Seminars in cancer biology最新文献_第8页

The complex interplay of lipoprotein(a) and cancer in the era of emerging therapeutics 在新兴疗法时代，脂蛋白(a)与癌症的复杂相互作用。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-26 DOI: 10.1016/j.semcancer.2025.09.008

Vanessa Bianconi , Massimo R. Mannarino , Filippo Figorilli , Matteo Pirro , Amirhossein Sahebkar

In the last decades, the biological properties of Lp(a) have attracted increasing attention for their possible involvement in a wide range of clinical conditions other than atherosclerotic cardiovascular disease. To date, whether a pathogenic interplay may exist between Lp(a) and cancer remains unclear. Indeed, experimental studies mainly show a protective effect of Lp(a) toward cancer, while results of clinical studies are highly contradictory. Nonetheless, the confirmation of any link between Lp(a) metabolism and cancer may be highly impactful for its translational implications in the current era of a renewed scientific interest in this lipoprotein. Indeed, the increasing availability of laboratory assays for the routine assessment of plasma Lp(a) levels could be proposed as an additional tool for cancer diagnosis and prognostic stratification. In addition, the tumultuous development of anti-Lp(a) therapeutics, if a pro-cancerogenic Lp(a) activity will be confirmed, could have an impact on the natural history of cancer and on its pharmacological management. This review resumes current knowledge on the relationship between Lp(a) and cancer as well as on its possible impact on the oncological field.

在过去的几十年里，Lp(a)的生物学特性引起了越来越多的关注，因为它们可能与动脉粥样硬化性心血管疾病以外的广泛临床疾病有关。迄今为止，Lp(a)与癌症之间是否存在致病性相互作用仍不清楚。的确，实验研究主要显示了Lp(a)对癌症的保护作用，而临床研究结果却高度矛盾。尽管如此，在当前对这种脂蛋白重新产生科学兴趣的时代，证实Lp(a)代谢与癌症之间的任何联系可能对其翻译意义具有重大影响。的确，血浆Lp(a)水平常规评估的实验室检测方法越来越多，可以作为癌症诊断和预后分层的额外工具。此外，抗Lp(a)疗法的混乱发展，如果证实了促癌的Lp(a)活性，可能会对癌症的自然历史及其药理管理产生影响。本文综述了目前关于Lp(a)与癌症之间关系的知识，以及它在肿瘤学领域可能产生的影响。

{"title":"The complex interplay of lipoprotein(a) and cancer in the era of emerging therapeutics","authors":"Vanessa Bianconi , Massimo R. Mannarino , Filippo Figorilli , Matteo Pirro , Amirhossein Sahebkar","doi":"10.1016/j.semcancer.2025.09.008","DOIUrl":"10.1016/j.semcancer.2025.09.008","url":null,"abstract":"<div><div>In the last decades, the biological properties of Lp(a) have attracted increasing attention for their possible involvement in a wide range of clinical conditions other than atherosclerotic cardiovascular disease. To date, whether a pathogenic interplay may exist between Lp(a) and cancer remains unclear. Indeed, experimental studies mainly show a protective effect of Lp(a) toward cancer, while results of clinical studies are highly contradictory. Nonetheless, the confirmation of any link between Lp(a) metabolism and cancer may be highly impactful for its translational implications in the current era of a renewed scientific interest in this lipoprotein. Indeed, the increasing availability of laboratory assays for the routine assessment of plasma Lp(a) levels could be proposed as an additional tool for cancer diagnosis and prognostic stratification. In addition, the tumultuous development of anti-Lp(a) therapeutics, if a pro-cancerogenic Lp(a) activity will be confirmed, could have an impact on the natural history of cancer and on its pharmacological management. This review resumes current knowledge on the relationship between Lp(a) and cancer as well as on its possible impact on the oncological field.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 96-107"},"PeriodicalIF":15.7,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145186713","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

Lipid-laden macrophages in atherosclerosis and cancer 脂质巨噬细胞在动脉粥样硬化和癌症中的作用。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-24 DOI: 10.1016/j.semcancer.2025.09.007

MC Martinez-Campanario , Marlies Cortés , Lu Han , Agnese Brischetto , Paloma Rivero-Soriano , Joan Font-Díaz , Joan Maurel , Vicente Andrés , Antonio Postigo

This review explores the dual roles of lipid-laden macrophages (LL-Macs) in inflammation, atherosclerosis and cancer, emphasizing both their shared and divergent functions across physiological and pathological conditions. Lipid metabolism regulates the polarization of macrophages in homeostasis and inflammation. In atherosclerosis, LL-Macs contribute to plaque formation and inflammation, while in cancer, LL-Macs play crucial roles in immune suppression and tumor progression. The article outlines the molecular mechanisms driving macrophage lipid accumulation in each of these scenarios and how the process is influenced by the distinct local microenvironments in inflammation, atherosclerosis and cancer. Single-cell RNA sequencing (scRNA-seq) studies have identified both common and unique gene signatures between LL-Macs in atherosclerosis and cancer, reflecting the varying microenvironmental cues that shape macrophage function and disease outcomes. Finally, we examine lipid-modulating strategies in atherosclerosis, assess their potential in cancer treatment, and highlight research gaps for developing new LL-Macs targeted therapies in cancer.

本文探讨了脂质巨噬细胞（LL-Macs）在炎症、动脉粥样硬化和癌症中的双重作用，强调了它们在生理和病理条件下的共同和不同功能。脂质代谢调节巨噬细胞在稳态和炎症中的极化。在动脉粥样硬化中，ll - mac参与斑块形成和炎症，而在癌症中，ll - mac在免疫抑制和肿瘤进展中发挥重要作用。本文概述了在每种情况下驱动巨噬细胞脂质积累的分子机制，以及炎症、动脉粥样硬化和癌症中不同的局部微环境如何影响这一过程。单细胞RNA测序（scRNA-seq）研究已经确定了动脉粥样硬化和癌症中ll - mac之间共同和独特的基因特征，反映了塑造巨噬细胞功能和疾病结局的不同微环境线索。最后，我们研究了动脉粥样硬化中的脂质调节策略，评估了它们在癌症治疗中的潜力，并强调了开发新的ll - tam靶向治疗的研究空白。

{"title":"Lipid-laden macrophages in atherosclerosis and cancer","authors":"MC Martinez-Campanario , Marlies Cortés , Lu Han , Agnese Brischetto , Paloma Rivero-Soriano , Joan Font-Díaz , Joan Maurel , Vicente Andrés , Antonio Postigo","doi":"10.1016/j.semcancer.2025.09.007","DOIUrl":"10.1016/j.semcancer.2025.09.007","url":null,"abstract":"<div><div>This review explores the dual roles of lipid-laden macrophages (LL-Macs) in inflammation, atherosclerosis and cancer, emphasizing both their shared and divergent functions across physiological and pathological conditions. Lipid metabolism regulates the polarization of macrophages in homeostasis and inflammation. In atherosclerosis, LL-Macs contribute to plaque formation and inflammation, while in cancer, LL-Macs play crucial roles in immune suppression and tumor progression. The article outlines the molecular mechanisms driving macrophage lipid accumulation in each of these scenarios and how the process is influenced by the distinct local microenvironments in inflammation, atherosclerosis and cancer. Single-cell RNA sequencing (scRNA-seq) studies have identified both common and unique gene signatures between LL-Macs in atherosclerosis and cancer, reflecting the varying microenvironmental cues that shape macrophage function and disease outcomes. Finally, we examine lipid-modulating strategies in atherosclerosis, assess their potential in cancer treatment, and highlight research gaps for developing new LL-Macs targeted therapies in cancer.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"117 ","pages":"Pages 38-56"},"PeriodicalIF":15.7,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145177796","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

Molecular mechanisms and therapies of immune checkpoint inhibitor associated myocarditis: Update on recent developments 免疫检查点抑制剂相关心肌炎的分子机制和治疗：最新进展

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-23 DOI: 10.1016/j.semcancer.2025.09.006

Jiaqi Li, Lin Chen, Xiaolin Liu, Mei Zhang, Xiaoling Liu

Immune checkpoint inhibitors (ICIs) enhance systemic antitumor immune responses by improving the ability of immune cells to recognize and kill tumor cells specifically. Activated T lymphocytes may target tissues and organs outside the tumor, leading to different degrees of immune-related adverse events (irAEs). Immune checkpoint inhibitor-associated myocarditis (ICIAM) is a rare irAE, with an incidence of approximately 0.04–1.7 %. However, it is the most fatal irAE and often becomes a critical cause of short-term mortality in patients. Currently, the molecular mechanisms of ICIAM involve immune damage mediated by T-cell and macrophage infiltration, the common antigen theory, and pro-inflammatory responses driven by inflammatory factors and signaling pathways. However, the specific mechanisms remain unclear. A comprehensive understanding of the pathophysiological mechanisms of ICIAM can aid in identifying biomarkers and treatment targets for irAEs, ultimately improving the survival status of patients with cancer.

免疫检查点抑制剂（ICIs）通过提高免疫细胞特异性识别和杀伤肿瘤细胞的能力来增强全身抗肿瘤免疫应答。活化的T淋巴细胞可靶向肿瘤外的组织和器官，导致不同程度的免疫相关不良事件（irAEs）。免疫检查点抑制剂相关性心肌炎（ICIAM）是一种罕见的心肌炎，发病率约为0.04% ~ 1.7%。然而，它是最致命的irAE，经常成为患者短期死亡的关键原因。目前，ICIAM的分子机制包括t细胞和巨噬细胞浸润介导的免疫损伤、共同抗原理论、炎症因子和信号通路驱动的促炎反应。然而，具体机制尚不清楚。全面了解ICIAM的病理生理机制有助于确定irAEs的生物标志物和治疗靶点，最终提高癌症患者的生存状态。

引用次数: 0

Impaired cholesterol and LDL uptake pathways in the development of oncological and cardiovascular diseases 肿瘤和心血管疾病发展中的胆固醇和LDL摄取途径受损

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-23 DOI: 10.1016/j.semcancer.2025.09.004

Àngels Solanelles Curco , Eduardo Garcia , Anna Polishchuk , Maria Teresa La chica-Lhoëst , Vicenta Llorente-Cortes

Dietary lipids play a critical role in the development of cardiovascular disease and cancer by influencing key cellular processes. Lipoprotein and fatty acid receptors activate intracellular signaling pathways that promote tumor growth and vascular remodeling. A key event in both cancer and vascular diseases is the retention of low-density lipoproteins (LDL) and other lipoprotein particles by proteoglycans in the extracellular matrix (ECM) of atherosclerotic plaques and the tumor stroma. This retention facilitates lipoprotein modification processes. Dysregulated uptake of modified lipoproteins—particularly through receptors that are not downregulated by intracellular cholesterol levels—leads to excessive lipid accumulation within lipid droplets (LDs) and other intracellular organelles. The lipid and protein content of LDs and mitochondria determine the biophysical and functional characteristics of the crucial interactions between these suborgalles. In particular, lipid-derived mediators such as prostaglandins, leukotrienes, ceramides, oxidized fatty acids, and cholesterol can disrupt LD biogenesis and dynamics, impair mitochondrial function, and alter the expression, activity, and subcellular localization of proteins that regulate LD-mitochondria interactions. Dysfunctional communication between LDs and mitochondria contributes to the onset and progression of cancer and cardiovascular disease by disturbing cellular metabolism and energy homeostasis. Common LDL-related mechanisms in atherosclerosis and cancer have been summarized in Figure 1.

膳食脂类通过影响关键的细胞过程，在心血管疾病和癌症的发展中发挥关键作用。脂蛋白和脂肪酸受体激活细胞内信号通路，促进肿瘤生长和血管重塑。癌症和血管疾病的一个关键事件是低密度脂蛋白（LDL）和其他脂蛋白颗粒被蛋白聚糖滞留在动脉粥样硬化斑块和肿瘤基质的细胞外基质（ECM）中。这种保留有助于脂蛋白修饰过程。对修饰脂蛋白的摄取失调——特别是通过不受细胞内胆固醇水平下调的受体——导致脂滴（ld）和其他细胞内细胞器内过度的脂质积累。ld和线粒体的脂质和蛋白质含量决定了这些亚微粒之间关键相互作用的生物物理和功能特征。特别是，脂质来源的介质，如前列腺素、白三烯、神经酰胺、氧化脂肪酸和胆固醇可以破坏LD的生物发生和动力学，损害线粒体功能，并改变调节LD-线粒体相互作用的蛋白质的表达、活性和亚细胞定位。ld和线粒体之间功能失调的通信通过扰乱细胞代谢和能量稳态，有助于癌症和心血管疾病的发生和进展。

{"title":"Impaired cholesterol and LDL uptake pathways in the development of oncological and cardiovascular diseases","authors":"Àngels Solanelles Curco , Eduardo Garcia , Anna Polishchuk , Maria Teresa La chica-Lhoëst , Vicenta Llorente-Cortes","doi":"10.1016/j.semcancer.2025.09.004","DOIUrl":"10.1016/j.semcancer.2025.09.004","url":null,"abstract":"<div><div>Dietary lipids play a critical role in the development of cardiovascular disease and cancer by influencing key cellular processes. Lipoprotein and fatty acid receptors activate intracellular signaling pathways that promote tumor growth and vascular remodeling. A key event in both cancer and vascular diseases is the retention of low-density lipoproteins (LDL) and other lipoprotein particles by proteoglycans in the extracellular matrix (ECM) of atherosclerotic plaques and the tumor stroma. This retention facilitates lipoprotein modification processes. Dysregulated uptake of modified lipoproteins—particularly through receptors that are not downregulated by intracellular cholesterol levels—leads to excessive lipid accumulation within lipid droplets (LDs) and other intracellular organelles. The lipid and protein content of LDs and mitochondria determine the biophysical and functional characteristics of the crucial interactions between these suborgalles. In particular, lipid-derived mediators such as prostaglandins, leukotrienes, ceramides, oxidized fatty acids, and cholesterol can disrupt LD biogenesis and dynamics, impair mitochondrial function, and alter the expression, activity, and subcellular localization of proteins that regulate LD-mitochondria interactions. Dysfunctional communication between LDs and mitochondria contributes to the onset and progression of cancer and cardiovascular disease by disturbing cellular metabolism and energy homeostasis. Common LDL-related mechanisms in atherosclerosis and cancer have been summarized in Figure 1.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 84-95"},"PeriodicalIF":15.7,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145150579","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

Microorganisms in cancer tertiary lymphoid structure formation 微生物在癌症三级淋巴结构形成中的作用。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-19 DOI: 10.1016/j.semcancer.2025.09.005

Hao Li , Fei-Yang Chen , Qing Wang , Tian-Fu Wu , Zhi-Jun Sun

Tertiary lymphoid structures (TLSs) are essential in cancer immunotherapy, markedly improving the efficacy of immune checkpoint blockade (ICB) therapy. The presence of TLSs within the tumor microenvironment (TME) is associated with improved responses to ICB therapy, making them valuable biomarkers for predicting the efficacy of ICB therapy. Recent studies have demonstrated that diverse microorganisms—including bacteria, viruses, and eukaryotes such as fungi—impact the effectiveness of ICB treatments. Notably, studies also emphasize that specific microorganisms contribute to the development of TLSs. However, the interactions between microorganisms and TLSs are complex, and the specific mechanisms by which microorganisms impact TLS formation remain largely unknown. This review summarizes emerging advances on the formation processes of TLSs, focusing on the involved signaling pathways, and discusses how microorganisms facilitate TLS formation by affecting these pathways, chemokines, antigen presentation, and immune cells. Understanding these relationships could help in identifying microorganisms, chemokines, and signaling pathways as diagnostic or prognostic biomarkers in cancer, as well as new therapeutic approaches and potential targets for cancer treatment.

三级淋巴样结构（TLSs）在癌症免疫治疗中是必不可少的，它显著提高了免疫检查点阻断（ICB）治疗的疗效。肿瘤微环境（TME）中TLSs的存在与ICB治疗反应的改善有关，使其成为预测ICB治疗疗效的有价值的生物标志物。最近的研究表明，包括细菌、病毒和真核生物（如真菌）在内的多种微生物会影响ICB治疗的有效性。值得注意的是，研究还强调特定的微生物有助于tls的发展。然而，微生物与TLS之间的相互作用是复杂的，微生物影响TLS形成的具体机制在很大程度上仍然未知。本文综述了TLS形成过程的最新进展，重点介绍了涉及的信号通路，并讨论了微生物如何通过影响这些通路、趋化因子、抗原呈递和免疫细胞来促进TLS的形成。了解这些关系有助于确定微生物、趋化因子和信号通路作为癌症的诊断或预后生物标志物，以及新的治疗方法和癌症治疗的潜在靶点。

{"title":"Microorganisms in cancer tertiary lymphoid structure formation","authors":"Hao Li , Fei-Yang Chen , Qing Wang , Tian-Fu Wu , Zhi-Jun Sun","doi":"10.1016/j.semcancer.2025.09.005","DOIUrl":"10.1016/j.semcancer.2025.09.005","url":null,"abstract":"<div><div>Tertiary lymphoid structures (TLSs) are essential in cancer immunotherapy, markedly improving the efficacy of immune checkpoint blockade (ICB) therapy. The presence of TLSs within the tumor microenvironment (TME) is associated with improved responses to ICB therapy, making them valuable biomarkers for predicting the efficacy of ICB therapy. Recent studies have demonstrated that diverse microorganisms—including bacteria, viruses, and eukaryotes such as fungi—impact the effectiveness of ICB treatments. Notably, studies also emphasize that specific microorganisms contribute to the development of TLSs. However, the interactions between microorganisms and TLSs are complex, and the specific mechanisms by which microorganisms impact TLS formation remain largely unknown. This review summarizes emerging advances on the formation processes of TLSs, focusing on the involved signaling pathways, and discusses how microorganisms facilitate TLS formation by affecting these pathways, chemokines, antigen presentation, and immune cells. Understanding these relationships could help in identifying microorganisms, chemokines, and signaling pathways as diagnostic or prognostic biomarkers in cancer, as well as new therapeutic approaches and potential targets for cancer treatment.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 69-83"},"PeriodicalIF":15.7,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114058","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

Extracellular vesicles and the lipid messengers: The adipose tissue connection to cancer and metabolic disease. 细胞外囊泡和脂质信使：脂肪组织与癌症和代谢疾病的联系。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-18 DOI: 10.1016/j.semcancer.2025.09.003

Belen Picatoste , Heidy M. Guaman , Marina Herrero-Matesanz , Laura V. Piñeres , Alberto Benito-Martin

Adipose tissue is essential for maintaining metabolic balance by serving as a major lipid depot for energy storage and release, while also secreting adipokines and extracellular vesicles that regulate inflammation and insulin sensitivity. The lipidic content of adipose tissue not only supports energy homeostasis but also contributes to its inflammatory profile, with altered lipid composition being a key factor in the pathogenesis of metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disorders. Moreover, adipose tissue-derived extracellular vesicles, enriched in lipids, have emerged as significant mediators of intercellular communication, influencing local and systemic processes, including tumor progression. Adipose tissue-derived extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication, with increasing evidences describing their role in microenvironment communication. In this review, we explore the diverse lipid species identified within EVs and examine lipidomics as a powerful and emerging technique to decode their functional roles. By analyzing the lipid cargo of these vesicles, we highlight their potential influence on cancer progression and cardiovascular disease. Furthermore, we discuss the broader implications of EV-derived lipids in metabolic regulation and disease pathophysiology. Understanding the complex interplay between EV lipid composition and pathological processes could open new avenues for biomarker discovery and therapeutic interventions in oncology and cardiovascular medicine.

脂肪组织是维持代谢平衡所必需的，作为能量储存和释放的主要脂质仓库，同时也分泌脂肪因子和调节炎症和胰岛素敏感性的细胞外囊泡。脂肪组织的脂质含量不仅支持能量稳态，而且有助于其炎症谱，脂质组成的改变是代谢性疾病（如肥胖、2型糖尿病和心血管疾病）发病的关键因素。此外，脂肪组织来源的细胞外囊泡富含脂质，已成为细胞间通讯的重要介质，影响局部和全身过程，包括肿瘤进展。脂肪组织来源的细胞外囊泡（EVs）已成为细胞间通讯的关键介质，越来越多的证据描述了它们在微环境通讯中的作用。在这篇综述中，我们探讨了在ev中发现的多种脂质物种，并研究了脂质组学作为一种强大的新兴技术来解码它们的功能作用。通过分析这些囊泡的脂质货物，我们强调了它们对癌症进展和心血管疾病的潜在影响。此外，我们还讨论了ev衍生的脂质在代谢调节和疾病病理生理学中的广泛意义。了解EV脂质组成与病理过程之间的复杂相互作用可以为肿瘤和心血管医学的生物标志物发现和治疗干预开辟新的途径。

{"title":"Extracellular vesicles and the lipid messengers: The adipose tissue connection to cancer and metabolic disease.","authors":"Belen Picatoste , Heidy M. Guaman , Marina Herrero-Matesanz , Laura V. Piñeres , Alberto Benito-Martin","doi":"10.1016/j.semcancer.2025.09.003","DOIUrl":"10.1016/j.semcancer.2025.09.003","url":null,"abstract":"<div><div>Adipose tissue is essential for maintaining metabolic balance by serving as a major lipid depot for energy storage and release, while also secreting adipokines and extracellular vesicles that regulate inflammation and insulin sensitivity. The lipidic content of adipose tissue not only supports energy homeostasis but also contributes to its inflammatory profile, with altered lipid composition being a key factor in the pathogenesis of metabolic diseases such as obesity, type 2 diabetes, and cardiovascular disorders. Moreover, adipose tissue-derived extracellular vesicles, enriched in lipids, have emerged as significant mediators of intercellular communication, influencing local and systemic processes, including tumor progression. Adipose tissue-derived extracellular vesicles (EVs) have emerged as pivotal mediators of intercellular communication, with increasing evidences describing their role in microenvironment communication. In this review, we explore the diverse lipid species identified within EVs and examine lipidomics as a powerful and emerging technique to decode their functional roles. By analyzing the lipid cargo of these vesicles, we highlight their potential influence on cancer progression and cardiovascular disease. Furthermore, we discuss the broader implications of EV-derived lipids in metabolic regulation and disease pathophysiology. Understanding the complex interplay between EV lipid composition and pathological processes could open new avenues for biomarker discovery and therapeutic interventions in oncology and cardiovascular medicine.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 59-68"},"PeriodicalIF":15.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102977","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

Bile acids in liver and gastrointestinal cancer 胆汁酸在肝脏和胃肠道癌症中的作用。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-10 DOI: 10.1016/j.semcancer.2025.09.002

Maria J. Monte , Laura Fàbrega , Marta R. Romero , Alvaro G. Temprano , Neil Kaplowitz , Carmen Garcia-Ruiz , Jose J.G. Marin , Jose C. Fernandez-Checa

Bile acids (BAs) are cholesterol-derived metabolites synthesized by hepatocytes and secreted in bile to follow an inter-organ transit to the intestine, where they facilitate fat digestion and the absorption of lipids and liposoluble vitamins. Traditionally considered mere end products of cholesterol catabolism, they are now acknowledged to play intricate roles in regulating intermediary metabolism by controlling the expression of crucial genes. Additionally, they exert a significant impact on inflammation, cytotoxicity, and carcinogenesis. Moreover, BAs have a critical impact on the crosstalk between gut microbiota and host physiology, which affects the progression of liver and gastrointestinal cancers. Clinical data and results from studies of animal models support the involvement of BAs in the development of hepatocellular carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, and pancreatic cancer. On the other hand, BAs and their derivatives have been proposed as pharmacological tools in strategies to restore abnormal hepatobiliary function and target cytostatic agents to cancers of the enterohepatic circuit. In the present review, we summarize basic concepts of BA physiology and regulation, as well as new advances in this expanding field of renewed interest for cancer biology, lending further support for the key role of BAs in liver and gastrointestinal cancer.

胆汁酸（BAs）是由肝细胞合成的胆固醇衍生代谢物，在胆汁中分泌，在器官间转运到肠道，促进脂肪消化和脂质和脂溶性维生素的吸收。传统上认为它们只是胆固醇分解代谢的最终产物，现在人们认识到它们通过控制关键基因的表达在调节中间代谢中起着复杂的作用。此外，它们对炎症、细胞毒性和致癌作用有重要影响。此外，ba对肠道微生物群与宿主生理之间的串扰具有重要影响，从而影响肝脏和胃肠道癌症的进展。动物模型研究的临床数据和结果支持BAs参与肝细胞癌、胆管癌、结直肠腺癌和胰腺癌的发展。另一方面，BAs及其衍生物已被提出作为恢复肝胆功能异常和靶向细胞抑制剂治疗肠肝回路癌症的药理学工具。在本文中，我们总结了BA生理和调控的基本概念，以及这一不断扩大的癌症生物学领域的新进展，进一步支持BA在肝脏和胃肠道癌症中的关键作用。

{"title":"Bile acids in liver and gastrointestinal cancer","authors":"Maria J. Monte , Laura Fàbrega , Marta R. Romero , Alvaro G. Temprano , Neil Kaplowitz , Carmen Garcia-Ruiz , Jose J.G. Marin , Jose C. Fernandez-Checa","doi":"10.1016/j.semcancer.2025.09.002","DOIUrl":"10.1016/j.semcancer.2025.09.002","url":null,"abstract":"<div><div>Bile acids (BAs) are cholesterol-derived metabolites synthesized by hepatocytes and secreted in bile to follow an inter-organ transit to the intestine, where they facilitate fat digestion and the absorption of lipids and liposoluble vitamins. Traditionally considered mere end products of cholesterol catabolism, they are now acknowledged to play intricate roles in regulating intermediary metabolism by controlling the expression of crucial genes. Additionally, they exert a significant impact on inflammation, cytotoxicity, and carcinogenesis. Moreover, BAs have a critical impact on the crosstalk between gut microbiota and host physiology, which affects the progression of liver and gastrointestinal cancers. Clinical data and results from studies of animal models support the involvement of BAs in the development of hepatocellular carcinoma, cholangiocarcinoma, colorectal adenocarcinoma, and pancreatic cancer. On the other hand, BAs and their derivatives have been proposed as pharmacological tools in strategies to restore abnormal hepatobiliary function and target cytostatic agents to cancers of the enterohepatic circuit. In the present review, we summarize basic concepts of BA physiology and regulation, as well as new advances in this expanding field of renewed interest for cancer biology, lending further support for the key role of BAs in liver and gastrointestinal cancer.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 45-58"},"PeriodicalIF":15.7,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041200","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

Therapeutic pancreatic cancer biomarkers and pharmacogenetics 治疗性胰腺癌生物标志物和药物遗传学。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-06 DOI: 10.1016/j.semcancer.2025.08.002

Ales Langer , Pavel Soucek , Veronika Vymetalkova , Cosmeri Rizzato , Stefania Bunduc , Ilias P. Nikas , Viktor Hlavac , Michal Kroupa , Riccardo Farinella , Daniele Campa , Beatrice Mohelnikova-Duchonova

FOLFIRINOX and gemcitabine plus nab-paclitaxel represent the most effective chemotherapy regimens for metastatic pancreatic cancer patients nowadays, but the median overall survival remains less than one year. Pharmacogenomics and the individualization of therapy represent a promising strategy, including identifying patients at increased risk of toxicity. This review summarizes contemporary knowledge about genetic variability and putative biomarkers with published associations to therapy responses of pancreatic cancer not only for gold standard treatment regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel and nal-IRI/5-fluorouracil) but also for other therapeutic options regarding targeted therapy and immunotherapy. From the published data reviewed, it is evident that the problem is highly complex, and the ultimate profile of the drug-sensitive or resistant patient, followed by individualized therapy, is the most probable way to improve the poor prognosis of pancreatic cancer patients. Additionally, we will give a brief recap of what has been learned from genome-wide association studies, from gene candidate studies carried out in the context of large consortia such as the Pancreatic Disease Research (PANDoRA) consortium, and from studies focused on specific mutations in DNA repair genes.

FOLFIRINOX和吉西他滨加nab-紫杉醇是目前转移性胰腺癌患者最有效的化疗方案，但中位总生存期仍不到一年。药物基因组学和个体化治疗是一种很有前途的策略，包括识别毒性风险增加的患者。这篇综述总结了目前关于胰腺癌治疗反应的遗传变异和推测的生物标志物的知识，这些生物标志物不仅与金标准治疗方案（FOLFIRINOX、吉西他滨/nab-紫杉醇和nal-IRI/5-氟尿嘧啶）有关，而且与靶向治疗和免疫治疗有关。从已发表的资料来看，很明显，这个问题是高度复杂的，对药物敏感或耐药患者进行最终分析，然后进行个体化治疗，是改善胰腺癌患者不良预后的最有可能的方法。此外，我们将简要回顾从全基因组关联研究、在胰腺疾病研究（PANDoRA）等大型财团背景下进行的基因候选研究以及专注于DNA修复基因特定突变的研究中所学到的知识。

{"title":"Therapeutic pancreatic cancer biomarkers and pharmacogenetics","authors":"Ales Langer , Pavel Soucek , Veronika Vymetalkova , Cosmeri Rizzato , Stefania Bunduc , Ilias P. Nikas , Viktor Hlavac , Michal Kroupa , Riccardo Farinella , Daniele Campa , Beatrice Mohelnikova-Duchonova","doi":"10.1016/j.semcancer.2025.08.002","DOIUrl":"10.1016/j.semcancer.2025.08.002","url":null,"abstract":"<div><div>FOLFIRINOX and gemcitabine plus nab-paclitaxel represent the most effective chemotherapy regimens for metastatic pancreatic cancer patients nowadays, but the median overall survival remains less than one year. Pharmacogenomics and the individualization of therapy represent a promising strategy, including identifying patients at increased risk of toxicity. This review summarizes contemporary knowledge about genetic variability and putative biomarkers with published associations to therapy responses of pancreatic cancer not only for gold standard treatment regimens (FOLFIRINOX, gemcitabine/nab-paclitaxel and nal-IRI/5-fluorouracil) but also for other therapeutic options regarding targeted therapy and immunotherapy. From the published data reviewed, it is evident that the problem is highly complex, and the ultimate profile of the drug-sensitive or resistant patient, followed by individualized therapy, is the most probable way to improve the poor prognosis of pancreatic cancer patients. Additionally, we will give a brief recap of what has been learned from genome-wide association studies, from gene candidate studies carried out in the context of large consortia such as the Pancreatic Disease Research (PANDoRA) consortium, and from studies focused on specific mutations in DNA repair genes.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 31-44"},"PeriodicalIF":15.7,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145024155","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

Ketogenic diets: Dietary therapeutic potential on breast cancer 生酮饮食：饮食治疗乳腺癌的潜力。

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-05 DOI: 10.1016/j.semcancer.2025.09.001

Giuseppe Annunziata , Massimiliano Caprio , Evelyn Frias-Toral , Annamaria Colao , Luigi Barrea

Among the various types of tumors, breast cancer (BC) has a high distribution in the world population and is responsible for a high mortality rate. Like other forms of cancer, BC is characterised by distinctive features such as high-energy metabolism in tumor cells, genetic mutations, and mitochondrial dysfunction that sometimes make conventional therapies less effective. However, there is a growing awareness of the vital role played by diet therapy in the overall management of the patient with BC, both by supporting standard therapy and by directly targeting aberrant biological processes involved in carcinogenesis. Among the various nutritional strategies, the ketogenic diet (KD) has recently emerged as a promising therapeutic option for BC. Emerging evidence shows that KD, whether used alone or in combination with standard care, can directly influence tumor cell metabolism and reduces the risk of metastasis, thereby enhancing the efficacy of conventional drug therapies. This may allow for drug dose optimization, leading to fewer side effects and improved patient's quality of life. Nonetheless, the lack of clear evidence on the nutritional protocol to be adopted in BC patients, underlines the need for further research. This review aims to provide an overview of the effects of KD in the management of BC, both as a nutritional treatment and as an adjuvant therapy, providing insights into the implementation of precision nutrition protocols for this and other types of cancer.

在各种类型的肿瘤中，乳腺癌在世界人口中分布高，死亡率高。与其他形式的癌症一样，BC具有独特的特征，如肿瘤细胞的高能量代谢、基因突变和线粒体功能障碍，这些特征有时会使常规治疗效果降低。然而，越来越多的人意识到饮食疗法在BC患者的整体管理中所起的重要作用，无论是通过支持标准疗法还是直接针对致癌过程中涉及的异常生物过程。在各种营养策略中，生酮饮食（KD）最近成为一种有前途的治疗BC的选择。新的证据表明，无论是单独使用还是与标准治疗联合使用，KD都可以直接影响肿瘤细胞代谢，降低转移风险，从而提高常规药物治疗的疗效。这可能允许药物剂量优化，导致更少的副作用和提高患者的生活质量。尽管如此，缺乏明确的证据表明在BC患者中采用的营养方案强调了进一步研究的必要性。本综述旨在概述KD作为一种营养治疗和辅助治疗在BC治疗中的作用，为这种和其他类型癌症的精确营养方案的实施提供见解。

{"title":"Ketogenic diets: Dietary therapeutic potential on breast cancer","authors":"Giuseppe Annunziata , Massimiliano Caprio , Evelyn Frias-Toral , Annamaria Colao , Luigi Barrea","doi":"10.1016/j.semcancer.2025.09.001","DOIUrl":"10.1016/j.semcancer.2025.09.001","url":null,"abstract":"<div><div>Among the various types of tumors, breast cancer (BC) has a high distribution in the world population and is responsible for a high mortality rate. Like other forms of cancer, BC is characterised by distinctive features such as high-energy metabolism in tumor cells, genetic mutations, and mitochondrial dysfunction that sometimes make conventional therapies less effective. However, there is a growing awareness of the vital role played by diet therapy in the overall management of the patient with BC, both by supporting standard therapy and by directly targeting aberrant biological processes involved in carcinogenesis. Among the various nutritional strategies, the ketogenic diet (KD) has recently emerged as a promising therapeutic option for BC. Emerging evidence shows that KD, whether used alone or in combination with standard care, can directly influence tumor cell metabolism and reduces the risk of metastasis, thereby enhancing the efficacy of conventional drug therapies. This may allow for drug dose optimization, leading to fewer side effects and improved patient's quality of life. Nonetheless, the lack of clear evidence on the nutritional protocol to be adopted in BC patients, underlines the need for further research. This review aims to provide an overview of the effects of KD in the management of BC, both as a nutritional treatment and as an adjuvant therapy, providing insights into the implementation of precision nutrition protocols for this and other types of cancer.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 22-30"},"PeriodicalIF":15.7,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145016142","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

Microbiome unlocks cancer immunotherapeutic potential: State of the art and future 微生物组解锁癌症免疫治疗潜力：现状和未来

IF 15.7 1区医学 Q1 ONCOLOGY

Seminars in cancer biology

Pub Date : 2025-09-04 DOI: 10.1016/j.semcancer.2025.08.001

Han-Yue Luo , Lei-Ming Cao , Kan Zhou , Yao Xiao , Zi-Zhan Li , Bing Liu , Lin-Lin Bu

Immunotherapy has overturned the traditional perception of cancer treatment and brought new vitality to the field of oncology, but it still has unresolved problems such as a low response rate and severe side effects. The microbiome has been found to be involved in tumorigenesis, progression, metastasis and immunity modulation. Especially in immunity, the microbiome plays a key role through delicate mechanisms that regulate the immune response not only from the whole body to the local tumor microenvironment but also from innate to adaptive immunity. We summarize the specific relationship between tumor-associated microbiomes at different sites (gut, oral, intratumoral) and cancer immunity, especially pay attention to the microbiome besides the gut. The microbiome-based immunotherapy has been innovatively categorized as follows. ⅰ) Bacteria-based immunotherapy and engineered bacteria as a new strategy to be used in immunotherapy. ⅱ) Microbiome combined with immunotherapy to improve efficacy and mitigate side effects. Finally, we conclude with insights into the shortcomings and future directions of microbiome in immunotherapy.

免疫疗法颠覆了传统的癌症治疗观念，为肿瘤学领域带来了新的活力，但仍存在应答率低、副作用严重等尚未解决的问题。微生物组已被发现参与肿瘤的发生、进展、转移和免疫调节。特别是在免疫方面，微生物组通过微妙的机制发挥关键作用，不仅调节从全身到局部肿瘤微环境的免疫反应，还调节从先天免疫到适应性免疫的免疫反应。我们总结了不同部位（肠道、口腔、肿瘤内）的肿瘤相关微生物组与癌症免疫的具体关系，特别关注了肠道以外的微生物组。基于微生物组的免疫疗法被创新性地分类如下。ⅰ)基于细菌的免疫治疗和工程菌作为免疫治疗的新策略。ⅱ)微生物组联合免疫治疗提高疗效，减轻副作用。最后，我们总结了微生物组在免疫治疗中的不足和未来的发展方向。

{"title":"Microbiome unlocks cancer immunotherapeutic potential: State of the art and future","authors":"Han-Yue Luo , Lei-Ming Cao , Kan Zhou , Yao Xiao , Zi-Zhan Li , Bing Liu , Lin-Lin Bu","doi":"10.1016/j.semcancer.2025.08.001","DOIUrl":"10.1016/j.semcancer.2025.08.001","url":null,"abstract":"<div><div>Immunotherapy has overturned the traditional perception of cancer treatment and brought new vitality to the field of oncology, but it still has unresolved problems such as a low response rate and severe side effects. The microbiome has been found to be involved in tumorigenesis, progression, metastasis and immunity modulation. Especially in immunity, the microbiome plays a key role through delicate mechanisms that regulate the immune response not only from the whole body to the local tumor microenvironment but also from innate to adaptive immunity. We summarize the specific relationship between tumor-associated microbiomes at different sites (gut, oral, intratumoral) and cancer immunity, especially pay attention to the microbiome besides the gut. The microbiome-based immunotherapy has been innovatively categorized as follows. ⅰ) Bacteria-based immunotherapy and engineered bacteria as a new strategy to be used in immunotherapy. ⅱ) Microbiome combined with immunotherapy to improve efficacy and mitigate side effects. Finally, we conclude with insights into the shortcomings and future directions of microbiome in immunotherapy.</div></div>","PeriodicalId":21594,"journal":{"name":"Seminars in cancer biology","volume":"116 ","pages":"Pages 1-21"},"PeriodicalIF":15.7,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005389","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