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Synergizing metabolomics and artificial intelligence for advancing precision oncology.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-15 DOI: 10.1016/j.molmed.2025.01.016
Yipeng Xu, Xiaojuan Jiang, Zeping Hu

Metabolomics has emerged as a transformative tool in precision oncology, with substantial potential for advancing biomarker discovery, monitoring treatment responses, and aiding drug development. Integrating artificial intelligence (AI) into metabolomics optimizes data acquisition and analysis, facilitating the interpretation of complex metabolic networks and enabling more effective multiomics integration. In this opinion, we explore recent advances in the application of metabolomics within precision oncology, emphasizing the unique advantages that AI-driven metabolomics offers. We propose that AI not only complements but also amplifies the potential of current platforms, accelerating research progress and ultimately improving patient outcomes. Finally, we discuss the opportunities and challenges involved in translating AI-driven metabolomics into clinical practice for precision oncology.

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引用次数: 0
Molecular subtypes of intrahepatic cholangiocarcinoma.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-14 DOI: 10.1016/j.molmed.2025.01.008
Alessandro De Santis, Lei Zhu, Jianxin Tao, Christoph Reißfelder, Sebastian Schölch

Intrahepatic cholangiocarcinoma (iCCA) presents in two clinically distinct subtypes: large duct (LD-iCCA) and small duct (SD-iCCA). These subtypes exhibit significant molecular, genetic, and histopathological differences that impact patient prognosis and treatment responsiveness. This review advocates for a subtype-specific approach to iCCA research and clinical management, including tailored therapeutic strategies that consider distinct genetic profiles and tumor microenvironments. Current therapeutic approaches hold promise, yet efficacy varies by subtype. Additionally, subtype-specific molecular diagnostics, including DNA methylation-based classifiers and transcriptomic sequencing, have shown potential in refining iCCA subclassification, thereby guiding precision medicine efforts. This article outlines existing clinical trials, key research trajectories, and future directions for developing more effective subtype-adapted therapies for iCCA.

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引用次数: 0
Engineering cytokines for tumor-targeting and selective T cell activation.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-14 DOI: 10.1016/j.molmed.2025.01.010
Kun Peng, Yang-Xin Fu, Yong Liang

Cytokines are promising therapeutic agents for cancer due to their immune-stimulating properties. However, their clinical application is limited by a narrow therapeutic window and dose-limiting on-target, off-tumor toxicity. Advances in protein engineering enable the selective delivery of cytokines to the tumor microenvironment (TME) and antigen-specific T cells, enhancing antitumor efficacy while reducing systemic side effects. This review focuses on selected cytokines and outlines their developmental trajectory for treating solid tumors. We highlight strategies for constructing cis-signaling immunocytokines and procytokines for precise delivery to tumor sites and discuss the biological mechanisms through which these cytokines reactivate antitumor immunity. We also discuss the challenges and future directions for creating more effective cytokine-based therapeutics.

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引用次数: 0
Spatial biology - unravelling complexity within the glioblastoma microenvironment.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-10 DOI: 10.1016/j.molmed.2025.01.014
Stephen D Robinson, Chrysa Filippopoulou, Simoni Besta, Mark Samuels, Andrea L Betrán, Maha Abu Ajamieh, Viviana Vella, William Jones, Georgios Giamas

The advent and refinement of state-of-the-art spatial biology technologies have facilitated analysis that combines the advantages of high-throughput single cell analysis with techniques that preserve tissue architecture. This combination of cellular phenotyping with retained spatial context provides a much greater understanding of cellular interactions within the tumour microenvironment (TME). For glioblastoma, with its significant intra-tumoural heterogeneity, cellular plasticity, and complex TME, appreciating and understanding these spatial patterns may prove key to improving patient outcomes. This review examines the advances in spatial biology techniques, discusses how these methodologies are being applied to study glioblastoma, and explores how spatial information improves understanding of the TME. Ultimately, it is this spatial context that will accelerate the identification of more effective treatments for glioblastoma.

{"title":"Spatial biology - unravelling complexity within the glioblastoma microenvironment.","authors":"Stephen D Robinson, Chrysa Filippopoulou, Simoni Besta, Mark Samuels, Andrea L Betrán, Maha Abu Ajamieh, Viviana Vella, William Jones, Georgios Giamas","doi":"10.1016/j.molmed.2025.01.014","DOIUrl":"https://doi.org/10.1016/j.molmed.2025.01.014","url":null,"abstract":"<p><p>The advent and refinement of state-of-the-art spatial biology technologies have facilitated analysis that combines the advantages of high-throughput single cell analysis with techniques that preserve tissue architecture. This combination of cellular phenotyping with retained spatial context provides a much greater understanding of cellular interactions within the tumour microenvironment (TME). For glioblastoma, with its significant intra-tumoural heterogeneity, cellular plasticity, and complex TME, appreciating and understanding these spatial patterns may prove key to improving patient outcomes. This review examines the advances in spatial biology techniques, discusses how these methodologies are being applied to study glioblastoma, and explores how spatial information improves understanding of the TME. Ultimately, it is this spatial context that will accelerate the identification of more effective treatments for glioblastoma.</p>","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":""},"PeriodicalIF":12.8,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400179","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
The emerging regulatory interface between DNA repair and steroid hormone receptors in cancer.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-10 DOI: 10.1016/j.molmed.2025.01.006
Bim de Klein, Nils Eickhoff, Wilbert Zwart

Human cells potentiate highly diverse functions through tight transcriptional regulation and maintenance of genome integrity. While the DNA damage response (DDR) safeguards the genome, ligand-activated transcription factors, such as steroid hormone receptors (SHRs), provide complex transcriptional outputs. Interestingly, an increasing body of evidence reveals a direct biological and functional interplay between DDR factors and SHR cascades in cancer. SHRs can directly affect DDR gene expression, but DDR factors in turn act as transcriptional coregulators, enabling oncogenic SHR-mediated signaling, which has the potential for novel therapeutic interventions. With a focus on breast and prostate cancer, we describe in this review recent developments in, and insights into, the complex interplay between SHR signaling and the DDR, highlighting opportunities for future clinical interventions.

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引用次数: 0
Thirty years of molecular medicine: reflections from an academic physician-scientist, 1995-2025.
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-05 DOI: 10.1016/j.molmed.2025.01.012
William A Petri
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引用次数: 0
Beyond pluripotency: Yamanaka factors drive brain growth and regeneration. 超越多能性:山中因子驱动大脑生长和再生。
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-12 DOI: 10.1016/j.molmed.2024.11.013
Sunwoo Choi, Mingzi Zhang, Ruslan Rust

The Yamanaka factors (YFs), a set of four transcription factors, are widely studied for their ability to dedifferentiate somatic cells into a pluripotent state. In a recent study, Shen and colleagues show that transient expression of YFs in the mouse brain expands the developing cortex and prevents cognitive decline in an Alzheimer's disease (AD) model.

Yamanaka因子(YFs)是一组四种转录因子,因其能够将体细胞去分化为多能状态而被广泛研究。在最近的一项研究中,Shen和他的同事们发现,YFs在小鼠大脑中的短暂表达扩大了发育中的皮层,并防止了阿尔茨海默病(AD)模型的认知能力下降。
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引用次数: 0
Treating Niemann-Pick C lysosomal storage: approved and emerging approaches. 治疗尼曼-匹克C溶酶体贮积:已批准的和新兴的方法。
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-12-12 DOI: 10.1016/j.molmed.2024.11.011
Andrés D Klein, Emily R Eden, Silvana Zanlungo
{"title":"Treating Niemann-Pick C lysosomal storage: approved and emerging approaches.","authors":"Andrés D Klein, Emily R Eden, Silvana Zanlungo","doi":"10.1016/j.molmed.2024.11.011","DOIUrl":"10.1016/j.molmed.2024.11.011","url":null,"abstract":"","PeriodicalId":23263,"journal":{"name":"Trends in molecular medicine","volume":" ","pages":"195-196"},"PeriodicalIF":12.8,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142822707","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
3-O-acylated bile acids: disrupters or harmonizers of metabolism? 3-O-acylated 胆汁酸:新陈代谢的破坏者还是协调者?
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-06-25 DOI: 10.1016/j.molmed.2024.06.003
Runzhi Chen, Xinhua Chen, Jiangtao Gao

Unveiling a metabolic mystery, this article explores how 3-O-acylated bile acids, specifically 3-O-succinylated cholic acid (3-sucCA) and 3-acetylated cholic acid (3-acetyCA), modified by gut microbes Bacteroides uniformis and Christensenella minuta, respectively, may either disrupt or harmonize our metabolic processes, offering novel therapeutic avenues for conditions such as metabolic dysfunction-associated steatohepatitis (MASH) and type 2 diabetes mellitus (T2D).

本文揭开了新陈代谢的神秘面纱,探讨了 3-O-acylated 胆汁酸,特别是 3-O- succinylated 胆酸(3-sucCA)和 3-acetylated 胆酸(3-acetyCA)如何分别被肠道微生物均匀乳杆菌(Bacteroides uniformis)和小克里斯滕森氏菌(Christensenella minuta)修饰,从而扰乱或协调我们的新陈代谢过程,为代谢功能障碍相关性脂肪性肝炎(MASH)和 2 型糖尿病(T2D)等疾病提供新的治疗途径。
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引用次数: 0
Emerging therapies in hereditary ataxias. 遗传性共济失调的新兴疗法。
IF 12.8 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2025-02-01 Epub Date: 2024-08-16 DOI: 10.1016/j.molmed.2024.07.008
Mallory L S Eisel, Matthew Burns, Tetsuo Ashizawa, Barry Byrne, Manuela Corti, Sub H Subramony

Recent investigations have defined the pathophysiological basis of many hereditary ataxias (HAs), including loss-of-function as well as gain-of-function mechanisms at either the RNA or protein level. Preclinical studies have assessed gene editing, gene and protein replacement, gene enhancement, and gene knockdown strategies. Methodologies include viral vector delivery of genes, oligonucleotide therapies, cell-penetrating peptides, synthetic transcription factors, and technologies to deliver therapies to defined targets. In this review, we focus on Friedreich ataxia (FRDA) and the polyglutamine ataxias in which translational research is active. However, much remains to be done to identify safe and effective molecules, create ideal delivery methods, and perform innovative clinical trials to prove the safety and efficacy of treatments for these rare but devastating diseases.

最近的研究确定了许多遗传性共济失调(HAs)的病理生理学基础,包括 RNA 或蛋白质水平上的功能缺失和功能获得机制。临床前研究评估了基因编辑、基因和蛋白质置换、基因增强和基因敲除策略。研究方法包括病毒载体传递基因、寡核苷酸疗法、细胞穿透肽、合成转录因子以及向确定靶点传递疗法的技术。在本综述中,我们将重点讨论弗里德里希共济失调(FRDA)和多聚谷氨酰胺共济失调,这些疾病的转化研究十分活跃。然而,要确定安全有效的分子、创造理想的给药方法、进行创新性临床试验以证明这些罕见但具有破坏性疾病的治疗方法的安全性和有效性,还有很多工作要做。
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引用次数: 0
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Trends in molecular medicine
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