Seminars in oncology最新文献_第2页

Submicron silica particles drives prostate cancer aggressiveness via lipid-metabolic reprogramming 亚微米二氧化硅颗粒通过脂质代谢重编程驱动前列腺癌的侵袭性。

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2026-02-01 Epub Date: 2025-10-30 DOI: 10.1016/j.seminoncol.2025.152433

Pengpeng Su , Qianfeng Xu , Yan Wang , Wenjie Xie , Jundong Lin , Yangjia Zhuo , Jianheng Ye , Jianming Lu , Zhaodong Han , Fen Zou , Qishan Dai , Weide Zhong

Micron-sized (1 µm - 100 µm) and submicron-sized (100 nm–1 µm) silica particles are prevalent in both natural environments and areas influenced by human activities. Their environmental forms, origins, and pathways of human exposure differ markedly from those of nanoscale silica. Empirical studies have demonstrated that silica can induce cellular oxidative stress and mitochondrial dysfunction, as well as inhibit the activity of key enzymes in the tricarboxylic acid (TCA) cycle, such as isocitrate dehydrogenase. This inhibition can promote tumor cell proliferation and invasion. Furthermore, silica may activate the HIF-1α/mTOR signaling axis, leading to the upregulation of glucose transporter GLUT1 and lactate dehydrogenase (LDHA), thereby enhancing glycolytic metabolic flux. Concurrently, it may inhibit fatty acid β-oxidation, resulting in abnormal lipid accumulation and the promotion of pro-inflammatory mediator release. In summary, the accumulation of submicron silica within the bodies of cancer patients has the potential to induce metabolic disorders. Such metabolic reprogramming may influence the progression of prostate cancer (PCa) and adversely impact postoperative quality of life. In this study, we demonstrated that prolonged exposure of the lungs to submicron silica particles can induce alterations in lipid metabolism in PCa and significantly enhance the proliferation and invasive capacity of PCa cells. Consequently, elucidating the mechanisms underlying silica-induced metabolic imbalance holds substantial clinical significance for enhancing the prognosis of patients with tumors related to exposure.

微米尺寸（1微米- 100微米）和亚微米尺寸（100纳米-1微米）的二氧化硅颗粒普遍存在于自然环境和受人类活动影响的地区。它们的环境形式、来源和人类暴露途径与纳米级二氧化硅明显不同。实证研究表明，二氧化硅可以诱导细胞氧化应激和线粒体功能障碍，并抑制三羧酸（TCA）循环中关键酶的活性，如异柠檬酸脱氢酶。这种抑制作用可以促进肿瘤细胞的增殖和侵袭。此外，二氧化硅可能激活HIF-1α/mTOR信号轴，导致葡萄糖转运蛋白GLUT1和乳酸脱氢酶（LDHA）的上调，从而增强糖酵解代谢通量。同时，它可能抑制脂肪酸β-氧化，导致异常脂质积累，促进促炎介质释放。总之，亚微米二氧化硅在癌症患者体内的积累有可能诱发代谢紊乱。这种代谢重编程可能影响前列腺癌（PCa）的进展，并对术后生活质量产生不利影响。在这项研究中，我们证明了长时间暴露于亚微米二氧化硅颗粒的肺部可以诱导前列腺癌的脂质代谢改变，并显著增强前列腺癌细胞的增殖和侵袭能力。因此，阐明二氧化硅诱导的代谢失衡机制对于改善暴露相关肿瘤患者的预后具有重要的临床意义。

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引用次数: 0

UBE2T promotes papillary thyroid carcinoma progression by activating the JAK/STAT3 pathway via negative regulation of SOCS2 UBE2T通过负调控SOCS2激活JAK/STAT3通路，促进甲状腺乳头状癌的进展。

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2026-02-01 Epub Date: 2025-11-08 DOI: 10.1016/j.seminoncol.2025.152439

Lijun Zhang , Chengyuan Li , Jianing Zhou , Xiang Zhang , Haisheng Fang , Jingsheng Cai , Houchao Tong , Jianfei Wen , Heda Zhang , Meiping Shen , Yan Si

Papillary thyroid carcinoma (PTC) exhibits aggressive behaviors such as tumor invasion and lymph node metastasis that critically influence prognosis, yet reliable predictors of invasiveness remain elusive. This study investigated the molecular mechanisms through which ubiquitin-conjugating enzyme E2T (UBE2T) drives PTC progression. Bioinformatics analysis of TCGA/GEO datasets and validation with institutional clinical samples revealed UBE2T overexpression correlated with advanced clinicopathological features. Functional experiments demonstrated that UBE2T overexpression enhanced PTC cell invasiveness, while its knockdown suppressed malignant behaviors. Mechanistically, co-immunoprecipitation identified cytokine signaling suppressor 2 (SOCS2) as a key interactor mediating UBE2T's effects on JAK-STAT3 pathway activation. Rescue experiments and immunofluorescence confirmed UBE2T promotes oncogenesis by destabilizing SOCS2, thereby relieving its inhibition of STAT3 phosphorylation. These findings establish UBE2T as a novel regulator of PTC progression through SOCS2/JAK-STAT3 axis manipulation, providing potential therapeutic targets to mitigate metastasis and recurrence in aggressive thyroid carcinomas.

甲状腺乳头状癌（PTC）表现出侵袭性行为，如肿瘤侵袭和淋巴结转移，这对预后有重要影响，但侵袭性的可靠预测指标仍然难以捉摸。本研究探讨了泛素偶联酶E2T （UBE2T）驱动PTC进展的分子机制。TCGA/GEO数据集的生物信息学分析和机构临床样本验证显示，UBE2T过表达与晚期临床病理特征相关。功能实验表明，UBE2T过表达增强了PTC细胞的侵袭性，而UBE2T敲低则抑制了PTC细胞的恶性行为。在机制上，共免疫沉淀鉴定细胞因子信号抑制因子2 （SOCS2）是介导UBE2T对JAK-STAT3通路激活作用的关键相互作用因子。救援实验和免疫荧光证实，UBE2T通过破坏SOCS2的稳定促进肿瘤发生，从而减轻其对STAT3磷酸化的抑制。这些研究结果表明，UBE2T通过SOCS2/JAK-STAT3轴调控PTC进展，为减轻侵袭性甲状腺癌的转移和复发提供了潜在的治疗靶点。

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引用次数: 0

Genome editing of immune checkpoints: CRISPR-mediated PD-1 inhibition in cancer 免疫检查点的基因组编辑：crispr介导的PD-1在癌症中的抑制作用

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2026-02-01 Epub Date: 2025-11-04 DOI: 10.1016/j.seminoncol.2025.152438

SuleimanIbrahim Mohammad , A.K. Kareem , Asokan Vasudevan , MM Rekha , Majid S. Jabir , PriyaPriyadarshini Nayak , Zahraa AlKhafaje , Vimal Arora , WesamR Kadhum , Kattela Chennakesavulu

The programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint is a primary mechanism by which tumors evade immune surveillance, limiting the efficacy of cytotoxic T lymphocytes (CTLs) and tumor-infiltrating lymphocytes (TILs). Although immune checkpoint blockade therapies have revolutionized cancer treatment, their efficacy is restricted by acquired resistance, T-cell exhaustion, and tumor heterogeneity. The advent of CRISPR-Cas9 genome editing provides a precise and versatile approach to disrupt PD-1 or PD-L1, directly enhancing anti-tumor immune responses. Preclinical studies demonstrate that ex vivo PD-1 knockout in primary human T cells or TILs enhances proliferation, cytokine production, and cytotoxicity, resulting in improved tumor clearance in xenograft and humanized mouse models. In chimeric antigen receptor (CAR) T cell therapy, CRISPR-mediated disruption of PD-1 improves effector function, persistence, and resistance to exhaustion, with universal and allogeneic CAR-T platforms benefiting from multiplex genome editing. Direct PD-L1 knockout in tumor cells, often facilitated via nanoparticle- or biomaterial-assisted delivery, reshapes the immunosuppressive tumor microenvironment, promotes T cell infiltration, and enhances the efficacy of adoptive cellular therapy. Combination approaches integrating PD-1 editing with viral antigen targeting, long noncoding RNA (lncRNA) modulation, or conventional checkpoint blockade demonstrate synergistic anti-tumor effects. Clinically, early-phase trials in non-small cell lung cancer, mesothelin-positive solid tumors, and hematological malignancies establish the feasibility, safety, and preliminary efficacy of PD-1-deficient T cells. Despite these promising outcomes, challenges such as off-target effects, delivery efficiency, immunogenicity, long-term persistence, and regulatory considerations remain. This review aims to comprehensively evaluate preclinical and clinical studies investigating CRISPR-mediated PD-1/PD-L1 inhibition across various cancers, summarize mechanistic insights, and highlight translational opportunities and challenges for clinical implementation.

程序性细胞死亡蛋白1 (PD-1)/程序性死亡配体1 （PD-L1）免疫检查点是肿瘤逃避免疫监视的主要机制，限制了细胞毒性T淋巴细胞（ctl）和肿瘤浸润淋巴细胞（TILs）的功效。尽管免疫检查点阻断疗法已经彻底改变了癌症治疗，但其疗效受到获得性耐药、t细胞衰竭和肿瘤异质性的限制。CRISPR-Cas9基因组编辑的出现提供了一种精确和通用的方法来破坏PD-1或PD-L1，直接增强抗肿瘤免疫反应。临床前研究表明，在原代人T细胞或TILs中体外敲除PD-1可增强增殖、细胞因子产生和细胞毒性，从而提高异种移植和人源化小鼠模型的肿瘤清除率。在嵌合抗原受体（CAR） T细胞治疗中，crispr介导的PD-1破坏改善了效应器功能、持久性和抗衰竭性，通用和异体CAR-T平台受益于多重基因组编辑。在肿瘤细胞中直接敲除PD-L1，通常通过纳米颗粒或生物材料辅助递送，重塑免疫抑制的肿瘤微环境，促进T细胞浸润，并增强过继细胞治疗的疗效。将PD-1编辑与病毒抗原靶向、长链非编码RNA （lncRNA）调节或传统检查点阻断相结合的联合方法显示出协同抗肿瘤作用。临床上，在非小细胞肺癌、间皮素阳性实体瘤和血液系统恶性肿瘤中的早期试验证实了pd -1缺陷T细胞的可行性、安全性和初步疗效。尽管取得了这些有希望的结果，但诸如脱靶效应、给药效率、免疫原性、长期持久性和监管考虑等挑战仍然存在。本综述旨在全面评估研究crispr介导的PD-1/PD-L1抑制在各种癌症中的临床前和临床研究，总结机制见解，并强调临床实施的转化机遇和挑战。

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引用次数: 0

The nervous system in prostate cancer: A basic science and clinical perspective 前列腺癌的神经系统：基础科学和临床观点

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2026-02-01 Epub Date: 2025-10-24 DOI: 10.1016/j.seminoncol.2025.152425

Dawid Sigorski , Anna Kasprzyk-Pawelec , Maciej Michalak , Roman Sosnowski , Michał M. Hryciuk , Aleksandra Sejda , Jacek Gulczyński , Joanna Kitlinska , Sergiusz Nawrocki , Ewa Iżycka-Świeszewska

Prostate cancer (PCa) constitutes an important health challenge worldwide. The nervous system, in a complex and multimodal manner, regulates prostate physiology and PCa development and affects the course of the disease. The phenomena of axonogenesis and neurogenesis, first described in PCa, were a breakthrough discovery that changed our understanding of cancer-nerve crosstalk. Different nerve types within the cancer stroma and tumor surroundings create complex interactions between the cancer microenvironment elements based on neurotransmission, affecting the hallmarks of cancer. The most common form of PCa and nerve interaction is the perineural invasion (PNI), which recently has been suggested as a driver of metastases. Additionally, many preclinical discoveries depict the molecular mechanisms of altered nerve activity, showing the pivotal role of sympathetic and parasympathetic signaling systems in localized and advanced PCa, axon-guidance molecules and neurotrophin. The neuroendocrine switch in advanced PCa is one of reasons of lethal, castration-resistant phase of the disease. Knowledge about the infiltration status of the periprostatic nerves present in radiological imaging is important for urologists in planning the treatment. Although some studies suggest that PNI and nerve density may be prognostic factors in PCa, it is necessary to evaluate these indicators better and apply them to practice. The neural-based therapeutic application in PCa is limited currently. Some studies showed that β blockers reduce PCa-specific mortality and neuroendocrine differentiation potential. This review provides a comprehensive, up-to date synthesis of PCa neurobiology, uniquely integrating both preclinial and clinical perspectives.

前列腺癌（PCa）是世界范围内一个重要的健康挑战。神经系统以复杂和多模式的方式调节前列腺生理和前列腺癌的发展，并影响疾病的病程。在PCa中首次描述的轴突发生和神经发生现象是一个突破性的发现，改变了我们对癌症-神经串扰的理解。肿瘤基质和肿瘤环境中不同类型的神经在基于神经传递的癌症微环境元素之间产生复杂的相互作用，影响癌症的特征。前列腺癌与神经相互作用最常见的形式是神经周围浸润（PNI），最近被认为是转移的驱动因素。此外，许多临床前发现描述了神经活动改变的分子机制，显示了交感和副交感信号系统在局部和晚期PCa、轴突引导分子和神经营养蛋白中的关键作用。晚期前列腺癌的神经内分泌开关是该疾病致死性、去势抵抗期的原因之一。了解前列腺周围神经的浸润状况，在放射成像是重要的泌尿科医生在计划治疗。虽然一些研究表明PNI和神经密度可能是前列腺癌的预后因素，但有必要更好地评估这些指标并将其应用于实践。目前基于神经的治疗在PCa中的应用是有限的。一些研究表明β受体阻滞剂可降低pca特异性死亡率和神经内分泌分化潜能。这篇综述提供了一个全面的，最新的PCa神经生物学合成，独特地整合了临床前和临床的观点。

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引用次数: 0

CAR-T cell therapy: A therapeutic strategy for cancer treatment CAR-T细胞疗法：癌症治疗的一种治疗策略。

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1016/j.seminoncol.2025.152430

Shabana Sharif, Upma Sharma, Ashok Kumar Yadav

In the twenty-first century, chimeric antigen receptor (CAR)-T cell therapy has transformed cancer immunotherapy by offering novel approaches and life-saving treatments for illnesses that were previously incurable. This method is currently being used in clinical trials for solid tumors like prostate cancer and glioblastoma, as well as viral and autoimmune illnesses. It has demonstrated impressive efficacy in treating a variety of hematological malignancies. Harvesting a patient's T cells, genetically modifying them using viral vectors to express CARs that target specific antigens, and then reintroducing the altered cells into the patient is the process of CAR-T cell therapy. These CAR-T cells detect and destroy target cells specifically, regardless of the presence of the major histocompatibility complex (MHC) antigen. The major turning points in the development of CAR-T cells, from their creation to their use in medicine, are highlighted in this overview. It describes how CAR-T cells were developed historically, highlights the significant advancements that have made them a ground-breaking treatment, and talks about the obstacles that still need to be overcome, such as the high cost of production, restricted availability, and toxicity problems like cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. The review also looks at the field's future developments with the goals of increasing therapeutic uses, minimizing toxicity, and maximizing efficacy. With safer and more efficient CAR T cell therapies being developed, we are optimistic that a larger group of cancer patients may soon benefit from this innovative treatment.

在21世纪，嵌合抗原受体(CAR)-T细胞疗法通过为以前无法治愈的疾病提供新的方法和挽救生命的治疗方法，改变了癌症免疫疗法。这种方法目前被用于前列腺癌和胶质母细胞瘤等实体肿瘤的临床试验，以及病毒和自身免疫性疾病。它在治疗多种血液系统恶性肿瘤方面表现出令人印象深刻的疗效。获取患者的T细胞，用病毒载体对其进行基因修饰，使其表达针对特定抗原的car，然后将改变后的细胞重新引入患者体内，这就是CAR-T细胞疗法的过程。不管主要组织相容性复合体（MHC）抗原是否存在，这些CAR-T细胞特异性地检测和破坏靶细胞。本文概述了CAR-T细胞发展的主要转折点，从它们的产生到它们在医学上的应用。它描述了CAR-T细胞的历史发展过程，强调了使其成为突破性治疗方法的重大进展，并讨论了仍然需要克服的障碍，例如生产成本高，可用性有限，以及细胞因子释放综合征和免疫效应细胞相关神经毒性综合征等毒性问题。该综述还着眼于该领域的未来发展，目标是增加治疗用途，最小化毒性和最大化功效。随着更安全、更有效的CAR - T细胞疗法的开发，我们乐观地认为，更多的癌症患者可能很快就会从这种创新疗法中受益。

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引用次数: 0

Ubiquitin-specific proteases in pancreatic cancer: Molecular regulators of tumor progression and therapy resistance 胰腺癌中泛素特异性蛋白酶：肿瘤进展和治疗耐药性的分子调节因子。

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-12-01 Epub Date: 2025-09-16 DOI: 10.1016/j.seminoncol.2025.152410

Jitendra Gupta , Furqan N. Al-Khateeb , Ahmad Zwenal , Ali G. Alkhathami , Malathi H , Mayank Kundlas , Laxmidhar Maharana , Ashish Singh Chauhan , Yasser Fakri Mustafa , Mohammed Jawad Alnajar

Pancreatic cancer is caused by a complicated set of molecular changes that include genetic mutations and aberrant signaling pathways, which result in tumor growth, metastatic spread, and resistance to therapeutics. Of the various molecular changes, standard modifying processes, such as ubiquitination and deubiquitination, influence protein levels, cellular localization, and protein function. In this context, ubiquitin-specific proteases (USPs), a primary class of deubiquitinases (DUBs), play a crucial role in regulating the ubiquitin-proteasome system, which controls protein degradation and activity in cells. These USPs can cause the removal of ubiquitin from target proteins, thereby reversing the ubiquitination process. They are key for maintaining cellular homeostasis by regulating the turnover of proteins, including those responsible for signal transduction, cellular processes (such as the cell cycle), and the response to stress events. At the same time, USPs (including USP21, USP13, USP51, and USP22) also affect multiple signaling pathways, including the Wnt, NF-κB, and TGF-β pathways, all of which are involved in the biology of pancreatic cancer. USPs will promote or inhibit cancer-associated pathways that drive proliferation, metastasis, immune evasion, and therapy resistance by stabilizing or destabilizing specific signaling molecules. This review will examine the mechanistic roles of USPs in pancreatic cancer, as well as the tumor behavior and therapeutic resistance that may result from the dysregulation of these proteins. Ultimately, by presenting an opportunity to develop targeted therapies against specific USPs, we hope to emphasize new therapeutic strategies that could positively impact the lives of patients suffering from this aggressive disease.

胰腺癌是由一系列复杂的分子变化引起的，包括基因突变和异常的信号通路，导致肿瘤生长、转移扩散和对治疗药物的耐药性。在各种分子变化中，标准的修饰过程，如泛素化和去泛素化，影响蛋白质水平、细胞定位和蛋白质功能。在这种情况下，泛素特异性蛋白酶（USPs），一类主要的去泛素酶（DUBs），在调节泛素-蛋白酶体系统中起着至关重要的作用，该系统控制细胞中蛋白质的降解和活性。这些USPs可以导致泛素从靶蛋白中去除，从而逆转泛素化过程。它们是通过调节蛋白质的周转来维持细胞稳态的关键，包括那些负责信号转导、细胞过程（如细胞周期）和对应激事件的反应的蛋白质。同时，USPs（包括USP21、USP13、USP51、USP22）还影响多种信号通路，包括Wnt、NF-κB、TGF-β通路，这些通路均参与胰腺癌的生物学过程。USPs将通过稳定或破坏特定信号分子来促进或抑制驱动增殖、转移、免疫逃避和治疗抵抗的癌症相关途径。本文将探讨USPs在胰腺癌中的机制作用，以及这些蛋白失调可能导致的肿瘤行为和治疗耐药性。最终，通过提供针对特定USPs开发靶向治疗的机会，我们希望强调新的治疗策略，这些策略可以积极影响患有这种侵袭性疾病的患者的生活。

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引用次数: 0

Corrigendum to “Are we there yet? Gut microbiota for cancer diagnosis, prognosis and treatment” [Seminars in Oncology Volume 52, Issue 4, 2025, 152376] “Are we there yet?”肠道微生物群对癌症的诊断、预后和治疗”[肿瘤研讨会，第52卷，第4期，2025年，152376]。

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-12-01 Epub Date: 2025-11-06 DOI: 10.1016/j.seminoncol.2025.152432

Carlos Ordóñez , Sara Zurita , Giuliana Ramírez , Fernanda Cordeiro , Katherine Garcia-Matamoros , Fuad Huaman-Garaicoa , Andrea Orellana-Manzano , Lorena Sandoya-Onofre , Juan Roca-Pogo , Diana Carvajal-Aldaz

引用次数: 0

Tumor tough, therapy smarter: Rethinking CAR-T for pancreatic cancer 肿瘤难治，治疗更聪明：重新思考CAR-T治疗胰腺癌

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-12-01 Epub Date: 2025-09-04 DOI: 10.1016/j.seminoncol.2025.152411

Daniel A. Guirguis , Fariha Hasan , Natalie Morris , Andrew Alabd , Paula Mortada Shehata Tawfik , Kartick Pramanik , Manoj K Pandey

Chimeric antigen receptor (CAR) T-cell therapy has changed how we treat blood cancers but hasn't worked as well for solid tumors like pancreatic ductal adenocarcinoma (PDAC), mainly because these tumors are very aggressive and resistant to regular treatments. This review critically examines peer-reviewed studies to chart the evolution of immunotherapy in PDAC, emphasizing the unique barriers to effective CAR T-cell treatment and emerging strategies to overcome them. CAR T-cells that focus on tumor-related markers like mesothelin, HER2, and MUC1 have shown promise in early research models. However, clinical translation is hampered by obstacles such as a dense desmoplastic stroma that restricts T-cell infiltration, antigenic heterogeneity that promotes immune escape, and adverse effects including cytokine release syndrome. Recent innovations include dual-antigen targeting CARs (eg, CEA/MSLN), metabolic reprogramming to enhance T-cell function in nutrient-deprived tumor microenvironments, and stromal-targeting approaches such as fibroblast activation protein (FAP)-specific CARs and heparanase overexpression. Safety enhancements - such as reversible CAR inhibition using Dasatinib and GM-CSF neutralization - are also being explored to mitigate toxicity. Collectively, these advances represent promising strides toward enhancing the efficacy and safety of CAR T-cell therapy for pancreatic cancer. Ongoing research continues to identify new strategies to further refine these therapies, including the exploration of combination treatments with checkpoint inhibitors and novel immunomodulatory agents. As our understanding of the tumor microenvironment deepens, the potential for personalized approaches to CAR T-cell therapy may unlock even greater therapeutic benefits for patients.

嵌合抗原受体（CAR） t细胞疗法已经改变了我们治疗血癌的方式，但对胰腺导管腺癌（PDAC）等实体肿瘤的治疗效果并不好，主要是因为这些肿瘤具有很强的侵袭性，对常规治疗具有耐药性。本综述对同行评审的研究进行了严格的审查，以描绘PDAC免疫治疗的发展，强调了有效CAR - t细胞治疗的独特障碍和克服这些障碍的新策略。CAR - t细胞专注于肿瘤相关标志物，如间皮素、HER2和MUC1，在早期研究模型中显示出前景。然而，临床翻译受到一些障碍的阻碍，如限制t细胞浸润的致密结缔组织增生基质，促进免疫逃逸的抗原异质性，以及包括细胞因子释放综合征在内的不良反应。最近的创新包括双抗原靶向car（如CEA/MSLN），代谢重编程以增强营养缺乏的肿瘤微环境中的t细胞功能，以及基质靶向方法，如成纤维细胞活化蛋白（FAP）特异性car和肝素酶过表达。安全性增强——例如使用达沙替尼和GM-CSF中和的可逆CAR抑制——也正在探索以减轻毒性。总的来说，这些进展代表着在提高CAR - t细胞治疗胰腺癌的有效性和安全性方面取得了有希望的进展。正在进行的研究继续确定新的策略来进一步完善这些疗法，包括探索与检查点抑制剂和新型免疫调节剂的联合治疗。随着我们对肿瘤微环境理解的加深，CAR - t细胞治疗个性化方法的潜力可能会为患者带来更大的治疗益处。

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引用次数: 0

Metabolism at the core of melanoma: From bioenergetics to immune escape and beyond 黑色素瘤的核心代谢：从生物能量学到免疫逃逸及其他

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-12-01 Epub Date: 2025-09-12 DOI: 10.1016/j.seminoncol.2025.152413

Chou-Yi Hsu , Yasmeen Kateb Ahmed , Shaker mohammed , Mohammad A. Alghamdi , Hasan S. AL-Ghamdi , Jaafaru Sani Mohammed , Mohammed Abed Jawad , Salim B. Alsaadi

Melanoma is a particularly aggressive type of skin cancer due to its rapid growth and capacity to metastasize. There is substantial metabolic reprogramming in melanoma that is linked to its malignant characteristics, including therapeutic resistance. This review intended to provide a detailed overview of the central metabolic pathways reprogrammed in melanoma, including the Warburg effect and the complex interactions between glycolysis and oxidative phosphorylation, which ultimately influence energy production, biosynthesis, and adaptation to the tumor microenvironment. We also discuss the molecular pathways that regulate these metabolic pathways and the effect these metabolic processes have on crucial elements of melanoma progression, including invasion, metastasis, and survival during nutrient deprivation and hypoxia. Furthermore, we discuss the importance of metabolism beyond glucose, including glutamine metabolism, changes in lipid metabolism, and alterations in one-carbon and nucleotide biosynthesis, as well as mechanisms critical for the proliferation and survival of melanoma cells. An emphasis is placed on the active metabolic crosstalk between melanoma cells and the immune system within the tumor microenvironment, where melanoma cells utilize nutrient competition and the production of immunosuppressive metabolites to alter and block the function of anti-tumor immune cells, thereby facilitating immune evasion and therapy resistance. Lastly, we critically assess developments targeting melanoma metabolism, including pharmacological inhibition of key metabolic enzymes and pathways, as well as metabolic modulation to enhance the efficacy of conventional and immunotherapies. Although promising, this area is complex and subject to contextual effects and metabolic heterogeneity, indicating that we still have a way to go in annotating robust and clinically relevant metabolic targets. We sought to consolidate current knowledge about melanoma metabolism and highlight the challenges, future directions, and complexity of a potential therapeutic vulnerability in the rapidly evolving field of cancer research.

黑色素瘤是一种特别具有侵袭性的皮肤癌，因为它的快速生长和转移能力。在黑色素瘤中有大量的代谢重编程，这与它的恶性特征有关，包括治疗耐药性。这篇综述旨在提供黑色素瘤重编程的中心代谢途径的详细概述，包括Warburg效应和糖酵解和氧化磷酸化之间的复杂相互作用，最终影响能量产生、生物合成和对肿瘤微环境的适应。我们还讨论了调节这些代谢途径的分子途径，以及这些代谢过程对黑色素瘤进展的关键因素的影响，包括营养剥夺和缺氧时的侵袭、转移和存活。此外，我们还讨论了葡萄糖以外代谢的重要性，包括谷氨酰胺代谢、脂质代谢的变化、单碳和核苷酸生物合成的改变，以及黑色素瘤细胞增殖和存活的关键机制。重点放在肿瘤微环境中黑色素瘤细胞与免疫系统之间的主动代谢串扰，黑色素瘤细胞利用营养竞争和产生免疫抑制代谢物来改变和阻断抗肿瘤免疫细胞的功能，从而促进免疫逃避和治疗抵抗。最后，我们批判性地评估了针对黑色素瘤代谢的发展，包括关键代谢酶和途径的药理抑制，以及代谢调节，以提高常规和免疫疗法的疗效。尽管前景光明，但这一领域很复杂，容易受到环境效应和代谢异质性的影响，这表明我们在注释稳健且临床相关的代谢靶点方面仍有一段路要走。我们试图巩固目前关于黑色素瘤代谢的知识，并强调在快速发展的癌症研究领域中潜在治疗脆弱性的挑战、未来方向和复杂性。

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引用次数: 0

Application of single-layer continuous duct-to-mucosa pancreaticojejunostomy in oncologic pancreaticoduodenectomy 单层连续胰-黏膜胰空肠吻合术在肿瘤胰十二指肠切除术中的应用

IF 2.5 3区医学 Q2 ONCOLOGY

Seminars in oncology

Pub Date : 2025-12-01 Epub Date: 2025-09-11 DOI: 10.1016/j.seminoncol.2025.152415

Qun Chen , Fengyuan Liu , Lingtao Yan , Xumin Huang , Jishu Wei , Feng Guo , Jianmin Chen , Zipeng Lu , Junli Wu , Jie Yin , Pengfei Wu , Kuirong Jiang

Pancreaticojejunostomy is a critical step in pancreaticoduodenectomy, and its failure often results in pancreatic fistula. Clinically relevant pancreatic fistula (CRPF) can cause severe complications. This study evaluates the safety and feasibility of single-layer continuous duct-to-mucosa (SCD) pancreaticojejunostomy in preventing CRPF. We prospectively collected baseline characteristics and perioperative data from patients who underwent SCD pancreaticojejunostomy at our center between January and December 2020. A total of 156 patients were included in this study. The mean pancreaticojejunostomy time was 6.5 min, and the mean operation time was 247.6 min. CRPF occurred in 31 patients (19.9%), severe complications (Clavien-Dindo classification ≥III) occurred in 27 patients (17.3%), the mean length of hospitalization was 17.2 days, and the 90-days mortality was 0.0%. SCD pancreaticojejunostomy is an efficient and straightforward technique. It is applicable to various pancreatic conditions and demonstrates favorable clinical outcomes.

胰空肠吻合术是胰十二指肠切除术的关键步骤，其失败常导致胰瘘。临床相关胰瘘（CRPF）可引起严重的并发症。本研究评价单层连续胰空肠管粘膜吻合术预防CRPF的安全性和可行性。我们前瞻性地收集了2020年1月至12月在我们中心接受SCD胰空肠吻合术的患者的基线特征和围手术期数据。本研究共纳入156例患者。平均胰空肠吻合时间为6.5 min，平均手术时间为247.6 min。发生CRPF 31例（19.9%），严重并发症（Clavien-Dindo分级≥III） 27例（17.3%），平均住院时间17.2天，90天死亡率0.0%。SCD胰空肠吻合术是一种简单有效的技术。它适用于各种胰腺疾病，并具有良好的临床效果。

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