Biochimica et biophysica acta. Reviews on cancer最新文献_第10页

Colorectal cancer chemoprevention: Exploring the path from molecular mechanisms to available drugs 结直肠癌化学预防：探索从分子机制到可用药物的途径

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-09-02 DOI: 10.1016/j.bbcan.2025.189439

Devon M. Ivy, Rosa Bordone, Laura Di Magno, Sonia Coni, Gianluca Canettieri

Colorectal cancer (CRC) remains a significant global health challenge despite advances in screening and diagnostic modalities that have contributed to reduced incidence and mortality. A substantial proportion of cases, however, continue to be diagnosed at advanced stages. Chemoprevention – the use of natural or synthetic substances to prevent cancer initiation or recurrence - has emerged as a promising strategy, particularly for individuals at elevated risk. While several agents have shown clinical efficacy, the underlying mechanisms driving their protective effects are not yet fully understood. In this Review, we provide a comprehensive overview of the molecular pathogenesis of CRC and highlight key druggable targets relevant to chemoprevention, including inflammation, polyamine metabolism, mitochondrial function, epigenetic regulation, and promising new avenues targeting aspects such as the tumor microenvironment and the gut microbiota. We provide a significant contribution to the field by intersecting the established clinical and preclinical results to the growing understanding of chemopreventative mechanism of action, identifying potential for the stratification of patient risks and benefits among their molecular roles and side effects. Finally, based on the improved molecular understanding of CRC tumorigenesis, we propose potential new avenues of colorectal chemoprevention.

尽管筛查和诊断方式的进步有助于降低发病率和死亡率，但结直肠癌（CRC）仍然是一个重大的全球健康挑战。然而，很大一部分病例在晚期才被诊断出来。化学预防——使用天然或合成物质来预防癌症的发生或复发——已经成为一种很有前途的策略，特别是对高危人群而言。虽然一些药物已经显示出临床疗效，但驱动其保护作用的潜在机制尚未完全了解。在这篇综述中，我们全面概述了结直肠癌的分子发病机制，并强调了与化学预防相关的关键药物靶点，包括炎症、多胺代谢、线粒体功能、表观遗传调控，以及有前途的新途径，如肿瘤微环境和肠道微生物群。我们通过将已建立的临床和临床前结果与对化学预防作用机制的日益了解相结合，在其分子作用和副作用中确定患者风险和收益分层的潜力，为该领域做出了重大贡献。最后，基于对结直肠癌发生的分子认识的提高，我们提出了结直肠癌化学预防的潜在新途径。

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引用次数: 0

Testicular germ cell tumors and infertility: Exploring epigenetic dysregulation in the journey of the male germ cell towards new biomarkers and therapeutics 睾丸生殖细胞肿瘤和不孕症：探索男性生殖细胞向新的生物标志物和治疗的旅程中的表观遗传失调

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-09-01 DOI: 10.1016/j.bbcan.2025.189437

Bruno Oliveira-Lopes , Nuno Tiago Tavares , Rui Henrique , Carmen Jerónimo , João Lobo

The development of male germ cells comprises a series of differentiation events that culminate in the formation of spermatozoa. From the primordial germ cell (PGC) to the spermatid, an array of epigenetic events take place in different stages of life. Disruptions in these mechanisms due to external factors can ultimately lead to decreased fertility and to testicular germ cell tumors (TGCTs). In this review, we highlight how DNA methylation, histone modifications and non-coding RNAs (ncRNAs) contribute to normal male germ cell development and discuss how disturbances in this epigenetic machinery can compromise fertility and induce neoplasia. Furthermore, the bidirectional relationship between infertility and TGCTs is discussed. Finally, we disclose the utility of “epidrugs” and ncRNAs as promising therapeutic options and TGCT biomarkers, respectively.

男性生殖细胞的发育包括一系列分化事件，最终形成精子。从原始生殖细胞（PGC）到精细胞，一系列的表观遗传事件发生在生命的不同阶段。外部因素对这些机制的破坏最终会导致生育能力下降和睾丸生殖细胞肿瘤（tgct）。在这篇综述中，我们强调了DNA甲基化，组蛋白修饰和非编码rna （ncRNAs）如何促进正常的男性生殖细胞发育，并讨论了这种表观遗传机制的干扰如何损害生育能力和诱导肿瘤。此外，还讨论了不孕与tgct的双向关系。最后，我们分别揭示了“外药物”和ncrna作为有希望的治疗选择和TGCT生物标志物的效用。

引用次数: 0

Osteoblasts in bone metastasis: Key players in the tumor microenvironment and therapeutic targets 骨转移中的成骨细胞：肿瘤微环境和治疗靶点的关键参与者。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-29 DOI: 10.1016/j.bbcan.2025.189435

Lingxiao Jin , Zhenxuan Shao , Zhaoming Ye , Binghao Li

Osteoblasts, recognized for their role in bone formation and mineral metabolism, are emerging as pivotal, although underexplored, regulators within the bone tumor microenvironment (TME). Despite increasing evidence of their involvement, their precise contributions to metastatic progression remain underappreciated. Recent studies reveal that osteoblasts orchestrate metastasis through dynamic, stage-specific interactions. In early colonization, they may attract tumor cells via CXCL12/CXCR4 signaling and remodel the metastatic niche. During dormancy, osteoblast-derived factors such as LIF, TGFβ2, and BMP7, along with adhesion molecules such as N-cadherin, promote therapy resistance. Subsequently, osteoblasts can drive metastatic outgrowth through metabolic coupling (e.g., Ca²⁺ transfer) and mTOR pathway activation. Beyond these direct effects on tumor cells, osteoblasts modulate the TME by interacting with osteoclasts and immune cells, suppressing CD8⁺ T/NK cell activity while skewing macrophage polarization to promote immune evasion. Tumor-derived signals including PTHrP, BMPs, and ET-1, further reprogram osteoblasts into a tumor-supportive phenotype. Therapeutic approaches, such as RANKL inhibition, CXCL12 pathway blockade, TGF-β superfamily antagonism, and osteoblast-targeted immunotherapies, offer promising directions for clinical intervention. Recognizing osteoblasts as central players in bone metastasis may provide new frontiers in bone-targeted cancer therapy.

成骨细胞因其在骨形成和矿物质代谢中的作用而得到认可，虽然尚未得到充分的研究，但它们正在成为骨肿瘤微环境（TME）中的关键调节因子。尽管越来越多的证据表明它们的参与，但它们对转移进展的确切贡献仍未得到充分认识。最近的研究表明，成骨细胞通过动态的、阶段特异性的相互作用来协调转移。在早期定植中，它们可能通过CXCL12/CXCR4信号吸引肿瘤细胞并重塑转移生态位。在休眠期间，成骨细胞衍生因子如LIF、TGFβ2和BMP7，以及粘附分子如N-cadherin，促进治疗抵抗。随后，成骨细胞可以通过代谢偶联（如Ca2+转移）和mTOR通路激活来驱动转移性生长。除了这些对肿瘤细胞的直接作用外，成骨细胞还通过与破骨细胞和免疫细胞相互作用来调节TME，抑制CD8+ T/NK细胞活性，同时扭曲巨噬细胞极化以促进免疫逃避。肿瘤来源的信号包括PTHrP、bmp和ET-1，进一步将成骨细胞重编程为肿瘤支持表型。RANKL抑制、CXCL12通路阻断、TGF-β超家族拮抗、成骨细胞靶向免疫治疗等治疗方法为临床干预提供了有希望的方向。认识到成骨细胞在骨转移中的核心作用可能为骨靶向癌症治疗提供新的领域。

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引用次数: 0

Role of mesenchymal stem cells in modulating cytokine networks and immune checkpoints in gastric cancer therapy 间充质干细胞在胃癌治疗中调节细胞因子网络和免疫检查点的作用

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-29 DOI: 10.1016/j.bbcan.2025.189433

Zakari Shaibu , Isah Adamu Danbala , Zhihong Chen , Wei Zhu

Gastric cancer (GC) remains a leading cause of cancer-related mortality worldwide, driven by a complex tumor microenvironment (TME) that promotes disease progression and therapeutic resistance. This review explores the pivotal roles of mesenchymal stem cells (MSCs), cytokines, and immune checkpoint inhibitors (ICIs) in shaping the immunosuppressive GC TME, with emphasis on their interaction and implications for immunotherapy. MSCs secrete cytokines such as IL-6, TGF-β, and IL-10, fostering an immunosuppressive milieu that enables tumor growth, immune evasion, and resistance to ICIs. We synthesize current knowledge on how MSC-derived cytokines regulate immune checkpoint expression, suppress anti-tumor immunity, and contribute to TME heterogeneity. Additionally, we discuss therapeutic strategies targeting MSC-cytokine-immune checkpoint interactions to enhance ICI efficacy and improve clinical outcomes. Emerging approaches including MSC reprogramming, exosome-based therapies, and multi-omics technologies are highlighted as promising avenues to decipher TME complexity and develop personalized immunotherapies. By elucidating mechanisms of MSC-mediated immune modulation in GC, this review aims to inspire novel strategies to overcome therapeutic resistance in this challenging disease.

胃癌（GC）仍然是全球癌症相关死亡的主要原因，由促进疾病进展和治疗耐药性的复杂肿瘤微环境（TME）驱动。这篇综述探讨了间充质干细胞（MSCs）、细胞因子和免疫检查点抑制剂（ICIs）在形成免疫抑制性GC - TME中的关键作用，重点是它们的相互作用和免疫治疗的意义。MSCs分泌IL-6、TGF-β和IL-10等细胞因子，形成免疫抑制环境，促进肿瘤生长、免疫逃避和对ICIs的抵抗。我们综合了目前关于msc来源的细胞因子如何调节免疫检查点表达、抑制抗肿瘤免疫和促进TME异质性的知识。此外，我们还讨论了针对msc -细胞因子-免疫检查点相互作用的治疗策略，以提高ICI的疗效和改善临床结果。新兴的方法包括MSC重编程、基于外泌体的疗法和多组学技术被强调为破译TME复杂性和开发个性化免疫疗法的有希望的途径。通过阐明GC中msc介导的免疫调节机制，本综述旨在激发新的策略来克服这种具有挑战性的疾病的治疗耐药。

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引用次数: 0

Molecular mechanisms of TAM-regulated tumorigenesis and progression in various types of radiotherapy and future prospects of radiation-immunotherapy combinations tam在不同类型放疗中调控肿瘤发生和进展的分子机制以及放射-免疫联合治疗的未来前景

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-29 DOI: 10.1016/j.bbcan.2025.189434

Luyu Liao , Yuzhao Jin , Wei Mao , Ji Zhu , Qianping Chen

Although conventional photon radiotherapy can eradicate tumors, the presence of radioresistance has limited treatment efficacy. Nowadays the multiple radiotherapies carried out around different physics beam types will provide more options for tumor treatment. Under the current trend of anti-tumor immunotherapy, tumor-associated macrophages (TAMs), as an important component of the tumor microenvironment, significantly influence tumor progression and prognosis of comprehensive tumor therapy through reciprocal regulation with radiotherapy. The aim of this review is to summarize the influence of radiotherapy with various beam types on the biological effects of TAMs, and to explore the physiological basis for the conjunction of radiotherapy and immunotherapy based on TAMs. Ultimately, these data will provide an evidence-based medical rationale and translational research basis for optimizing the combination of radiotherapy and immunotherapy as a treatment modality for tumors in the future.

虽然传统的光子放射治疗可以根除肿瘤，但放射耐药的存在限制了治疗效果。目前，围绕不同物理光束类型进行的多种放射治疗为肿瘤治疗提供了更多的选择。在当前抗肿瘤免疫治疗的趋势下，肿瘤相关巨噬细胞（tumor-associated macrophages, tam）作为肿瘤微环境的重要组成部分，通过与放疗的相互调节，显著影响肿瘤综合治疗的肿瘤进展和预后。本文就不同光束类型的放疗对TAMs生物学效应的影响进行综述，探讨基于TAMs的放疗与免疫治疗结合的生理基础。最终，这些数据将为未来优化放疗与免疫治疗联合作为肿瘤治疗方式提供循证医学依据和转化研究依据。

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引用次数: 0

Unlocking the power of innate lymphoid cell plasticity in the tumor microenvironment: A revolutionary pathway for cancer immunotherapy 解锁肿瘤微环境中先天淋巴细胞可塑性的力量：癌症免疫治疗的革命性途径

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-26 DOI: 10.1016/j.bbcan.2025.189430

Peng Yin , Pei Cao , Yu Liang , Chao Wang , Yu Tian

Innate lymphoid cells (ILCs) are emerging as powerful players in the immune system, capable of dramatically influencing tumor immunity. Their extraordinary plasticity, which allows them to adapt to dynamic changes in the tumor microenvironment, positions them as a double-edged sword in cancer immunotherapy. While they can drive anti-tumor immune responses, they can also promote tumor progression under certain conditions. In this review, we delve into the multifaceted roles of ILCs—focusing on ILC1, ILC2, and ILC3—and explore how their functional plasticity can be harnessed to shift their activities from immune suppression to potent anti-tumor actions. We highlight groundbreaking therapeutic strategies aimed at modulating ILC plasticity, such as metabolic reprogramming, cytokine therapy, and CAR-ILC1 therapy, each designed to enhance the anti-tumor potential of these cells. Despite the immense promise, challenges remain, including immune suppression within the TME and the short-lived efficacy of cytokines. However, targeting ILC plasticity offers a transformative approach to overcome these hurdles, presenting an opportunity to personalize cancer treatment and create tailored immunotherapies that dynamically modulate the immune response. This review underscores the game-changing potential of ILC-based therapies and provides insights into the next generation of cancer immunotherapies that could revolutionize the fight against cancer.

先天淋巴样细胞（ILCs）在免疫系统中扮演着重要的角色，能够显著影响肿瘤免疫。它们非凡的可塑性使它们能够适应肿瘤微环境的动态变化，这使它们成为癌症免疫治疗中的一把双刃剑。虽然它们可以驱动抗肿瘤免疫反应，但在某些条件下它们也可以促进肿瘤的进展。在这篇综述中，我们深入研究了ilc的多方面作用，重点是ILC1， ILC2和ilc3，并探讨了如何利用它们的功能可塑性将它们的活性从免疫抑制转变为有效的抗肿瘤作用。我们重点介绍了旨在调节ILC可塑性的突破性治疗策略，如代谢重编程、细胞因子治疗和CAR-ILC1治疗，每一种治疗都旨在增强这些细胞的抗肿瘤潜力。尽管前景广阔，但挑战依然存在，包括TME内的免疫抑制和细胞因子的短期功效。然而，靶向ILC可塑性为克服这些障碍提供了一种变革性的方法，为个性化癌症治疗和创建动态调节免疫反应的量身定制的免疫疗法提供了机会。这篇综述强调了基于ilc的疗法改变游戏规则的潜力，并为下一代癌症免疫疗法提供了见解，这些疗法可能会彻底改变对抗癌症的斗争。

{"title":"Unlocking the power of innate lymphoid cell plasticity in the tumor microenvironment: A revolutionary pathway for cancer immunotherapy","authors":"Peng Yin , Pei Cao , Yu Liang , Chao Wang , Yu Tian","doi":"10.1016/j.bbcan.2025.189430","DOIUrl":"10.1016/j.bbcan.2025.189430","url":null,"abstract":"<div><div>Innate lymphoid cells (ILCs) are emerging as powerful players in the immune system, capable of dramatically influencing tumor immunity. Their extraordinary plasticity, which allows them to adapt to dynamic changes in the tumor microenvironment, positions them as a double-edged sword in cancer immunotherapy. While they can drive anti-tumor immune responses, they can also promote tumor progression under certain conditions. In this review, we delve into the multifaceted roles of ILCs—focusing on ILC1, ILC2, and ILC3—and explore how their functional plasticity can be harnessed to shift their activities from immune suppression to potent anti-tumor actions. We highlight groundbreaking therapeutic strategies aimed at modulating ILC plasticity, such as metabolic reprogramming, cytokine therapy, and CAR-ILC1 therapy, each designed to enhance the anti-tumor potential of these cells. Despite the immense promise, challenges remain, including immune suppression within the TME and the short-lived efficacy of cytokines. However, targeting ILC plasticity offers a transformative approach to overcome these hurdles, presenting an opportunity to personalize cancer treatment and create tailored immunotherapies that dynamically modulate the immune response. This review underscores the game-changing potential of ILC-based therapies and provides insights into the next generation of cancer immunotherapies that could revolutionize the fight against cancer.</div></div>","PeriodicalId":8782,"journal":{"name":"Biochimica et biophysica acta. Reviews on cancer","volume":"1880 5","pages":"Article 189430"},"PeriodicalIF":9.7,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Multidimensional technological advances in cervical cancer screening: From standardized processes to precision medicine 宫颈癌筛查的多维技术进步：从标准化流程到精准医学

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-25 DOI: 10.1016/j.bbcan.2025.189432

Xiang Li , Jiaxin Zheng , Chang Liu , Bo Liu , Danbo Wang

Cervical cancer is a common malignancy among women worldwide. To address this significant public health issue, the World Health Organization launched the “Eliminating Cervical Cancer” initiative. Effective screening of cervical cancer is crucial for reducing its morbidity and mortality. With continuous technological advancements, cervical cancer screening has evolved from traditional cytology and human papillomavirus (HPV) testing models to a new era of multidimensional, multilevel, and precise screening. This comprehensive review focuses on the core progress of screening technology in recent years, including the innovation of traditional screening methods, noninvasive optical imaging, molecular diagnosis from the perspective of precision medicine, and the deep integration and empowerment of artificial intelligence in the entire screening process. Cervical liquid-based cytology, combined with automated cell sorting technology and intelligent whole-slide image analysis, has achieved high-throughput identification of abnormal cells. The accuracy and specificity of HPV and multiomic biomarker detection technologies have significantly improved, providing a new basis for the accurate triage of patients with high-risk infections. Noninvasive cervical imaging technology already offers early identification of cervical precancerous lesions at the molecular level, combining ease of use with good patient acceptance. Notably, artificial intelligence technology is being integrated into multiple screening processes, leveraging horizontal integration and cross-platform capabilities in image recognition, risk assessment, auxiliary diagnosis, and automated testing processes, becoming a key driver of innovation in screening systems.

子宫颈癌是全世界妇女中常见的恶性肿瘤。为了解决这一重大的公共卫生问题，世界卫生组织发起了“消除宫颈癌”倡议。有效的子宫颈癌筛检对降低发病率和死亡率至关重要。随着技术的不断进步，宫颈癌筛查已经从传统的细胞学和人乳头瘤病毒（HPV）检测模式发展到多维、多层次、精准筛查的新时代。本文综合综述了近年来筛查技术的核心进展，包括传统筛查方法的创新、无创光学成像、精准医学视角下的分子诊断，以及人工智能在整个筛查过程中的深度融合与赋能。宫颈液基细胞学结合自动化细胞分选技术和智能全片图像分析，实现了异常细胞的高通量鉴定。HPV和多组生物标志物检测技术的准确性和特异性显著提高，为高危感染患者的准确分诊提供了新的依据。无创宫颈成像技术已经在分子水平上提供了宫颈癌前病变的早期识别，结合了易用性和良好的患者接受度。值得注意的是，人工智能技术正在融入多个筛查流程，利用图像识别、风险评估、辅助诊断和自动化测试流程的横向集成和跨平台能力，成为筛查系统创新的关键驱动力。

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引用次数: 0

Trogocytosis at crossroads: Navigating the duality in tumor-immune cell interactions Trogocytosis在十字路口：导航肿瘤免疫细胞相互作用的双重性。

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-25 DOI: 10.1016/j.bbcan.2025.189431

Xin Yang , Xiaolu Huang , Zhuonan Chen , Wei Zhang , Ousheng Liu , Jianjun Wu , Fei Yan

Trogocytosis, derived from the Greek “trogo-,” meaning “nibble,” is a cellular process in which one cell extracts membrane fragments and surface molecules from another, modulating the functions of both donor and recipient cells. In tumor immunology, trogocytosis between immune cells and tumor cells exhibits paradoxical effects. Conflicting reports suggest it can enhance antitumor effects through processes like trogoptosis, antigen presentation, and beneficial antigen shaving, while facilitating protumor effects by antigen masking, immune cell exhaustion, immune cell fratricide, and detrimental antigen shaving. In this review, we discuss recent insights in trogocytosis between immune cells (T cells, natural killer cells, neutrophils, monocytes/macrophages, chimeric antigen receptor cells, and antigen-presenting cells) and tumor cells, summarize the distinct interaction patterns and characteristics, and highlight its dual role in enhancing anti-tumor immunity and facilitating tumor immune evasion. Additionally, we explore the strategies to exploit trogocytosis in immunotherapy, aiming to deepen insights into immune-tumor interactions and to improve therapeutic outcomes.

Trogocytosis来源于希腊语“trogo-”，意思是“啃咬”，是一种细胞过程，一个细胞从另一个细胞中提取膜碎片和表面分子，调节供体细胞和受体细胞的功能。在肿瘤免疫学中，免疫细胞和肿瘤细胞之间的巨噬细胞现象表现出矛盾的效应。相互矛盾的报告表明，它可以通过诸如肌萎缩、抗原呈递和有益抗原剃除等过程增强抗肿瘤作用，同时通过抗原掩蔽、免疫细胞耗竭、免疫细胞自相残杀和有害抗原剃除等过程促进肿瘤作用。本文综述了近年来免疫细胞（T细胞、自然杀伤细胞、中性粒细胞、单核/巨噬细胞、嵌合抗原受体细胞和抗原呈递细胞）与肿瘤细胞之间的噬细胞作用，总结了其独特的相互作用模式和特征，并强调了其在增强抗肿瘤免疫和促进肿瘤免疫逃避方面的双重作用。此外，我们还探索了在免疫治疗中利用细胞增多症的策略，旨在加深对免疫-肿瘤相互作用的了解，并改善治疗结果。

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引用次数: 0

The dysregulated YY1-EZH2-RKIP axis in cancer cells and immune evasion 癌细胞中YY1-EZH2-RKIP轴失调与免疫逃避

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-21 DOI: 10.1016/j.bbcan.2025.189424

Talia Festekdjian, Benjamin Bonavida

We have recently witnessed several milestones in the treatment of a subset of cancer patients with immunotherapy and resulting in significant clinical responses. However, there is a subset that is unresponsive due to resistant factors in the cancer cells that are responsible for immune evasion. The characterization of such factors might lead to novel targeted therapies to restore the anti-tumor immunotherapies. We describe three dysregulated gene products, namely, Yin Yang1 (YY1), EZH2, and RKIP (PEBP1), that play pivotal roles in immune evasion. We report on the various molecular regulatory roles and signaling pathways that lead to the overexpression of YY1 and EZH2 and under expression of RKIP in cancer cells and established cross-talk signaling pathways amongst these three gene products. Such cross-talks established the dysregulated YY1-EZH2-RKIP axis and its pivotal role in the regulation of immune evasion. Thus, this axis is a potentially new therapeutic target to inhibit immune evasion by targeting the inhibition of YY1 or EZH2 or the induction of RKIP. Various agents are discussed to target each of these gene products, alone or in combination, to be investigated preclinically. However, the specific targeting to the tumor cells and sparing normal tissues is challenging, though new approaches are feasible.

我们最近见证了免疫疗法治疗一部分癌症患者的几个里程碑，并产生了显著的临床反应。然而，由于癌细胞中负责免疫逃避的耐药因素，有一部分是无反应的。这些因素的表征可能会导致新的靶向治疗，以恢复抗肿瘤免疫治疗。我们描述了三种失调的基因产物，即阴阳1 （YY1）、EZH2和RKIP (PEBP1)，它们在免疫逃避中起关键作用。我们报道了癌细胞中导致YY1和EZH2过表达和RKIP低表达的各种分子调控作用和信号通路，并建立了这三个基因产物之间的串音信号通路。这种交叉对话建立了失调的YY1-EZH2-RKIP轴及其在免疫逃避调节中的关键作用。因此，该轴是通过抑制YY1或EZH2或诱导RKIP来抑制免疫逃避的潜在新治疗靶点。讨论了针对这些基因产物的各种药物，单独或联合使用，以进行临床前研究。然而，尽管新方法是可行的，但特异性靶向肿瘤细胞并保留正常组织是具有挑战性的。

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引用次数: 0

Targeted drug delivery systems in Lymphoma treatment: Advances and clinical perspectives 淋巴瘤治疗中的靶向药物输送系统：进展和临床前景

IF 9.7 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Biochimica et biophysica acta. Reviews on cancer

Pub Date : 2025-08-21 DOI: 10.1016/j.bbcan.2025.189429

Qianqian Guo , Yingshu Luo , Xin Wang , Shunfeng Hu

Lymphomas are a heterogeneous group of hematologic tumors that pose a significant challenge in precise treatment. With the development of novel intervention strategies in lymphoma, such as targeted drugs and cell therapy, the prognosis and outcome of lymphoma patients have been greatly improved. However, there are also about 30 % of patients that display recurrence and eventually die, mainly due to the low effectiveness and targeting of current treatments. The advancements in novel drug delivery systems have revolutionized drug efficacy and tumor targeting in lymphoma treatment. Over the past few decades, various drug delivery systems, including nanocarriers, proteins, aptamers, and exosomes, have shown promising prospects in targeted therapy for lymphoma. These targeted delivery systems could carry anti-lymphoma drugs through physical embedding or chemical conjugation, which mitigate side effects and enhance therapeutic efficacy by ameliorating toxicity, prolonging systemic circulation time, and facilitating crossing of the blood-brain barrier. This review aims to summarize different drug delivery systems employed in lymphoma treatment and highlight their current applications and potential future implications, which might pave the way for the development of targeted therapy in lymphoma.

淋巴瘤是一种异质性的血液学肿瘤，对精确治疗提出了重大挑战。随着靶向药物和细胞治疗等新的淋巴瘤干预策略的发展，淋巴瘤患者的预后和转归得到了极大的改善。然而，也有大约30%的患者出现复发并最终死亡，这主要是由于目前治疗的有效性和靶向性较低。新型药物传递系统的进步已经彻底改变了淋巴瘤治疗的药物疗效和肿瘤靶向性。在过去的几十年里，各种药物递送系统，包括纳米载体、蛋白质、适体和外泌体，在淋巴瘤的靶向治疗中显示出良好的前景。这些靶向递送系统可以通过物理包埋或化学偶联的方式携带抗淋巴瘤药物，通过改善毒性、延长体循环时间、促进血脑屏障的通过，减轻副作用，提高治疗效果。本文综述了淋巴瘤治疗中不同的药物传递系统，并重点介绍了它们的应用现状和潜在的未来意义，以期为淋巴瘤靶向治疗的发展铺平道路。

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引用次数: 0