pathological response in patients with PD-L1 CPS ≥ 1/≥ 5 and dMMR/MSI-H, whereas tumor mutational burden and Epstein–Barr virus status showed inconsistent discriminatory value. Meta-regression revealed no significant effect modification. Overall, nICT provides pathological and early survival improvement without compromising perioperative safety, supporting its integration into perioperative strategies for LAGC/EGJC.

新辅助免疫化疗（nICT）已成为局部晚期胃癌和胃食管结癌（LAGC/EGJC）的一种有希望的围手术期策略，但其生存效益超出病理反应和最佳患者选择仍不确定。我们进行了一项系统回顾和荟萃分析，以评估nICT与新辅助化疗（nCT）的有效性、安全性和生物标志物分层。PubMed、Embase、Web of Science和Cochrane Library的检索截止到2025年8月30日。纳入了nICT与nCT和单臂nICT队列的比较研究。总生存期（OS）和无复发生存期（RFS）是主要结局。纳入了15项比较研究和34项单臂或生物标志物数据集。与nCT相比，nICT显著改善了OS （HR = 0.80, 95% CI 0.70-0.92）和RFS (HR = 0.78, 95% CI 0.69-0.87)，实现了更高的病理完全缓解、主要病理缓解和R0切除率。虽然nICT治疗相关不良事件更频繁，但术后恢复和并发症发生率是相当的。单臂分析显示，合并病理完全缓解率和主要病理缓解率分别约为20%和43%，2年OS和RFS令人鼓舞。生物标志物分析显示PD-L1 CPS≥1/≥5和dMMR/MSI-H患者的病理反应丰富，而肿瘤突变负担和Epstein-Barr病毒状态显示不一致的区分价值。meta回归显示无显著的效应修正。总的来说，nICT在不影响围手术期安全性的情况下改善了病理和早期生存，支持将其纳入LAGC/EGJC的围手术期策略。

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引用次数: 0

Adjuvant aspirin and Cyclooxygenase-2 inhibitors in resected, PIK3CA-mutated colorectal cancer: A systematic review and meta-analysis of randomized controlled trials 阿司匹林和环氧化酶-2抑制剂在切除的、pik3ca突变的结直肠癌中的辅助治疗：随机对照试验的系统评价和荟萃分析

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-30 DOI: 10.1016/j.critrevonc.2026.105167

Ellen R. Blanchard-Cavagis , Pedro C. Abrahão Reis , Filipe Luis Vasconcelos Visani , Heloísa Carneiro Brito , Isabela C. Diniz , Caio Dabbous de Liz

Background

Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are widely available and inexpensive agents with proposed antitumor activity, particularly in tumors harboring PIK3CA mutations. This meta-analysis of randomized controlled trials (RCTs) evaluated whether adjuvant NSAID therapy improves outcomes in patients with resected PIK3CA-mutated colorectal cancer (CRC).

Methods

PubMed, Embase, and the Cochrane Library were systematically searched for RCTs assessing NSAID use following curative-intent resection of CRC in patients with confirmed PIK3CA mutations. Pooled hazard ratios (HRs) with corresponding 95 % confidence intervals (CIs) were calculated for disease-free survival (DFS) and overall survival (OS) using both fixed and random-effects models. Sensitivity analyses excluded participants with low-dose aspirin exposure concomitant with cyclooxygenase-2 (COX-2) inhibitors.

Results

Among 477 records screened, four RCTs met eligibility criteria, comprising 426 patients assigned to NSAIDs (aspirin or COX-2 inhibitors) and 363 receiving placebo. Adjuvant NSAID therapy improves DFS (HR 0.65; 95 % CI, 0.46–0.90). In sensitivity analyses excluding concomitant aspirin exposure, a similar magnitude of effect was observed (HR 0.57; 95 % CI, 0.39–0.83). The pooled OS analysis was not statistically significant (HR 0.78; 95 % CI, 0.39–1.57). Exclusion of low-dose aspirin users was associated with lower mortality risk (HR 0.54; 95 % CI, 0.30–0.99), although these findings should be interpreted cautiously.

Conclusion

Adjuvant NSAID therapy is associated with improved DFS in patients with PIK3CA-mutated CRC. OS benefit remains uncertain, and findings from sensitivity analyses are exploratory. These findings support consideration of NSAIDs as a biomarker-informed adjuvant strategy in selected patients while underscoring the need for confirmatory evidence from ongoing randomized trials.

背景：阿司匹林和其他非甾体抗炎药（NSAIDs）是广泛使用且价格低廉的抗肿瘤药物，特别是在PIK3CA突变的肿瘤中。这项随机对照试验（RCTs）的荟萃分析评估了辅助非甾体抗炎药治疗是否能改善切除的pik3ca突变的结直肠癌（CRC）患者的预后。方法：系统检索PubMed、Embase和Cochrane图书馆，以评估确诊的PIK3CA突变患者在治疗意图切除结直肠癌后使用非甾体抗炎药的随机对照试验。使用固定效应和随机效应模型计算无病生存期（DFS）和总生存期（OS）的合并风险比（hr）和相应的95%置信区间（ci）。敏感性分析排除了同时服用环氧化酶-2 （COX-2）抑制剂的低剂量阿司匹林暴露者。结果：在筛选的477条记录中，4项随机对照试验符合资格标准，其中426例患者被分配到非甾体抗炎药（阿司匹林或COX-2抑制剂）组，363例患者接受安慰剂组。辅助非甾体抗炎药治疗可改善DFS （HR 0.65; 95% CI, 0.46-0.90）。在排除伴随阿司匹林暴露的敏感性分析中，观察到类似程度的影响（HR 0.57; 95% CI, 0.39-0.83）。合并OS分析无统计学意义（HR 0.78; 95% CI, 0.39-1.57）。排除低剂量阿司匹林使用者与较低的死亡风险相关（HR 0.54; 95% CI, 0.30-0.99），尽管这些发现应谨慎解释。结论：辅助非甾体抗炎药治疗可改善pik3ca突变的结直肠癌患者的DFS。OS的益处仍然不确定，敏感性分析的结果是探索性的。这些发现支持将非甾体抗炎药作为特定患者的生物标志物辅助策略的考虑，同时强调需要从正在进行的随机试验中获得确证证据。

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引用次数: 0

Circular RNA-mediated tumor immune escape: Mechanistic architecture and nanomedicine-enabled therapeutic reprogramming 环状rna介导的肿瘤免疫逃逸：机制结构和纳米医学支持的治疗性重编程。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-29 DOI: 10.1016/j.critrevonc.2026.105159

Shenyi Jiang , Yan Li , Di Wu , Ling Zhang , Xin Tian , Fandong Meng

Circular RNAs (circRNAs) have emerged as pivotal regulators of tumor immune escape, acting through multilayered mechanisms that include miRNA sequestration, RNA-binding protein scaffolding, m⁶A-dependent stabilization, metabolic rewiring, and exosomal communication. These processes collectively sustain PD-L1 expression and stability, drive CD8⁺ T-cell exhaustion, promote Treg and MDSC expansion, skew macrophages toward immunosuppressive M2 phenotypes, and reshape glycolytic and lipid metabolic pathways to generate an immune-refractory microenvironment. In parallel, exosomal circRNAs disseminate long-range immunosuppressive signals, reinforcing therapy resistance and systemic immune dysfunction. Conversely, a newly recognized subset of “immune-activating circRNAs” induces ferroptosis, immunogenic cell death, and STING-mediated innate immune activation, highlighting the dual nature of circRNA immunoregulation. Recent advances in nanomedicine—spanning lipid nanoparticles, polymeric platforms, and biomimetic membrane-coated carriers—have enabled precise silencing of oncogenic circRNAs and efficient delivery of synthetic therapeutic circRNAs, demonstrating potent synergy with immune checkpoint inhibitors, NK-cell therapy, STING agonists, and ferroptosis inducers. Although challenges remain, including delivery specificity, biosafety, biomarker standardization, and off-target effects, the convergence of circRNA biology and advanced nanotechnology presents a transformative opportunity to develop next-generation RNA-guided cancer immunotherapies. Together, these findings position circRNAs as both key mechanistic drivers of immune escape and promising therapeutic targets for nanomedicine-enabled precision immunotherapy.

环状rna （circRNAs）已成为肿瘤免疫逃逸的关键调节因子，通过多层机制起作用，包括miRNA隔离、rna结合蛋白支架、26 a依赖性稳定、代谢重连接和外体通讯。这些过程共同维持PD-L1的表达和稳定性，驱动CD8 + t细胞耗竭，促进Treg和MDSC扩增，使巨噬细胞偏向免疫抑制的M2表型，重塑糖酵解和脂质代谢途径，从而产生免疫难解的微环境。与此同时，外泌体环状rna传播远程免疫抑制信号，加强治疗抵抗和全身免疫功能障碍。相反，一种新发现的“免疫激活环状rna”亚群诱导铁凋亡、免疫原性细胞死亡和sting介导的先天免疫激活，凸显了环状rna免疫调节的双重性质。纳米医学的最新进展——包括脂质纳米颗粒、聚合物平台和仿生膜包覆载体——已经能够精确地沉默致癌环状rna，并有效地递送合成治疗性环状rna，证明了与免疫检查点抑制剂、nk细胞疗法、STING激动剂和铁凋亡诱导剂的有效协同作用。尽管仍然存在挑战，包括递送特异性、生物安全性、生物标志物标准化和脱靶效应，但circRNA生物学和先进纳米技术的融合为开发下一代rna引导的癌症免疫疗法提供了一个变革性的机会。总之，这些发现将circRNAs定位为免疫逃逸的关键机制驱动因素和纳米药物精准免疫治疗的有希望的治疗靶点。

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引用次数: 0

Diagnostic and prognostic significance of circulating HPV cfDNA in cervical cancer: A systematic review and meta-analysis 循环HPV cfDNA在宫颈癌中的诊断和预后意义：系统综述和荟萃分析。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-29 DOI: 10.1016/j.critrevonc.2026.105161

Preetiparna Parida , Ankita Mehta , Elstin Anbu Raj , Shyamala Guruvare , Mahadev Rao , Rama Rao Damerla , Shirley Lewis

Importance

Human papillomavirus circulating free DNA (HPV cfDNA) is an emerging biomarker with potential utility in the detection and treatment monitoring of cervical cancer.

Objective

To conduct a systematic review and meta-analysis evaluating the diagnostic and prognostic performance of HPV cfDNA in cervical cancer.

Methods

A comprehensive literature search was conducted in PubMed, CINAHL, Cochrane Library, Scopus, and Embase through April 2025. Eligible studies reported or allowed calculation of diagnostic performance of HPV cfDNA in HPV-positive cervical cancer patients and/or included serial HPV cfDNA testing during post-treatment follow-up. Meta-analyses were conducted using a random-effects model. Heterogeneity was assessed with the I² statistic. The review followed PRISMA guidelines, and study quality was assessed using QUADAS-2.

Results

Of 106 studies screened, 20 met the inclusion criteria. Eleven studies contributed to the diagnostic meta-analysis and six to the prognostic analysis. The pooled sensitivity and specificity of HPV cfDNA for cervical cancer detection were 0.47 (95 % CI, 0.43–0.52) and 0.96 (95 % CI, 0.92–0.98), respectively. Positive and negative likelihood ratios were 10.49 and 0.28, with a diagnostic odds ratio of 71.31. The area under the SROC curve was 0.9825, indicating excellent overall diagnostic performance. Prognostically, HPV cfDNA positivity at 3 months post-treatment was significantly associated with reduced progression-free survival (HR = 8.50; 95 % CI, 4.69–15.41; I² = 0 %).

Conclusions and relevance

HPV cfDNA shows high specificity and strong prognostic value, supporting its clinical utility in cervical cancer detection and treatment surveillance.

重要性：人乳头瘤病毒循环游离DNA （HPV cfDNA）是一种新兴的生物标志物，在宫颈癌的检测和治疗监测中具有潜在的用途。目的：通过系统回顾和荟萃分析，评价HPV cfDNA在宫颈癌中的诊断和预后表现。方法：到2025年4月，在PubMed、CINAHL、Cochrane Library、Scopus和Embase中进行全面的文献检索。符合条件的研究报告或允许计算HPV阳性宫颈癌患者的HPV cfDNA诊断性能和/或包括治疗后随访期间的连续HPV cfDNA检测。采用随机效应模型进行meta分析。异质性评价采用I²统计量。研究遵循PRISMA指南，使用QUADAS-2评估研究质量。结果：筛选的106项研究中，20项符合纳入标准。11项研究用于诊断荟萃分析，6项用于预后分析。HPV cfDNA检测宫颈癌的总敏感性和特异性分别为0.47 （95% CI, 0.43-0.52）和0.96 （95% CI, 0.92-0.98）。阳性和阴性似然比分别为10.49和0.28，诊断优势比为71.31。SROC曲线下面积为0.9825，总体诊断效果良好。在预后方面，治疗后3个月HPV cfDNA阳性与无进展生存期降低显著相关（HR = 8.50; 95% CI, 4.69-15.41; I²= 0%）。结论及意义：HPV cfDNA具有高特异性和较强的预后价值，支持其在宫颈癌检测和治疗监测中的临床应用。

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引用次数: 0

Research training in radiation oncology: a scoping review of global pathways, barriers and enablers 放射肿瘤学的研究培训：全球途径、障碍和推动因素的范围审查。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-29 DOI: 10.1016/j.critrevonc.2026.105162

Joanna Kucharczak , Anushka Irodi , Katie Spencer , Gerard M. Walls , Christopher M. Jones

Background

There is a disparity between the importance of radiation oncology (RO) to cancer care and the research activity that underpins it. This may relate to inadequate availability of, or barriers within, residency research training. This scoping review sought to characterize the barriers and enablers to RO research training, and to summarize relevant training pathways.

Methods

Systematic Medline and Embase searches were conducted using “RO”, “research”, “training”, and related terms, to identify reports published between 2010 and 2025. Manuscripts were screened using predefined inclusion and exclusion criteria to select those describing research initiatives, and barriers and enablers to resident-level research. These features were extracted along with country of origin and study design parameters.

Results

Of 1745 identified manuscripts, 54 were included. Most reports originated from North America (n = 24/54; 44.4 %), Europe (n = 12/54; 22.2 %) and Australasia (n = 8/54; 14.8 %). A majority were survey-based studies (n = 27/54; 50.0 %) or observational cohort analyses (n = 10/54; 18.5 %). We identified seven countries with mandated resident-level research training and three regions/countries with RO-specific physician scientist training programs. These varied from integrated training schemes that include higher research degree completion, to short-interval initiatives. Five programs were supported by metrics detailing their impact. Reported enablers and barriers demonstrated a subtle geographic variation but included protected time and funding, mentorship and attainment of research skills.

Conclusion

There is global variation in research training during RO residency but numerous shared enablers and barriers. These data provide shared best practice and a scaffold on which national and international societies can build improved research training pathways to redress the radiation research deficit.

背景：放射肿瘤学（RO）对癌症治疗的重要性与支持它的研究活动之间存在差异。这可能与住院医师研究培训的可用性不足或存在障碍有关。这一范围审查试图描述RO研究培训的障碍和推动因素，并总结相关的培训途径。方法：使用“RO”、“research”、“training”及相关术语进行系统的Medline和Embase检索，识别2010-2025年间发表的报告。使用预定义的纳入和排除标准筛选手稿，以选择那些描述研究计划、障碍和促进居民水平研究的因素。这些特征与原产国和研究设计参数一起被提取出来。结果：在1745份鉴定的手稿中，54份被收录。大多数报告来自北美（n=24/54; 44.4%）、欧洲（n=12/54; 22.2%）和澳大拉西亚（n=8/54; 14.8%）。大多数是基于调查的研究（n=27/54; 50.0%）或观察性队列分析（n=10/54; 18.5%）。我们确定了7个国家有强制性的住院医师水平的研究培训，3个地区/国家有专门针对ro的医师科学家培训项目。这些计划从包括完成更高研究学位的综合培训计划到短期计划不等。五个项目得到了详细说明其影响的指标的支持。报告的促成因素和障碍显示出细微的地理差异，但包括受保护的时间和资金、指导和获得研究技能。结论：在RO驻留期间的研究培训存在全球差异，但有许多共同的促成因素和障碍。这些数据提供了共享的最佳做法和一个框架，国家和国际社会可以在此基础上建立改进的研究培训途径，以弥补辐射研究的不足。

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引用次数: 0

Artificial intelligence and multi-omics convergence in breast cancer: Revolutionizing diagnosis, prognostication, and precision oncology 人工智能和多组学在乳腺癌中的融合：革命性的诊断、预测和精确肿瘤学

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-29 DOI: 10.1016/j.critrevonc.2026.105160

Bitao Jiang , Yuefei Wu , Xiao Chen , Chunyan Jian , Wenjuan Wang

Breast cancer (BC) is a highly heterogeneous malignancy and remains a major cause of cancer-related mortality among women worldwide. Advances in multi-omics profiling spanning genomics, transcriptomics, epigenomics, proteomics, and metabolomics have enabled finer subtype stratification and more comprehensive characterisation of tumour biology, thereby accelerating the discovery of diagnostic and prognostic biomarkers and actionable therapeutic targets. Nonetheless, translating multi-layer molecular signals into clinically robust decision support remains challenging because of the high dimensionality and heterogeneity of omics data, cross-cohort and cross-platform variability, and the fragmentation inherent to single-modality analyses. This review summarises how multi-omics studies have refined BC subtype definitions and advanced biomarker and target identification, and then synthesises recent progress in artificial intelligence, particularly deep learning, for integrating multi-omics with imaging, pathology, and clinical variables to improve diagnosis, risk stratification, prognosis prediction, and treatment response assessment. We critically examine representative multimodal integration frameworks and emerging deep learning architectures that learn both shared and modality-specific representations, which in many settings enable more accurate patient-level prediction than unimodal baselines. We further delineate key barriers to clinical translation, including cross-centre heterogeneity and inconsistent endpoint definitions, structural missingness of modalities in real-world workflows, inadequate cross-platform normalisation, limited interpretability and auditability, and a lack of prospective validation. Finally, we propose realistic next steps, including standardised and auditable preprocessing pipelines, missingness-aware fusion strategies, explainable and uncertainty-aware modelling, privacy-preserving multi-centre learning, and prospective, workflow-based evaluation. Collectively, these perspectives provide a roadmap for advancing multimodal AI–multi-omics integration toward reliable clinical deployment in BC management.

乳腺癌（BC）是一种高度异质性的恶性肿瘤，仍然是世界范围内妇女癌症相关死亡的主要原因。跨越基因组学、转录组学、表观基因组学、蛋白质组学和代谢组学的多组学分析取得了进展，使得更精细的亚型分层和更全面的肿瘤生物学特征得以实现，从而加速了诊断和预后生物标志物以及可行治疗靶点的发现。然而，由于组学数据的高维性和异质性、跨队列和跨平台的可变性以及单模态分析固有的碎片性，将多层分子信号转化为临床可靠的决策支持仍然具有挑战性。本文综述了多组学研究如何改进BC亚型定义和先进的生物标志物和靶点识别，然后综合了人工智能的最新进展，特别是深度学习，将多组学与影像学、病理学和临床变量相结合，以改善诊断、风险分层、预后预测和治疗反应评估。我们批判性地研究了代表性的多模态集成框架和新兴的深度学习架构，这些架构可以学习共享和特定于模态的表示，在许多情况下，它们比单模态基线能够更准确地预测患者水平。我们进一步描述了临床翻译的主要障碍，包括跨中心异质性和不一致的终点定义，现实世界工作流程中模式的结构性缺失，跨平台规范化不足，可解释性和可审计性有限，以及缺乏前瞻性验证。最后，我们提出了现实的下一步措施，包括标准化和可审计的预处理管道，缺失感知融合策略，可解释和不确定性感知建模，保护隐私的多中心学习，以及前瞻性的，基于工作流的评估。总的来说，这些观点为推进多模式人工智能-多组学集成在BC管理中的可靠临床部署提供了路线图。

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引用次数: 0

Trastuzumab deruxtecan in non-breast solid tumors: Expanding indications, efficacy, and future directions 曲妥珠单抗在非乳腺实体肿瘤中的应用：扩大适应症、疗效和未来方向。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-28 DOI: 10.1016/j.critrevonc.2026.105158

A. Ghidini , R. Bukovec , L. Roncari , L. Dottorini , F. Petrelli

Background

HER2 alterations occur across multiple malignancies beyond breast cancer, including gastric, non-small-cell lung, colorectal, gynecologic, salivary gland, biliary tract, and urothelial cancers. Trastuzumab deruxtecan (T-DXd), a next-generation antibody–drug conjugate, has transformed outcomes through its high drug-to-antibody ratio, potent topoisomerase I inhibitor payload, and membrane-permeable design enabling a bystander effect.

Methods

We reviewed clinical and translational evidence for T-DXd in non-breast solid tumors, focusing on efficacy, safety, biomarkers, and resistance mechanisms. Key data were derived from the DESTINY trial program, basket studies, and recent regulatory submissions.

Results

Across tumor types, T-DXd has demonstrated clinically meaningful response rates: ∼55 % in HER2-mutant NSCLC, 42–51 % in gastric cancer, 37–45 % in colorectal cancer, 57 % in endometrial cancer, and ∼60 % in salivary duct carcinoma. Durable responses have also been observed in biliary and urothelial cancers. The most frequent adverse events are gastrointestinal and hematologic, while interstitial lung disease remains the most significant toxicity, occurring in ∼10–15 % of patients, with rare fatal cases. Predictive biomarkers vary by histology: HER2 mutation is most relevant in NSCLC, whereas amplification and overexpression define benefit in gastrointestinal and gynecologic malignancies. Resistance mechanisms include HER2 downregulation, bypass signaling activation, and impaired payload release.

Conclusions

T-DXd has emerged as a transformative therapy across HER2-driven malignancies, leading to histology-specific and tissue-agnostic approvals. Vigilant ILD monitoring is essential, and further research is warranted to refine biomarkers, address resistance, and explore rational drug combinations. T-DXd exemplifies the paradigm shift of antibody–drug conjugates toward pan-cancer precision oncology.

背景：HER2改变发生在乳腺癌以外的多种恶性肿瘤中，包括胃癌、非小细胞肺癌、结直肠癌、妇科、唾液腺癌、胆道癌和尿路上皮癌。曲妥珠单抗德鲁西替康（T-DXd）是下一代抗体-药物偶联物，通过其高药抗比、有效的拓扑异构酶I抑制剂有效载荷和膜渗透设计实现旁观者效应，已经改变了结果。方法：我们回顾了T-DXd治疗非乳腺实体肿瘤的临床和转化证据，重点关注其疗效、安全性、生物标志物和耐药机制。关键数据来自DESTINY试验项目、一揽子研究和最近提交的监管文件。结果：在不同的肿瘤类型中，T-DXd已显示出具有临床意义的应答率：her2突变型NSCLC的应答率约为55%，胃癌的应答率为42-51%，结直肠癌的应答率为37-45%，子宫内膜癌的应答率为57%，涎腺管癌的应答率为60%。在胆道和尿路上皮癌中也观察到持久的反应。最常见的不良事件是胃肠道和血液学，而肺间质性疾病仍然是最显著的毒性，发生在约10-15%的患者中，罕见的死亡病例。预测生物标志物因组织学而异：HER2突变与非小细胞肺癌最相关，而扩增和过表达则对胃肠道和妇科恶性肿瘤有益处。抗性机制包括HER2下调、旁路信号激活和有效载荷释放受损。结论：T-DXd已成为her2驱动型恶性肿瘤的变革性治疗方法，导致组织特异性和组织不可见性的批准。警惕ILD监测是必要的，需要进一步的研究来完善生物标志物，解决耐药性问题，并探索合理的药物组合。T-DXd体现了抗体-药物偶联物向泛癌症精确肿瘤学的范式转变。

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引用次数: 0

Recent advances in systemic treatment for HER2-negative breast cancer with brain metastases her2阴性乳腺癌脑转移全身治疗的最新进展。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-27 DOI: 10.1016/j.critrevonc.2026.105156

Chunfang Hao , Jie Zhang , Yuehong Zhu

Human epidermal growth factor receptor 2 (HER2) -negative breast cancer brain metastases (BCBM) and leptomeningeal disease (LMD) pose significant clinical challenges due to limited treatment options and poor prognosis. Unlike HER2-positive BCBM, which has established therapeutic protocols, HER2-negative BCBM and LMD lacks standardized approaches. Recent advances have introduced novel systemic therapies targeting diverse pathways, including cell cycle regulation, DNA repair, immune modulation, vascular suppression, and leptomeningeal penetration, with emerging data supporting activity in LMD. Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors show promise in hormone receptor-positive subsets, particularly when combined with radiotherapy. Antibody-drug conjugates (ADCs), such as trastuzumab deruxtecan and sacituzumab govitecan, demonstrate enhanced central nervous system penetration and tumor-specific cytotoxicity, improving outcomes in both stable and active brain metastases. Immune checkpoint inhibitors (ICIs) and poly (ADP-ribose) polymerase (PARP) inhibitors also exhibit potential, though their efficacy varies by molecular subtype. Additionally, intrathecal therapies have become a cornerstone for LMD management, bypassing the blood-CSF barrier. Emerging therapies like selective estrogen receptor degraders (SERDs) and kinase inhibitors address resistance mechanisms, offering new avenues for personalized treatment. This review underscores the need for survival-prolonging, quality-of-life-preserving strategies with optimized safety profiles, highlighting the evolving landscape of HER2-negative BCBM and LMD management.

人表皮生长因子受体2 （HER2）阴性乳腺癌脑转移（BCBM）和轻脑膜病（LMD）由于治疗方案有限和预后差，给临床带来了重大挑战。与已建立治疗方案的her2阳性BCBM不同，her2阴性BCBM和LMD缺乏标准化方法。最近的进展引入了针对多种途径的新型全身疗法，包括细胞周期调节、DNA修复、免疫调节、血管抑制和轻脑膜渗透，新出现的数据支持LMD的活性。细胞周期蛋白依赖性激酶4/6 （CDK4/6）抑制剂在激素受体阳性亚群中显示出希望，特别是当与放疗联合使用时。抗体-药物偶联物（adc），如曲妥珠单抗德鲁德替康和sacituzumab govitecan，显示出增强中枢神经系统渗透和肿瘤特异性细胞毒性，改善稳定和活动性脑转移的预后。免疫检查点抑制剂（ICIs）和聚（adp -核糖）聚合酶（PARP）抑制剂也表现出潜力，尽管它们的功效因分子亚型而异。此外，鞘内治疗已成为LMD治疗的基石，绕过血- csf屏障。选择性雌激素受体降解剂（serd）和激酶抑制剂等新兴疗法解决了耐药性机制，为个性化治疗提供了新的途径。这篇综述强调了对具有优化安全性的延长生存、保持生活质量策略的需求，强调了her2阴性BCBM和LMD管理的不断发展的前景。

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引用次数: 0

Death receptor 3: A paradoxical biomarker and therapeutic target in pan-cancer 死亡受体3：一个矛盾的生物标志物和泛癌症的治疗靶点

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2026-01-26 DOI: 10.1016/j.critrevonc.2026.105157

Wenxuan Fang , Junfang Du , Zedong Xu , Qiuyu Liu , Yonghong Liu , Xueni Wang

Death receptor 3 (DR3/TNFRSF25) is a member of the tumor necrosis factor receptor superfamily, exhibiting dual roles in regulating tumor apoptosis and metastasis. Through literature review and pan-cancer analysis, this study reveals that DR3 expression exhibits distinct tumor type specificity: it is highly expressed in seven cancers, including Bladder Urothelial Carcinoma (BLCA), while showing low expression in sixteen cancers, such as Adrenocortical carcinoma (ACC). Its expression correlates with CD8⁺ T cell and natural killer (NK) cell infiltration, tumor mutational burden (TMB), and is closely associated with prognosis, exhibiting opposite trends across different cancer types. Mechanistically, DR3 activates apoptosis or programmed necrosis pathways by binding its ligand TL1A. Its interaction with NF-κB exhibits directional discrepancies across cancer types, which differentially regulate cell death. Additionally, DR3 suppresses angiogenesis and modulates antitumor immune responses. While multiple natural and synthetic compounds modulate DR3-related pathways to exert antitumor effects, no direct-targeting drugs are currently available. The presence of DR3 isoforms and decoy receptor DcR3 adds complexity to its signaling, suggesting that future clinical applications require precise evaluation considering the tumor microenvironment. In summary, DR3 is a multifunctional molecule with significant potential as a biomarker and therapeutic target. However, its duality and context-dependent effects necessitate the development of personalized strategies based on tumor molecular subtyping.

死亡受体3 （DR3/TNFRSF25）是肿瘤坏死因子受体超家族的成员，在调节肿瘤凋亡和转移中发挥双重作用。通过文献回顾和泛癌分析，本研究发现DR3表达具有明显的肿瘤类型特异性：在膀胱尿路上皮癌（BLCA）等7种肿瘤中高表达，在肾上腺皮质癌（ACC）等16种肿瘤中低表达。其表达与CD8 + T细胞和自然杀伤细胞（NK）浸润、肿瘤突变负荷（TMB）相关，且与预后密切相关，在不同癌症类型中表现出相反的趋势。在机制上，DR3通过结合其配体TL1A激活凋亡或程序性坏死途径。它与NF-κB的相互作用在不同的癌症类型中表现出方向性差异，从而不同地调节细胞死亡。此外，DR3抑制血管生成和调节抗肿瘤免疫反应。虽然多种天然和合成化合物可调节dr3相关途径发挥抗肿瘤作用，但目前尚无直接靶向的药物可用。DR3亚型和诱饵受体DcR3的存在增加了其信号传导的复杂性，这表明未来的临床应用需要考虑肿瘤微环境的精确评估。综上所述，DR3是一种多功能分子，具有作为生物标志物和治疗靶点的巨大潜力。然而，它的双重性和环境依赖效应需要基于肿瘤分子亚型的个性化策略的发展。

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引用次数: 0