Critical reviews in oncology/hematology最新文献_第7页

Dormancy in colorectal cancer: The functional core of resistance, metastasis, and relapse 结直肠癌的休眠：抵抗、转移和复发的功能核心

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-09 DOI: 10.1016/j.critrevonc.2025.105081

Eduardo Alvarado-Ortiz , Angela Patricia Moreno-Londoño , Miguel Ángel Sarabia-Sánchez

Current treatments for colorectal cancer (CRC) can induce apparent disease remission; unfortunately, CRC eventually relapses in many patients. CRC recurrence has been associated with the presence of dormant cancer cells, which are difficult to detect and are maintained in a resilient state characterized by a low cell cycling rate. Dormant cancer cells evade immune surveillance, are not eliminated by conventional therapy, and employ specific metabolic programs enabling them to remain hidden for extended periods. Furthermore, the period elapsed since the onset of the disease, represents the opportunity where tumor has early spread to distant sites. Importantly, cellular dormancy and awakening are also involved in metastasis. This review explores the nuanced mechanisms involved in cellular dormancy, from remnant cancer cells of the primary tumor to metastatic cancer cells. The insights in this field hold promise to contribute clinical innovations for the improvement of predictive biomarkers or targeted therapies. Indeed, we address cell dormancy by unifying a set of concepts from modern oncology in light of the unique characteristics of CRC. Here, we discuss the immune system, metabolic imbalance, and drug tolerance; the major challenges that dormant cancer cells must overcome once awakened. This review reinforces the translational value of cellular dormancy as the foremost cause of recurrence and poor prognosis in colorectal cancer, with the aim of guiding the development of potential emergent treatments that can be combined with existing approaches such as chemotherapy and immunotherapy.

目前对结直肠癌（CRC）的治疗可以诱导明显的疾病缓解；不幸的是，许多患者的结直肠癌最终会复发。CRC复发与休眠癌细胞的存在有关，这些癌细胞很难被发现，并且保持在一种以低细胞周期率为特征的弹性状态。休眠的癌细胞逃避免疫监视，不能被常规治疗消除，并利用特定的代谢程序使它们长时间隐藏。此外，自发病以来所经过的时间，代表肿瘤早期扩散到远处部位的机会。重要的是，细胞休眠和觉醒也与转移有关。这篇综述探讨了细胞休眠的微妙机制，从原发肿瘤的残余癌细胞到转移性癌细胞。该领域的见解有望为改善预测性生物标志物或靶向治疗的临床创新做出贡献。事实上，我们根据CRC的独特特征，通过统一现代肿瘤学的一套概念来解决细胞休眠问题。在这里，我们讨论免疫系统、代谢失衡和药物耐受性；休眠癌细胞必须克服的主要挑战一旦被唤醒。本综述强调了细胞休眠作为结直肠癌复发和预后不良的首要原因的翻译价值，旨在指导潜在的紧急治疗方法的开发，这些治疗方法可以与化疗和免疫治疗等现有方法相结合。

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引用次数: 0

Harnessing the effector-to-regulatory T cell ratio to advance prognosis and precision therapy in pancreatic cancer 利用效应-调节性T细胞比例促进胰腺癌的预后和精准治疗

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-09 DOI: 10.1016/j.critrevonc.2025.105076

Xuejun Guo , Huaibo Zhang , Liqin Yao , Wenxue Ma

Pancreatic cancer remains one of the most lethal malignancies, characterized by rapid progression, late-stage diagnosis, and resistance to current therapies. A major contributor to its poor prognosis is the highly immunosuppressive tumor microenvironment (TME), where regulatory T cells (Tregs) suppressing effector T cells (Teffs). The ratio of Teffs to Tregs (Teff/Treg ratio) has emerged as a pivotal biomarker that reflects immune balance within the TME, with significant prognostic and therapeutic relevance. A low Teff/Treg ratio correlates with poor clinical outcomes, immunotherapy resistance, and tumor progression. Elucidating the mechanisms regulating that regulate this ratio such as immune checkpoint pathways, cytokine-mediated signaling, and stromal interactions offers promising avenues to restore anti-tumor immunity. This review critically evaluates the prognostic values of the Teff/Treg ratio in pancreatic cancer, highlights emerging strategies to rebalance this axis, and outlines current challenges and research gaps. Standardizing measurement methodologies and integrating Teff/Treg analysis into pancreatic cancer-specific research are essential next steps toward precision immunotherapy.

胰腺癌仍然是最致命的恶性肿瘤之一，其特点是进展迅速，诊断晚期，对目前的治疗有耐药性。其预后不良的主要原因是高度免疫抑制的肿瘤微环境（TME），其中调节性T细胞（Tregs）抑制效应T细胞（Teffs）。Teff/Treg比率（Teff/Treg比率）已成为反映TME内免疫平衡的关键生物标志物，具有重要的预后和治疗相关性。较低的Teff/Treg比值与较差的临床结果、免疫治疗抵抗和肿瘤进展相关。阐明调节这一比例的机制，如免疫检查点途径、细胞因子介导的信号传导和基质相互作用，为恢复抗肿瘤免疫提供了有希望的途径。这篇综述批判性地评估了Teff/Treg比值在胰腺癌中的预后价值，强调了重新平衡这一轴的新策略，并概述了当前的挑战和研究空白。标准化测量方法和将Teff/Treg分析整合到胰腺癌特异性研究中是实现精准免疫治疗的关键步骤。

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引用次数: 0

Cyclin E1 as a driver of oncogenesis; high grade serous ovarian cancer as an exemplar Cyclin E1在肿瘤发生中的驱动作用以高级别浆液性卵巢癌为例。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-09 DOI: 10.1016/j.critrevonc.2025.105080

Sarah J. Taylor, Charlie Gourley

Cyclin E1 is a critical mediator of cell cycle dynamics, controlling G1/S phase transition in complex with CDK2. Overexpression of cyclin E1 can lead to replication stress, DNA damage, and heightened genomic instability. This is associated with oncogenesis, and is frequently observed pan-cancer; but is particularly common in high grade serous ovarian cancer (HGSOC). HGSOC exhibits a genomic landscape dominated by structural variation and instability, with high cyclin E1 expression in up to 58 % and CCNE1 amplification in up to 30 % of cases. HGSOC therefore represents an exemplar setting for investigating cyclin E dysregulation in cancer. HGSOC patients with high tumour expression of cyclin E1, in combination with copy number amplification, experience particularly poor survival. Agents targeting CDK2, WEE1, and PYMKT1, and other cell cycle associated targets have shown strong preclinical activity in models of high cyclin E expression and CCNE1 amplification. Recent clinical trials have explored the efficacy and tolerability of these agents, particularly in biomarker selected cohorts. The WEE1 inhibitor adavosertib and the CDK2 inhibitor INCB123667 achieved response rates of 53 % and 33 % respectively in platinum-resistant ovarian cancer patients whose tumours overexpressed cyclin E1. Targeting of cyclin E dysregulation via a synthetic lethality approach is therefore a key area of focus for improving treatment strategies in HGSOC and other cancers with high unmet clinical need. In this review we discuss the functions of cyclin E1, mechanisms and consequences of dysregulation, and strategies for therapeutic exploitation of cyclin E1 dysregulated tumours, combining fundamental biology with clinical perspectives.

Cyclin E1是细胞周期动力学的关键介质，与CDK2复合物控制G1/S相变。细胞周期蛋白E1的过度表达可导致复制应激、DNA损伤和基因组不稳定性升高。这与肿瘤发生有关，并经常观察到泛癌；但在高级别浆液性卵巢癌（HGSOC）中尤为常见。HGSOC表现出以结构变异和不稳定性为主导的基因组景观，高达58%的病例中cyclin E1高表达，高达30%的病例中CCNE1扩增。因此，HGSOC代表了研究癌症中周期蛋白E失调的范例设置。cyclin E1肿瘤高表达的HGSOC患者，结合拷贝数扩增，生存率特别差。靶向CDK2、WEE1和PYMKT1以及其他细胞周期相关靶点的药物在高cyclin E表达和CCNE1扩增的模型中显示出很强的临床前活性。最近的临床试验探索了这些药物的疗效和耐受性，特别是在生物标志物选择的队列中。WEE1抑制剂adavosertib和CDK2抑制剂INCB123667在肿瘤过表达cyclin E1的铂耐药卵巢癌患者中分别实现了53%和33%的缓解率。因此，通过合成致死性方法靶向细胞周期蛋白E失调是改善HGSOC和其他临床需求未得到满足的癌症治疗策略的关键领域。在这篇综述中，我们将结合基础生物学和临床观点，讨论细胞周期蛋白E1的功能，细胞周期蛋白E1失调的机制和后果，以及细胞周期蛋白E1失调肿瘤的治疗策略。

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引用次数: 0

Pseudogenes in breast cancer pathogenesis and their clinical utility 假基因与乳腺癌发病机制及其临床应用。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-08 DOI: 10.1016/j.critrevonc.2025.105078

Isabel Kannampuzha , Farhad Ghasemi , Armen Parsyan

Breast cancer remains as one of the leading causes of mortality and morbidity among women worldwide, underscoring the need for a better understanding of breast cancer etiopathogenesis, effective new therapeutics and clinically actionable biomarkers. Pseudogenes, traditionally seen as nonfunctional sequences of DNA, are increasingly recognized to have important functions in physiology and disease, including in various cancers. Recently accumulating and expanding body of data has emphasized the potential role of pseudogenes in multiple aspects of breast cancer pathogenesis including their function as oncogenes or tumor suppressors to influence cellular proliferation, migration, invasion, apoptosis, angiogenesis, immune modulation, and maintenance of cancer stem cell properties. Moreover, expression of many pseudogenes has been shown to correlate with patient survival parameters and clinicopathologic characteristics of the tumor, making them excellent candidates as prognostic biomarkers. Pseudogene expression can also modulate responses of breast cancer to chemotherapeutic agents and antihormonal treatments, as well as radiotherapy, indicating their potential as treatment response biomarkers. Given their functions in breast cancer biology, pseudogenes can serve as novel targets for treatment. Here, the roles of pseudogenes in breast cancer are discussed in detail.

乳腺癌仍然是世界范围内妇女死亡和发病的主要原因之一，强调需要更好地了解乳腺癌的发病机制，有效的新疗法和临床可操作的生物标志物。假基因，传统上被认为是DNA的无功能序列，越来越多地认识到在生理和疾病，包括各种癌症中具有重要功能。最近越来越多的数据强调了假基因在乳腺癌发病机制的多个方面的潜在作用，包括它们作为癌基因或肿瘤抑制因子的功能，影响细胞增殖、迁移、侵袭、凋亡、血管生成、免疫调节和肿瘤干细胞特性的维持。此外，许多假基因的表达已被证明与患者生存参数和肿瘤的临床病理特征相关，使其成为预后生物标志物的优秀候选人。假基因表达还可以调节乳腺癌对化疗药物和抗激素治疗以及放疗的反应，这表明它们有可能成为治疗反应的生物标志物。鉴于假基因在乳腺癌生物学中的功能，它们可以作为新的治疗靶点。本文将详细讨论假基因在乳腺癌中的作用。

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引用次数: 0

High-grade gastro-entero-pancreatic neuroendocrine neoplasms: An overlooked population in interventional clinical trials. A systematic review 高级别胃肠胰神经内分泌肿瘤：介入性临床试验中被忽视的人群。系统回顾。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-08 DOI: 10.1016/j.critrevonc.2025.105074

Elettra Merola , Maria Pina Dore , Giovanni Mario Pes , Giuseppe Fanciulli

Background

High-grade gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs) are a heterogeneous group of tumors with poor prognosis, including grade 3 neuroendocrine tumors (NETs G3) and neuroendocrine carcinomas (NECs), which represent distinct entities with different clinical outcomes. Our aim was to systematically review the available clinical evidence on therapeutic strategies for sporadic, highly proliferative GEP-NENs. Methods: A systematic literature search was conducted using PubMed, Scopus, and Web of Science (last update: August 9, 2025). Endpoints included the evaluation of clinical outcomes from interventional trials and subgroup analysis comparing NET G3 with NEC. Results: A total of 2135 records were retrieved, with a final inclusion of 28 prospective trials (six randomized trials). Twelve trials exclusively enrolled NECs, one trial focused on NET G3, five provided NET G3/NEC subanalyses, ten included mixed populations without morphological stratification. Owing to the high risk of bias, a meta-analysis was not feasible. In NECs, the highest disease control was achieved with the CAPOXIRI–Bevacizumab regimen (disease control rate, DCR 78.9 %; median progression-free survival, PFS 18 months; overall survival, OS 30.5 months), but the cohort was small (n = 19) and toxicity substantial. Immunotherapy yielded disappointing results, either as monotherapy or in combination with a dual checkpoint blockade (median PFS: ∼2 months). Platinum-based chemotherapy proved poor for NET G3, whereas temozolomide/everolimus and peptide receptor radionuclide therapy offered clear benefits (DCR: 96.1 % and 70 %, respectively). Conclusions: High-grade GEP-NENs (particularly NET G3) remain an overlooked population in interventional studies. Progress in precision medicine requires the identification of molecular biomarkers to guide individualized therapy.

背景：高级别胃-肠-胰神经内分泌肿瘤（GEP-NENs）是一种异质性的预后不良肿瘤，包括3级神经内分泌肿瘤（NETs G3）和神经内分泌癌（NECs），它们代表不同的实体，临床结局不同。我们的目的是系统地回顾有关散发性、高增殖性GEP-NENs治疗策略的现有临床证据。方法：系统检索PubMed、Scopus和Web of Science（最后更新日期：2025年8月9日）的文献。终点包括介入试验的临床结果评估和比较NET G3与NEC的亚组分析。结果：共检索到2135条记录，最终纳入28项前瞻性试验（6项随机试验）。12项试验专门纳入NEC， 1项试验专注于NET G3, 5项试验提供NET G3/NEC亚分析，10项试验包括没有形态分层的混合群体。由于偏倚风险高，meta分析不可行。在NECs中，capoxii - bevacizumab方案达到了最高的疾病控制率（疾病控制率，DCR为78.9%；中位无进展生存期，PFS为18个月；总生存期，OS为30.5个月），但队列很小（n=19）且毒性很大。免疫治疗的结果令人失望，无论是单药治疗还是联合双检查点阻断（中位PFS: ~2个月）。以铂为基础的化疗对NET G3的疗效较差，而替莫唑胺/依维莫司和肽受体放射性核素治疗有明显的疗效（DCR分别为96.1%和70%）。结论：在介入性研究中，高级别GEP-NENs（特别是NET G3）仍然是一个被忽视的人群。精准医学的进步需要识别分子生物标志物来指导个体化治疗。

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引用次数: 0

Sex differences in immunotherapy plus chemotherapy: A systematic review and meta-analysis 免疫治疗加化疗的性别差异：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 : 2025-12-06 DOI: 10.1016/j.critrevonc.2025.105069

Salah Ameen Abdu , Wafa Ali Asaad , Muaadh Wdaan , Ning Li

Background

Sex-based differences in immune response and cancer biology may influence treatment outcomes with immunotherapy combinations. Comprehensive evidence regarding whether biological sex affects the efficacy of immune checkpoint inhibitor plus chemotherapy regimens remains incomplete.

Methods

Following PRISMA guidelines, we systematically searched five databases through May 2025 for randomized controlled trials comparing immune checkpoint inhibitors plus chemotherapy versus chemotherapy alone in any cancer type. We performed a comprehensive meta-analysis with sex-stratified survival data, subgroup analyses across cancer types and treatment regimens, meta-regression, interaction testing with false discovery rate correction, and publication bias assessment.

Results

Seventy-nine trials enrolling 50,046 patients (30,503 males, 19,543 females) met inclusion criteria. Combination therapy significantly improved survival in both sexes: overall survival hazard ratios were 0.76 (95 % CI 0.73–0.78) in males and 0.78 (95 % CI 0.75–0.81) in females, representing 24 % and 22 % mortality reductions, respectively. Progression-free survival improved by 39 % in males (HR 0.61, 95 % CI 0.57–0.64) and 34 % in females (HR 0.66, 95 % CI 0.62–0.70). Overlapping confidence intervals and formal interaction testing revealed no statistically significant sex-based differences across cancer types, immunotherapy agents, histological subtypes, or chemotherapy backbones.

Conclusions

Immune checkpoint inhibitors with chemotherapy provide significant and equivalent survival benefits for both male and female patients across cancer types. Treatment decisions should therefore be guided by tumor characteristics, not patient sex. These results support equitable treatment access and highlight the necessity for continued sex-stratified data reporting in clinical trials.

背景：基于性别的免疫反应和癌症生物学差异可能影响免疫治疗组合的治疗结果。关于生理性别是否影响免疫检查点抑制剂加化疗方案的疗效的综合证据仍不完整。方法：遵循PRISMA指南，我们系统地检索了截至2025年5月的5个数据库，以比较免疫检查点抑制剂加化疗与单独化疗在任何癌症类型中的随机对照试验。我们进行了一项综合荟萃分析，包括按性别分层的生存数据、跨癌症类型和治疗方案的亚组分析、荟萃回归、带错误发现率校正的相互作用检验和发表偏倚评估。结果：79项试验纳入50,046例患者（男性30,503例，女性19,543例）符合纳入标准。联合治疗显著提高了两性的生存率：男性的总生存风险比为0.76 (95% CI 0.73-0.78)，女性的总生存风险比为0.78 (95% CI 0.75-0.81)，分别代表死亡率降低24%和22%。无进展生存率男性提高39% (HR 0.61, 95% CI 0.57-0.64)，女性提高34% （HR 0.66, 95% CI 0.62-0.70）。重叠置信区间和正式的相互作用测试显示，在癌症类型、免疫治疗药物、组织学亚型或化疗骨干之间，没有统计学上显著的基于性别的差异。结论：免疫检查点抑制剂联合化疗对不同癌症类型的男性和女性患者提供了显著且相同的生存益处。因此，治疗决定应以肿瘤特征为指导，而不是患者的性别。这些结果支持公平获得治疗，并强调在临床试验中继续按性别分层报告数据的必要性。

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引用次数: 0

Targeting the CCL2/CCR2 axis in colorectal cancer: Immunopharmacological perspectives and therapeutic strategies 靶向CCL2/CCR2轴治疗结直肠癌免疫药理学观点和治疗策略。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-06 DOI: 10.1016/j.critrevonc.2025.105072

Fatemeh Hajibabaie , Navid Abedpoor , Bahareh Maleki , Maryam Boshtam , Nasim Shenavar , Ali Zarrabi , Mina Babakhani , Mehran Sharifi , Laleh Shariati , Ilnaz Rahimmanesh , Marco Cordani

Colorectal cancer, a significant contributor to cancer-related fatalities worldwide, develops due to the complex interaction between tumor cells and their immediate environment. CCL2, a type of chemokine, plays a significant role in colorectal cancer advancement through its impact on immune cell recruitment, inflammation, and metastasis. The receptor CCR2 mediates CCL2's function in directing the migration of tumor-associated macrophages (TAMs), which in turn promotes epithelial-mesenchymal transition (EMT), angiogenesis, and immune evasion. According to this narrative review, the CCL2/CCR2 axis plays a key role in both the tumor microenvironment and the metastasis of CRC. The study investigates the therapeutic possibilities of CCL2 targeting, alongside creative bioengineering methods such as siRNA and miRNA therapies, aptamers, small molecules, and CRISPR technologies. Thanks to recent developments in bioinformatics and molecular therapies, it's now possible to explore innovative strategies to block the CCL2/CCR2 pathway, potentially leading to better alternatives for treating colorectal cancer. The main focus of future studies should be on addressing therapeutic resistance, enhancing combination therapies, and identifying predictive biomarkers to enhance treatment efficacy and patient results. The study reveals complex molecular interactions regulated by CCL2, thus offering a foundation for innovative therapeutic approaches to colorectal cancer.

结直肠癌是全球癌症相关死亡的重要原因之一，其发展是由于肿瘤细胞与其周围环境之间复杂的相互作用。CCL2是一种趋化因子，通过影响免疫细胞募集、炎症和转移，在结直肠癌的进展中发挥重要作用。受体CCR2介导CCL2在指导肿瘤相关巨噬细胞（tam）迁移中的功能，从而促进上皮-间质转化（EMT）、血管生成和免疫逃逸。根据这篇叙述性综述，CCL2/CCR2轴在肿瘤微环境和CRC转移中都起着关键作用。该研究调查了CCL2靶向治疗的可能性，以及创造性的生物工程方法，如siRNA和miRNA疗法、适体、小分子和CRISPR技术。由于生物信息学和分子疗法的最新发展，现在有可能探索阻断CCL2/CCR2通路的创新策略，从而有可能为治疗结直肠癌提供更好的选择。未来研究的重点应该是解决治疗耐药性，加强联合治疗，并确定预测性生物标志物，以提高治疗疗效和患者结果。该研究揭示了CCL2调控的复杂分子相互作用，从而为创新结直肠癌治疗方法提供了基础。

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引用次数: 0

Aromatase inhibitors and medication-related osteonecrosis of the jaw: Friends, foes, or bystanders? 芳香酶抑制剂和药物相关的颌骨骨坏死：朋友，敌人，还是旁观者？

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-05 DOI: 10.1016/j.critrevonc.2025.105071

Soraia Macari , Jôice Dias Corrêa , Victor Zanetti Drumond , Breno Amaral Rocha , Paula Alves da Silva Rocha , Lucas Guimarães Abreu , François Côme Ferré , Benjamin P.J. Fournier , José Alcides Almeida de Arruda , Tarcília Aparecida Silva

Since the 1980s, aromatase inhibitors (AI) have been a cornerstone in the management of hormone receptor-positive breast cancer. However, because of their frequent co-prescription with antiresorptive agents, concerns have been raised regarding the potential contribution of AI to medication-related osteonecrosis of the jaw (MRONJ). We conducted a scoping review to investigate the possible association between AI use and MRONJ. Electronic searches were performed across five databases and supplemented with manual screening and gray literature. Observational studies and clinical trials were included. Fifty-four studies comprising 1,613,480 individuals (45,121 AI users) from 17 countries were analyzed. Most samples consisted of women with breast cancer/metastatic breast cancer in pre- and/or postmenopausal stages. Letrozole was the most frequently prescribed AI, followed by anastrozole and exemestane. MRONJ was reported in 43 studies, with 1147 cases among 45,121 AI users (2.5 % of AI users in the included samples), the majority of whom were concomitantly treated with zoledronic acid and/or denosumab. Three studies documented MRONJ in patients receiving AI monotherapy. Data demonstrate the difficulty of disentangling the effects of AI from those of antiresorptive therapy in MRONJ pathogenesis. Future research should consider AI as potential confounders in analytical studies to clarify their independent contribution, if any, to observed MRONJ occurrences.

自20世纪80年代以来，芳香化酶抑制剂（AI）已成为激素受体阳性乳腺癌治疗的基石。然而，由于它们经常与抗吸收药物共同使用，人们开始关注人工智能对药物相关性颌骨骨坏死（MRONJ）的潜在贡献。我们进行了范围审查，以调查人工智能使用与MRONJ之间可能存在的关联。在五个数据库中进行电子检索，并辅以人工筛选和灰色文献。包括观察性研究和临床试验。对来自17个国家的1613480人（45121名人工智能用户）的54项研究进行了分析。大多数样本由绝经前和/或绝经后阶段的乳腺癌/转移性乳腺癌患者组成。来曲唑是最常用的人工智能处方，其次是阿那曲唑和依西美坦。43项研究报告了MRONJ，在45121名人工智能使用者中有1147例（在所纳入样本中占人工智能使用者的2.5%），其中大多数人同时接受唑来膦酸和/或地诺单抗治疗。三项研究记录了接受人工智能单药治疗的患者的MRONJ。数据表明，在MRONJ发病机制中，很难将AI的作用与抗吸收治疗的作用区分开来。未来的研究应该考虑人工智能作为分析研究中的潜在混杂因素，以澄清它们对观察到的MRONJ发生的独立贡献（如果有的话）。

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引用次数: 0

The crosstalk between ferroptosis and the immune system in urological cancers: Mechanisms, prognostic value, and therapeutic implications 泌尿系统肿瘤中铁下垂与免疫系统之间的串扰：机制、预后价值和治疗意义。

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-05 DOI: 10.1016/j.critrevonc.2025.105070

Shuwen Li, Zeli Li

Ferroptosis—an iron-dependent, lipid peroxidation–driven cell death—has emerged as a central regulator of tumor biology and antitumor immunity in prostate, bladder, and renal cancers. Beyond direct cytotoxicity, it bidirectionally reshapes the tumor immune microenvironment. CD8 + and NK cells induce ferroptosis via IFN-γ–mediated suppression of system Xc−, whereas ferroptotic cells release DAMPs and antigens that mature dendritic cells and activate T cells. Conversely, ferroptosis in effector lymphocytes and tumor antioxidant, metabolic, and myeloid programs can enforce immune suppression. mRNA and lncRNA ferroptosis signatures stratify prognosis and immunotherapy response, often separating checkpoint-restrained “hot” tumors from immune-excluded/desert states. Mechanistic nodes (SLC7A11, GPX4, PRMT5, ATF4/NUPR1) and stromal/macrophage circuits link ferroptosis resistance to immune evasion. Emerging strategies combine ferroptosis induction with checkpoint blockade, adoptive cellular therapies, nano-delivery, and microenvironment reprogramming to convert “cold” disease into durable responders.

铁中毒是一种铁依赖性、脂质过氧化驱动的细胞死亡，已成为前列腺癌、膀胱癌和肾癌肿瘤生物学和抗肿瘤免疫的中心调节因子。除了直接的细胞毒性外，它还双向重塑肿瘤免疫微环境。CD8+和NK细胞通过IFN-γ介导的系统Xc-抑制诱导铁下垂，而铁下垂细胞释放DAMPs和抗原，使树突状细胞成熟并激活T细胞。相反，铁下垂在效应淋巴细胞和肿瘤抗氧化，代谢和骨髓程序可以加强免疫抑制。mRNA和lncRNA铁下垂特征对预后和免疫治疗反应进行分层，通常将检查点受限的“热”肿瘤与免疫排斥/沙漠状态区分开来。机制节点（SLC7A11, GPX4, PRMT5, ATF4/NUPR1）和基质/巨噬细胞回路将铁凋亡抵抗与免疫逃避联系起来。新兴的策略结合了铁死亡诱导与检查点阻断、过继细胞疗法、纳米递送和微环境重编程，将“冷”疾病转化为持久的应答。

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引用次数: 0

Adaptive drug resistance mechanisms driven by non-coding RNA–protein interaction networks in hepatocellular carcinoma 肝细胞癌非编码rna -蛋白相互作用网络驱动的适应性耐药机制

IF 5.6 2区医学 Q1 HEMATOLOGY

Critical reviews in oncology/hematology

Pub Date : 2025-12-05 DOI: 10.1016/j.critrevonc.2025.105060

Yu Tian , Kaobin Ouyang , Hongsheng Wu , Haojie Liao , Lingjuan He , Tingting Luo , Keqiang Ma , Xiaowen Mao , Furong Wang , Hailin Xiong

Hepatocellular carcinoma (HCC) remains a major cause of cancer mortality due to profound heterogeneity and persistent therapeutic resistance. This review summarizes recent mechanistic advances showing how noncoding RNAs (ncRNAs)—including lncRNAs and circRNAs—cooperate with RNA-binding proteins (RBPs) to regulate ferroptosis, autophagy, lipid metabolism, immune evasion, and transcriptional programs. We highlight emerging principles involving RNA chemical modifications, structural elements, and liquid–liquid phase separation that define the specificity of ncRNA–RBP interactions. Recent multi-omics and spatial profiling technologies are also discussed for their role in revealing resistance-associated ncRNA–protein networks. Importantly, this review integrates these findings to outline actionable therapeutic opportunities and the translational potential of targeting ncRNA–RBP axes, emphasizing their relevance to precision oncology. By defining the key regulatory circuits that drive adaptive resistance, this work provides a conceptual framework that may guide biomarker development and personalized treatment strategies in HCC.

由于严重的异质性和持续的治疗耐药性，肝细胞癌（HCC）仍然是癌症死亡的主要原因。本文综述了近年来非编码rna (ncRNAs)-包括lncRNAs和circrnas -如何与rna结合蛋白（rbp）协同调节铁死亡、自噬、脂质代谢、免疫逃避和转录程序的机制进展。我们强调涉及RNA化学修饰、结构元件和液-液相分离的新兴原理，这些原理定义了ncRNA-RBP相互作用的特异性。最近的多组学和空间分析技术也讨论了它们在揭示耐药相关的ncrna -蛋白网络中的作用。重要的是，本综述整合了这些发现，概述了可操作的治疗机会和靶向ncRNA-RBP轴的转化潜力，强调了它们与精确肿瘤学的相关性。通过定义驱动适应性抵抗的关键调控回路，这项工作提供了一个概念框架，可以指导HCC的生物标志物开发和个性化治疗策略。

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引用次数: 0