Biomolecules & Therapeutics最新文献

Erratum to "Bioinformatic Analysis to Identify Biomarker Candidates of Complex Karyotype Soft Tissue Sarcomas with CDK4-Amplification" [Biomol Ther 34(2), 379-390 (2026)]. “利用cdk4扩增鉴定复杂核型软组织肉瘤生物标志物候选物的生物信息学分析”[生物医学杂志]34(2),379-390（2026）。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.007

Eun-Young Lee, Hyun Sang Cho, June Hyuk Kim, Hyun Guy Kang, Jong Woong Park, Ahyoung Cho, Hye Jin You

引用次数: 0

Erratum to "Molecular Mechanisms Underlying the Anti-Cancer Effects of Tangeretin, a Phytochemical from Citrus Extracts" [Biomol Ther 34(2), 279-290 (2026)]. “柑桔皮苷抗癌作用的分子机制”[j].中国生物医学工程学报，34(2),279-290（2026）。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.002

Seung-Hyeon Ahn, Kyung-Chul Choi

引用次数: 0

Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice. 在N141I突变早老素-2转基因小鼠中，应激通过增加Notch2表达加速抑郁样行为。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.246

Seung Sik Yoo, Sun Mi Gu, Kyung Tak Nam, Jeong Soon Choi, Yong Sun Lee, In Jun Yeo, Ji Eun Yu, Sanghyeon Kim, Dong Won Lee, Hyeon Joo Ham, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong

{"title":"Stress Accelerates Depressive-Like Behaviors through Increase of Notch2 Expression in N141I Mutation Presenilin-2 Transgenic Mice.","authors":"Seung Sik Yoo, Sun Mi Gu, Kyung Tak Nam, Jeong Soon Choi, Yong Sun Lee, In Jun Yeo, Ji Eun Yu, Sanghyeon Kim, Dong Won Lee, Hyeon Joo Ham, Ju Young Chang, Jaesuk Yun, Dong Ju Son, Sang-Bae Han, Jin Tae Hong","doi":"10.4062/biomolther.2025.246","DOIUrl":"10.4062/biomolther.2025.246","url":null,"abstract":"Alzheimer's disease (AD) is characterized by progressive cognitive deterioration and significant depression. However, the mechanisms linking depression to AD pathology remain unclear. Here, we investigated whether Notch2 signaling mediates depression-like behaviors in presenilin-2 (PS2) N141I mutant mice, an early-onset AD model. PS2 wild-type (WT) and mutant (MT) mice aged 12-15 months were subjected to unpredictable chronic mild stress (UCMS) for 4 weeks, followed by sucrose preference, tail-hanging, and forced swimming tests. Behavioral assessments showed that UCMS exacerbated anhedonia and immobility only in PS2 MT mice. Molecular analysis revealed concomitant increases in plasma corticosterone, hippocampal γ-secretase activity, and Notch2 expression, and elevated total and phosphorylated glucocorticoid receptor levels in PS2 MT-UCMS mice. Gene expression profiling of human hippocampal datasets confirmed upregulation of NOTCH2 in Alzheimer's disease and depression. Pharmacological inhibition of γ-secretase and Notch signaling with DAPT normalizes depressive behavior, reduces corticosterone release, attenuates GR phosphorylation, and inhibits Notch2 signaling in PS2 MT mice. These findings identify Notch2 as a pivotal mediator linking chronic stress to molecular changes associated with depression and AD, and suggest that targeting Notch2 signaling may provide therapeutic benefits for comorbid mood and neurodegenerative disorders.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"544-555"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Licochalcone E Ameliorates Hepatic Steatosis in Obese Mice by Activating the Sirt1/AMPK Pathway and Reducing Hepatic Lipid Accumulation. 甘草查尔酮E通过激活Sirt1/AMPK通路和减少肝脏脂质积累改善肥胖小鼠肝脏脂肪变性

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.162

Wen-Chung Huang, Shu-Ju Wu, Xuan-Min Liu, Shu-Chen Cheng, Po-Ting Lin, Chun-Ling Kuo, Chian-Jiun Liou

{"title":"Licochalcone E Ameliorates Hepatic Steatosis in Obese Mice by Activating the Sirt1/AMPK Pathway and Reducing Hepatic Lipid Accumulation.","authors":"Wen-Chung Huang, Shu-Ju Wu, Xuan-Min Liu, Shu-Chen Cheng, Po-Ting Lin, Chun-Ling Kuo, Chian-Jiun Liou","doi":"10.4062/biomolther.2025.162","DOIUrl":"10.4062/biomolther.2025.162","url":null,"abstract":"Licochalcone E is a chalcone isolated from Glycyrrhiza uralensis and G. inflata Batal. This study explored the effect of licochalcone E on improving hepatic steatosis in obese mice and evaluated the role of licochalcone E in regulating lipid accumulation in hepatocytes. In vitro, oleic acid-induced hepatocytes were treated with licochalcone E to investigate its effect on lipid metabolic pathways. In animal experiments, male C57BL/6 mice were fed with a high-fat diet (HFD) and treated with licochalcone E by intraperitoneal injection for 12 weeks to assess its effects on biochemical indexes and hepatic steatosis. Furthermore, mice were fed a methionine/choline-deficient (MCD) diet and administered licochalcone E, followed by evaluation of liver fibrosis. Licochalcone E effectively reduced body weight, epididymal and inguinal fat weight, and adipocyte size in HFD-induced obese mice. Licochalcone E treatment of obese mice also reduced hepatic lipid accumulation and improved hepatocyte steatosis. Licochalcone E regulated the expression of lipogenesis- and lipolysis-related genes in the livers of obese mice and increased AMPK phosphorylation and Sirt1 expression in the liver. Licochalcone E also attenuated hepatic inflammation and oxidative stress in obese mice. Furthermore, treatment of MCD-induced mice with licochalcone E reduced the number of lipid vacuoles and the extent of fibrosis and inhibited liver inflammation. In FL83B hepatocytes, licochalcone E could regulate lipogenesis and lipolysis, and increase the phosphorylation of AMPK and ACC. These findings provide new insights into the role of licochalcone E in regulating lipid metabolism and preventing hepatic steatosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"676-688"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149049/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761155","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferroptosis-Driven Senescence Loop as a Central Amplifier of Osteoarthritis Progression. 嗜铁细胞驱动的衰老环是骨关节炎进展的中心放大器。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.010

Rajib Hossain, Hyun Jae Lee, Md Solayman Hossain, Jiwon Jeong, Choong Jae Lee, Sun-Chul Hwang

{"title":"Ferroptosis-Driven Senescence Loop as a Central Amplifier of Osteoarthritis Progression.","authors":"Rajib Hossain, Hyun Jae Lee, Md Solayman Hossain, Jiwon Jeong, Choong Jae Lee, Sun-Chul Hwang","doi":"10.4062/biomolther.2026.010","DOIUrl":"10.4062/biomolther.2026.010","url":null,"abstract":"Osteoarthritis (OA) is a prevalent, chronic joint disorder characterized by cartilage degradation, synovial inflammation, and extracellular matrix (ECM) remodeling, yet disease-modifying therapies remain elusive. Emerging evidence implicates ferroptosis, an iron-dependent form of regulated cell death driven by lipid peroxidation, and cellular senescence, characterized by growth arrest and a senescence-associated secretory phenotype (SASP), as central contributors to OA pathogenesis. Ferroptotic chondrocytes release reactive lipid species and damage-associated molecular patterns (DAMPs) that induce paracrine senescence in neighboring cells, while senescent cells amplify oxidative stress and ferroptotic susceptibility, forming a self-perpetuating feed-forward loop that accelerates tissue degeneration. Histological, molecular, and in vivo studies demonstrate iron accumulation, lipid peroxidation, glutathione peroxidase 4 (GPX4) depletion, and SASP factor secretion in human OA cartilage, synovium, and animal models, linking these processes to ECM breakdown and joint inflammation. Targeted interventions, alone or in combination, can disrupt this pathological loop, preserve chondrocyte viability, reduce SASP-mediated inflammation, and mitigate cartilage damage. Integration of biomarker-guided patient stratification, advanced imaging, and spatial transcriptomic profiling may enable precision-targeted, disease-modifying therapies. Therefore, elucidating the crosstalk between ferroptosis and senescence offers a conceptual and translational framework for shifting OA management from symptomatic relief toward preservation of joint integrity and long-term disease modification.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"506-518"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149042/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Immunomodulatory Effects of Human Breast Milk-Derived Exosomes on Myeloid Cells and Chondrocytes. 人母乳来源的外泌体对骨髓细胞和软骨细胞的免疫调节作用。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.229

Dahyeon Kwon, Ji Yoon Yoo, Kang-Bin Dan, Ki-Uk Kim, Ji-Yun Lee, Hyeyoung Min

{"title":"Immunomodulatory Effects of Human Breast Milk-Derived Exosomes on Myeloid Cells and Chondrocytes.","authors":"Dahyeon Kwon, Ji Yoon Yoo, Kang-Bin Dan, Ki-Uk Kim, Ji-Yun Lee, Hyeyoung Min","doi":"10.4062/biomolther.2025.229","DOIUrl":"10.4062/biomolther.2025.229","url":null,"abstract":"Human breast milk (HBM) is an ideal nutritional source for the growth and development of infants. In addition, HBM contains hormones, growth factors, microRNAs and exosomes that perform various physiological functions. This study investigates the immunomodulatory effects of HBM-derived exosomes on myeloid cells and chondrocytes, and implications for juvenile idiopathic arthritis. HBM-derived exosomes were isolated and characterized using nanoparticle track analyzer and Western blotting. The HBM-derived exosomes treatment decreased the expression of inflammatory mediators and proinflammatory cytokines in mouse peritoneal macrophages upon lipopolysaccharide stimulation. Flow cytometry analysis of bone marrow-derived macrophages indicated that exosomes promoted M2 polarization, as evidenced by a decrease in cells expressing CD80 (M1 marker) and a concurrent increase in cells expressing M2 marker CD206. In addition, exosome treatment attenuated the mitogen-activated protein kinase signaling pathway by reducing the phosphorylation of extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase, and IκB-α, thereby reducing the expression of inducible nitric oxide synthase, cyclooxygenase-2, metalloprotease (MMP)-1, MMP-3, and MMP-13 in SW1353 chondrocytes following IL-1β stimulation. These findings suggest that HBM-derived exosomes promote macrophage polarization toward an anti-inflammatory M2 phenotype and exert significant immunomodulatory effects.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"689-696"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149045/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adenosine A₁ and A_2A Receptors in Sleep Disorders: Mechanisms and Therapeutic Implications. 睡眠障碍中的腺苷A1和A2A受体：机制和治疗意义。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.070

Hye Jin Jee, Cherin Youn, Haeun Lee, Yi-Sook Jung

{"title":"Adenosine A1 and A2A Receptors in Sleep Disorders: Mechanisms and Therapeutic Implications.","authors":"Hye Jin Jee, Cherin Youn, Haeun Lee, Yi-Sook Jung","doi":"10.4062/biomolther.2026.070","DOIUrl":"10.4062/biomolther.2026.070","url":null,"abstract":"Sleep-wake regulation is controlled by circadian and homeostatic processes, with adenosine acting as a key molecular mediator of homeostatic sleep pressure. Extracellular adenosine accumulates during wakefulness as a result of neuronal energy metabolism, particularly in the basal forebrain, and declines during recovery sleep, thereby reflecting the physiological need for sleep. The sleep-promoting effects of adenosine are mediated primarily by two G protein-coupled receptor subtypes, the adenosine A1 receptor and the adenosine A2A receptor. The adenosine A1 receptor, coupled to inhibitory Gi/o proteins and widely expressed in the cortex, hippocampus, thalamus, and basal forebrain, suppresses wake-promoting neuronal activity and facilitates slow-wave activity during non-rapid eye movement sleep. In contrast, the adenosine A2A receptor, coupled to stimulatory Golf proteins and enriched in the striatum and nucleus accumbens, promotes sleep by activating neurons in the preoptic hypothalamus and engaging the indirect basal ganglia pathway. Despite these well-established roles, the contributions of dysregulation of the adenosine A1 receptor and the adenosine A2A receptor to specific sleep disorders remain incompletely understood. This review examines how signaling of the adenosine A1 receptor and the adenosine A2A receptor is altered in insomnia, obstructive sleep apnea, narcolepsy, and restless legs syndrome, and evaluates the therapeutic potential of receptor-selective strategies for adenosine receptor-targeted treatment.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"461-470"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149043/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Novel Anti-Fibrotic Role of G-Protein-Coupled Receptor 119 in Hepatic Stellate Cells. g蛋白偶联受体119在肝星状细胞中的抗纤维化作用。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.064

Jeongwoo Park, Min Hoo Lee, Hyun Young Kim, Hyo Seon Kim, Sang Kyum Kim, Jin Won Yang, Keon Wook Kang

{"title":"A Novel Anti-Fibrotic Role of G-Protein-Coupled Receptor 119 in Hepatic Stellate Cells.","authors":"Jeongwoo Park, Min Hoo Lee, Hyun Young Kim, Hyo Seon Kim, Sang Kyum Kim, Jin Won Yang, Keon Wook Kang","doi":"10.4062/biomolther.2026.064","DOIUrl":"10.4062/biomolther.2026.064","url":null,"abstract":"Liver fibrosis arises from chronic hepatic injury and remains a major clinical challenge due to the lack of effective therapies. Although G-protein-coupled receptor 119 (GPR119) has been explored as a metabolic target in type 2 diabetes, its role in liver fibrogenesis is not well understood. In this study, the protein and mRNA expression of GPR119 were detected in mouse primary hepatic stellate cells (HSCs) using immunostaining and reverse transcriptase-polymerase chain reaction. The anti-fibrotic activities of GPR119 agonists were assessed in primary HSCs, LX-2 cells, and a carbon tetrachloride (CCl₄)-induced mouse model of liver fibrosis. Treatment with the GPR119 agonists MBX-2982 and GSK1292263 inhibited HSC activation, suppressed transforming growth factor-β1 (TGFβ1)-induced Smad2/3 phosphorylation, and reduced the expression of fibrogenic genes. In vivo, oral administration of MBX-2982 attenuated collagen accumulation and decreased hepatic α-smooth muscle actin and TGFβ expression in CCl₄-treated mice. Mechanistically, MBX-2982 activated AMP-activated protein kinase (AMPK), and pharmacological inhibition of AMPK reversed its anti-fibrogenic effects. MBX-2982 further reduced Smad3 acetylation by disrupting the interaction between Smad3 and p300 and promoting AMPK-dependent proteasomal degradation of p300. These results identify GPR119 as a regulator of HSC activation and highlight GPR119 agonists as promising therapeutic candidates for liver fibrosis.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"666-675"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Caffeic Acid Protects Keratinocytes from PM_2.5 by Regulating ROS, Mitochondrial Integrity, and JNK Activation. 咖啡酸通过调节ROS、线粒体完整性和JNK激活来保护角质形成细胞免受PM2.5的影响。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2025.254

Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Mei Jing Piao, Kyoung Ah Kang, Mahadurage Pasindu Laksara Madhuwantha, Jinny Park, Jin Won Hyun

{"title":"Caffeic Acid Protects Keratinocytes from PM2.5 by Regulating ROS, Mitochondrial Integrity, and JNK Activation.","authors":"Herath Mudiyanselage Maheshika Madhuwanthi Senavirathna, Mei Jing Piao, Kyoung Ah Kang, Mahadurage Pasindu Laksara Madhuwantha, Jinny Park, Jin Won Hyun","doi":"10.4062/biomolther.2025.254","DOIUrl":"10.4062/biomolther.2025.254","url":null,"abstract":"Caffeic acid (CA) is a naturally occurring phenolic compound known for its strong antioxidant and cytoprotective properties. Particulate matter (PM) with an aerodynamic diameter of 2.5 µm (PM2.5) or less is a major atmospheric pollutant that induces excessive oxidative stress and apoptosis in human skin cells, contributing to various adverse effects on the skin. In this study, we investigated the protective role of CA against PM2.5-induced cellular injury in human HaCaT keratinocytes. CA reduced PM2.5-induced reactive oxygen species (ROS) accumulation and mitigated oxidative damage, including lipid peroxidation, protein carbonyl formation, mitochondrial membrane depolarization, and intracellular calcium overload. In addition, CA attenuated PM2.5-induced apoptosis by upregulating B-cell lymphoma 2 (Bcl-2) and suppressing Bcl-2-associated X protein (Bax), caspase-3, caspase-9, and phosphorylated c-Jun N-terminal kinase (phospho-JNK). Collectively, these findings demonstrate that CA protects HaCaT keratinocytes from PM2.5-induced oxidative stress and apoptosis by regulating the Bcl-2/Bax axis and inhibiting JNK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for preventing pollutant-induced skin damage.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"697-708"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Adipocytes as Orchestrators of Multimodal Cancer Therapy Resistance. 脂肪细胞是多模式癌症治疗耐药的协调者。

IF 3.2 3区医学

Biomolecules & Therapeutics Pub Date : 2026-05-01 Epub Date: 2026-04-30 DOI: 10.4062/biomolther.2026.036

Jinseon Park, Jaebeom Cho

{"title":"Adipocytes as Orchestrators of Multimodal Cancer Therapy Resistance.","authors":"Jinseon Park, Jaebeom Cho","doi":"10.4062/biomolther.2026.036","DOIUrl":"10.4062/biomolther.2026.036","url":null,"abstract":"The emergence of therapy resistance remains a formidable barrier to successful clinical outcomes in oncology, necessitating a deeper understanding of the tumor microenvironment (TME) as a dynamic ecosystem. Adipocytes, once viewed as passive energy reservoirs, are now recognized as active orchestrators of tumor progression and multimodal therapy resistance, particularly in adipose-rich malignancies. This review comprehensively delineates the multifaceted mechanisms through which adipocytes shield cancer cells from therapeutic insults, including chemotherapy, targeted agents, and immunotherapies. We analyze the clinical evidence positioning visceral adiposity as a critical determinant of treatment failure and explore the complex molecular interplay driven by the adipocyte-derived secretome, lipid metabolite-mediated metabolic rewiring, and the horizontal transfer of bioactive cargo via adipocyte-derived extracellular vesicles, and adipocyte-mediated remodeling of the TME. Furthermore, we highlight noncanonical roles such as direct organelle donation, lipid-mediated drug sequestration, the enhancement of DNA repair pathways, and the activation of cell adhesion-dependent survival signaling. We also synthesize recent technological advancements employed to interrogate the intricate adipocyte-cancer interaction. Finally, we discuss emerging therapeutic strategies aimed at disrupting the adipocyte-cancer axis, while critically addressing the translational limitations of these interventions in clinical settings, offering a roadmap for integrating metabolic and anti-inflammatory interventions with standard regimens to overcome adipocyte-driven resistance and advance precision oncology.","PeriodicalId":8949,"journal":{"name":"Biomolecules & Therapeutics","volume":"34 3","pages":"491-505"},"PeriodicalIF":3.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13149129/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147761105","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0