Medical Oncology最新文献_第9页

Calcitriol, the active form of vitamin D, induces cell death and purinergic signaling modulation in cutaneous melanoma cells. 骨化三醇是维生素D的活性形式，可诱导皮肤黑色素瘤细胞的细胞死亡和嘌呤能信号调节。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-15 DOI: 10.1007/s12032-026-03412-5

Gilnei Bruno da Silva, Rafael Antônio Narzetti, Paula Dallagnol, Bruna Cristina Ozelame, Daiane Manica, Vítor Henrique Mendes Ramos, Aniela Pinto Kempka, Margarete Dulce Bagatini

{"title":"Calcitriol, the active form of vitamin D, induces cell death and purinergic signaling modulation in cutaneous melanoma cells.","authors":"Gilnei Bruno da Silva, Rafael Antônio Narzetti, Paula Dallagnol, Bruna Cristina Ozelame, Daiane Manica, Vítor Henrique Mendes Ramos, Aniela Pinto Kempka, Margarete Dulce Bagatini","doi":"10.1007/s12032-026-03412-5","DOIUrl":"10.1007/s12032-026-03412-5","url":null,"abstract":"Cutaneous melanoma (CM) is the most aggressive form of skin cancer, characterized by high metastatic potential and resistance to conventional therapies. Evidence suggests that modulation of purinergic signaling, interleukin-6 (IL-6), and NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) may represent promising strategies for treating CM. Calcitriol, the active form of vitamin D, has demonstrated antineoplastic potential across different cancer types. In addition, reports have shown that purinergic signaling can be modulated by calcitriol. However, its mechanism of action on the purinergic system in melanoma remains poorly explored. In this study, we investigated the antineoplastic effects of calcitriol on human cutaneous malignant melanoma cell lines, with a focus on the purinergic system. The cells A375 and SK-MEL-28 were treated with calcitriol at 1, 10, and 50 nM for 24 h, and we analyzed cell viability, mitochondrial membrane potential, apoptotic body detection, migration, and ectonucleotidase enzymatic activity. We also analyzed the expression of ectonucleotidases (CD39 and CD73) and IL-6/NLRP3. We found that calcitriol significantly reduced A375 cell viability, altered mitochondrial potential, inhibited cell migration, and induced the formation of apoptotic bodies. These effects were not observed in SK-MEL-28. Moreover, calcitriol modulated the ectonucleotidases activity and downregulated CD39 and CD73 expression. Additionally, the treatments downregulated IL-6 and NLRP3 expression. Thus, our findings demonstrate that calcitriol exerts antineoplastic effects on melanoma cells via mitochondrial dysfunction, apoptosis-related alterations, inhibition of migration, and modulation of purinergic and inflammatory mediators. Therefore, calcitriol is a promising adjuvant for CM therapy.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13578059/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977044","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Overcoming cordycepin limitations with SLNs-based nanoformulation: formulation development and cytotoxicity evaluation against human breast cancer cells. 以slns为基础的纳米配方克服虫草素的局限性：配方开发和对人类乳腺癌细胞的细胞毒性评估。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-15 DOI: 10.1007/s12032-026-03407-2

Saumyadeep Bora, Ravi Amirthalingam, Bhavana Jodha, Sunita Patel, Deep Pooja, Hitesh Kulhari

{"title":"Overcoming cordycepin limitations with SLNs-based nanoformulation: formulation development and cytotoxicity evaluation against human breast cancer cells.","authors":"Saumyadeep Bora, Ravi Amirthalingam, Bhavana Jodha, Sunita Patel, Deep Pooja, Hitesh Kulhari","doi":"10.1007/s12032-026-03407-2","DOIUrl":"10.1007/s12032-026-03407-2","url":null,"abstract":"Problems of low bioavailability, rapid systemic degradation, non-selective targeting, and high toxicity often mar conventional cancer therapies. Cordycepin (COR), a natural adenosine analogue with potent anticancer activity, particularly against breast cancer, is limited by its high rate of inactivation through the enzyme adenosine deaminase, instability at stomach pH, and poor pharmacokinetics, thus reducing its therapeutic potential. To address these limitations, we have designed a solid lipid nanoparticles (SLNs)-based delivery system for the effective entrapment and release of COR to improve its stability, cellular uptake, and cytotoxic efficacy against MCF-7 human breast cancer cells. The synthesized COR-loaded SLNs (CSLN) were found to be monodispersed, spherical nanoparticles with good physical and chemical stability. In vitro release studies exhibited sustained release behaviour in acidic and physiological conditions, mimicking the endo-lysosomal and systemic circulation pH, respectively. The results of cytotoxicity assays indicated that CSLN significantly enhanced the cytotoxic efficacy of COR against MCF-7 cells as contrasted to the free drug. Improved cellular uptake and greater drug accumulation inside cells led to improved apoptotic activity and thus, more clonogenic activity. These findings suggest that SLNs-based nanoencapsulation is a promising approach for enhancing the therapeutic efficacy and safety of COR for breast cancer therapy.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

DHCR24 promotes endometrial carcinoma progression and is associated with cellular senescence regulation. DHCR24促进子宫内膜癌的进展，并与细胞衰老调控有关。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-15 DOI: 10.1007/s12032-026-03406-3

Fei Li, Yuanyuan Wang, Can Wang, Anastasiia Osipova, Hengyu Wang, Jingshu Hu, Yuan Liu, Xiuwei Chen

{"title":"DHCR24 promotes endometrial carcinoma progression and is associated with cellular senescence regulation.","authors":"Fei Li, Yuanyuan Wang, Can Wang, Anastasiia Osipova, Hengyu Wang, Jingshu Hu, Yuan Liu, Xiuwei Chen","doi":"10.1007/s12032-026-03406-3","DOIUrl":"10.1007/s12032-026-03406-3","url":null,"abstract":"Endometrial carcinoma (EC) is a common gynecological malignancy with an increasing incidence, particularly among younger and obese women. Although early-stage EC generally has favorable outcomes, advanced and recurrent disease remains difficult to treat, highlighting the need for reliable biomarkers and biologically relevant therapeutic targets. DHCR24, a terminal enzyme in cholesterol biosynthesis, has been implicated in tumor progression, but its clinical relevance and biological role in EC remain incompletely defined. In this study, we evaluated DHCR24 expression, prognostic significance, and functional relevance in EC using public transcriptomic datasets, independent clinical specimens, in vitro assays, and an in vivo xenograft model. DHCR24 was significantly upregulated in EC and was associated with advanced FIGO stage, high tumor grade, and poor survival. Functional assays showed that DHCR24 promoted EC cell proliferation, migration, invasion, and tumor growth. Bioinformatics analyses indicated that DHCR24-associated genes were enriched in cholesterol metabolism, PI3K-Akt signaling, PPAR signaling, ECM-receptor interaction, cell cycle regulation, and cellular senescence-related pathways. Further experiments showed that DHCR24 knockdown increased p53, p21, and p16 expression and enhanced SA-β-gal staining, whereas DHCR24 overexpression produced the opposite effects. Reciprocal Co-IP assays suggested a potential association between DHCR24 and p53, indicating a possible link between DHCR24 and p53/p21/p16-related cellular senescence-like changes. Exploratory immunoinformatics analyses further suggested that DHCR24 expression may be associated with immune-related features in EC. Overall, these findings support the potential value of DHCR24 as a prognostic biomarker in EC, although further mechanistic and immunological validation is required before its therapeutic potential can be established.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148977224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Dynamic phosphorylation of cGAS by DNA-PKcs and PPP1CC balances DNA repair and innate immunity. DNA- pkcs和PPP1CC对cGAS的动态磷酸化可平衡DNA修复和先天免疫。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03385-5

Jin Jia, Shuting Lai, Shanshan Gao, Hejiang Guo, Saiyu Li, Hua Guan, Zhenyang Yu, Ping-Kun Zhou

{"title":"Dynamic phosphorylation of cGAS by DNA-PKcs and PPP1CC balances DNA repair and innate immunity.","authors":"Jin Jia, Shuting Lai, Shanshan Gao, Hejiang Guo, Saiyu Li, Hua Guan, Zhenyang Yu, Ping-Kun Zhou","doi":"10.1007/s12032-026-03385-5","DOIUrl":"10.1007/s12032-026-03385-5","url":null,"abstract":"Cyclic GMP-AMP synthase (cGAS) is a DNA sensor that localizes to both the cytosol and the nucleus, with dynamic nucleocytoplasmic shuttling. In the cytosol, it drives innate immune signaling upon detecting misplaced self-DNA or foreign DNA. In the nucleus, cGAS is normally tethered to chromatin and catalytically silent, but upon genotoxic stress it is reactivated and engages in DNA damage repair.How cGAS temporally coordinates these dual functions during genotoxic stress remains unresolved. In this study, we identified a context-dependent phosphorylation timer in cells with detectable nuclear cGAS that balances cGAS effects on immune signaling and DNA repair. In G1 phase, cGAS is rapidly phosphorylated by DNA-PKcs after irradiation. This modification suppresses cGAS catalytic activity and delays downstream immune signaling without affecting non-homologous end joining (NHEJ) repair, thereby prioritizing DNA repair over immune activation. Subsequent dephosphorylation by PPP1CC, occurring 8-12 h later, releases cGAS from damage sites and reactivates the cGAS-STING pathway.In S phase, phosphorylated cGAS selectively blocks homologous recombination(HR) while preserving NHEJ. This prevents pathway competition and favors rapid and efficient repair.Later, PPP1CC-mediated dephosphorylation inhibits NHEJ, restores HR competence, and reactivates cGAS catalytic activity. These findings reveal a spatiotemporal mechanism that couples DNA repair progression to immune activation, suggesting that the phosphorylation status of cGAS may inform the therapeutic timing of combined radiotherapy and immunotherapy.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Beyond KRASG12C: emerging therapeutic strategies, patent landscape, and clinical progress in targeting KRAS-mutant cancers. 超越KRASG12C：针对kras突变癌症的新兴治疗策略、专利前景和临床进展。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03392-6

Srijita Chatterjee, Swati Arya, Nidhi Sharma, Madhuri Grover, Divya Yadav, Hiba Parveen

{"title":"Beyond KRASG12C: emerging therapeutic strategies, patent landscape, and clinical progress in targeting KRAS-mutant cancers.","authors":"Srijita Chatterjee, Swati Arya, Nidhi Sharma, Madhuri Grover, Divya Yadav, Hiba Parveen","doi":"10.1007/s12032-026-03392-6","DOIUrl":"10.1007/s12032-026-03392-6","url":null,"abstract":"One of the most commonly mutated oncogenes is Kirsten rat sarcoma viral oncogene homolog (KRAS, which is found in nearly all pancreatic ductal adenocarcinomas (PDAC), is commonly found in colorectal cancers (CRC), and is found in significant numbers in non-small-cell lung cancers (NSCLC). For most of its history, KRAS has been regarded as \"undruggable.\" Still, with recent developments in covalent inhibitors targeting KRAS^G12C, specifically sotorasib and adagrasib, it has now been validated as a viable therapeutic target. Unfortunately, most KRAS mutations occur outside KRAS^G12C and thus require alternative therapeutic strategies beyond those already available. This review summarizes the fast-moving developments in the world of allele-specific and pan-KRAS inhibitors with reference to patent filings, clinical trials, and combinations with other agents. New classes of KRAS inhibitors have recently emerged, including non-covalent inhibitors (MRTX1133, RMC-9805), pan-RAS (ON) antagonists (RMC-6236), and KRAS-directed degraders (ASP3082), as well as planned rational combinations of these new KRAS inhibitors with agents targeting SHP2, SOS1, MEK, and immune checkpoint inhibitors. Other factors, including the development of innovative drug delivery systems, the exploration of resistance mechanisms, and the pursuit of synthetic lethality, could facilitate the complexity of treating KRAS-driven cancers. The regulatory environment and commercialization efforts present opportunities and challenges for precision oncology in KRAS-driven cancers globally. Overall, the rapid evolution of KRAS-targeted therapeutic agents represents a shift from allele-specific inhibition towards a strategy that is mutation/context-dependent, thereby creating further clinical translation opportunities and increased patient benefit.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930260","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

p-Coumaric acid inhibits hepatocellular carcinoma through promoting ROS accumulation. 对香豆酸通过促进ROS积累抑制肝细胞癌。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03367-7

Jiahao Zheng, Quanming Zhang, Leyi Wang, Mengcheng Yuan, Yawen Wang, Xinyue Wei, Hang Lian, Xueting Liu, Yange Liu

{"title":"p-Coumaric acid inhibits hepatocellular carcinoma through promoting ROS accumulation.","authors":"Jiahao Zheng, Quanming Zhang, Leyi Wang, Mengcheng Yuan, Yawen Wang, Xinyue Wei, Hang Lian, Xueting Liu, Yange Liu","doi":"10.1007/s12032-026-03367-7","DOIUrl":"10.1007/s12032-026-03367-7","url":null,"abstract":"Hepatocellular carcinoma (HCC) remains one of the most life-threatening diseases. The regulation of redox homeostasis plays a pivotal role in the progression of HCC. p-Coumaric acid (PCA), a naturally occurring compound, exhibits diverse pharmacological activities; however, its potential anti-HCC effects have not been previously reported. This study aimed to investigate the potential anti-HCC effects of PCA, with a focus on its role in modulating reactive oxygen species (ROS) accumulation in HCC cells. The anti-HCC effects of PCA were evaluated through in vitro and in vivo experiments. In vitro assays, including cell growth, proliferation, wound healing, and Transwell migration, assessed PCA's inhibitory effects, while flow cytometry analyzed apoptosis. Mitochondrial function and ROS levels were measured, with the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway's role explored. In vivo, a subcutaneous xenograft mouse model, using NAC as a ROS scavenger, validated PCA's effects. PCA significantly inhibited the growth and proliferation ability of HCC cells. It also impeded cell migration and induced cell shrinkage and apoptosis. Moreover, PCA suppressed the levels of anti-apoptotic and pro-proliferative proteins. From a mechanistic perspective, PCA reduced mitochondrial membrane potential and ATP production, subsequently promoting ROS accumulation. The inhibition of the Nrf2 signaling pathway by PCA further enhanced ROS levels. Hemin, an agonist of the antioxidant enzyme HO-1, counteracts the inhibitory effect of PCA on the viability of HCC cells. And, in vivo experiments demonstrated that the anti-HCC effects of PCA were reversed by N-acetylcysteine, confirming the critical role of ROS in PCA-mediated inhibition of HCC progression. Our findings indicate that PCA suppresses HCC progression by promoting ROS accumulation, suggesting its therapeutic potential for HCC.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization. OLR1通过NF-κB活化和免疫抑制巨噬细胞极化驱动胃癌进展。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03394-4

Zhimin Chen, Yuke Wang, Xiaojia Xu, Min Zhao, Xiao Zhou

{"title":"OLR1 drives gastric cancer progression through NF-κB activation and immunosuppressive macrophage polarization.","authors":"Zhimin Chen, Yuke Wang, Xiaojia Xu, Min Zhao, Xiao Zhou","doi":"10.1007/s12032-026-03394-4","DOIUrl":"10.1007/s12032-026-03394-4","url":null,"abstract":"Gastric cancer remains a leading cause of cancer-related mortality worldwide, and the identification of clinically relevant biomarkers is critical for improving patient outcomes. Oxidized low-density lipoprotein receptor 1 (OLR1) has been implicated in tumor progression; however, its role in gastric cancer and the tumor microenvironment remains unclear. OLR1 expression and clinical significance were analyzed using The Cancer Genome Atlas (TCGA) dataset and validated in gastric cancer cell lines. Gain- and loss-of-function experiments, together with in vitro and in vivo assays, were performed to investigate the biological functions and underlying mechanisms of OLR1 in gastric cancer progression. OLR1 was significantly upregulated in gastric cancer and associated with unfavorable prognosis. Functional analyses demonstrated that OLR1 promoted gastric cancer cell proliferation, migration, and tumor growth. Mechanistically, OLR1 activated NF-κB signaling and facilitated macrophage polarization toward the M2 phenotype, thereby contributing to a protumorigenic microenvironment. OLR1 promotes gastric cancer progression through activation of NF-κB signaling and modulation of macrophage polarization. These findings identify OLR1 as a potential prognostic biomarker and therapeutic target for gastric cancer.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

Cyclooxygenase-2 selective inhibitors in cancer prevention and therapy: inflammopharmacological basis and translational prospects. 环氧化酶-2选择性抑制剂在癌症预防和治疗中的应用：炎症药理学基础和翻译前景。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03395-3

Ruijie Zhang, Jiarui Tang, Yanyan Wang, Shaohua Fan

{"title":"Cyclooxygenase-2 selective inhibitors in cancer prevention and therapy: inflammopharmacological basis and translational prospects.","authors":"Ruijie Zhang, Jiarui Tang, Yanyan Wang, Shaohua Fan","doi":"10.1007/s12032-026-03395-3","DOIUrl":"10.1007/s12032-026-03395-3","url":null,"abstract":"Cyclooxygenase-2 (COX-2) selective inhibitors, originally developed as anti-inflammatory and analgesic agents for musculoskeletal disorders, show improved gastrointestinal safety compared with traditional nonsteroidal anti-inflammatory drugs and have attracted increasing interest for their potential roles in cancer prevention and treatment. Experimental and clinical evidence indicates that blocking the COX-2/prostaglandin pathway can inhibit tumor initiation and progression by modulating chronic inflammation, angiogenesis, apoptosis, tumor immunity and metastatic spread, with particularly strong data in colorectal cancer. At the same time, concerns about cardiovascular toxicity and heterogeneous treatment responses highlight the need for careful patient selection and optimized dosing strategies. This review summarizes the pharmacological characteristics of COX-2 selective inhibitors and current preclinical and clinical evidence for their anticancer activity across different tumor types. We focus on the underlying mechanisms linking COX-2 signaling to tumor biology, resistance to chemotherapy and radiotherapy, and the potential benefits of combining COX-2 inhibitors with cytotoxic drugs, targeted agents or immunotherapy. In addition, we discuss emerging strategies such as biomarker-guided precision use and novel drug delivery systems designed to enhance antitumor efficacy while reducing systemic adverse effects, and we outline key questions that must be addressed before COX-2 selective inhibitors can be more widely and safely integrated into oncology practice.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

From pumps to networks: ABC transporters in leukemia resistance and microenvironmental adaptation. 从泵到网络：ABC转运蛋白在白血病抵抗和微环境适应中的作用。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03400-9

Jyotirmayee, Veerandra Kumar, Malkhey Verma

{"title":"From pumps to networks: ABC transporters in leukemia resistance and microenvironmental adaptation.","authors":"Jyotirmayee, Veerandra Kumar, Malkhey Verma","doi":"10.1007/s12032-026-03400-9","DOIUrl":"10.1007/s12032-026-03400-9","url":null,"abstract":"ATP-binding cassette (ABC) transporters have long been recognized as critical mediators of multidrug resistance (MDR) in leukemia; however, emerging evidence reframes them as adaptive regulators within an integrated resistance network rather than static efflux pumps. This review consolidates recent mechanistic, functional, and translational insights into the role of key transporters, ABCB1 (P-gp), ABCC1 (MRP1), and ABCG2 (BCRP), in drug resistance and microenvironmental adaptation. We describe how stress-responsive transcriptional programs (ATF4/JUN), stromal kinase signaling (PKC-NF-κB), and metabolic reprogramming (ABCC1-glutathione axis) dynamically regulate transporter expression and activity. Additionally, hypoxia/HIF-1α stabilization, lipid raft remodeling, and extracellular vesicle-mediated communication reinforce efflux competence and sustain leukemic stem cell persistence within protective bone marrow niches. Collectively, these data highlight a shift from isolated transporter overexpression toward network-driven multidrug resistance, wherein transcriptional, metabolic, and stromal inputs converge to reduce intracellular drug accumulation and promote relapse. The review also evaluates methodological standards for functional transporter assessment, including inhibitor-controlled efflux assays, and outlines therapeutic strategies targeting regulatory networks, such as stress-pathway inhibition, stromal disruption, and metabolic modulation, to attenuate adaptive efflux and enhance chemosensitivity. Understanding ABC transporters as components of a stress-responsive, microenvironment-integrated network provides a conceptual framework for developing transporter-aware, niche-adapted interventions aimed at overcoming leukemia resistance and achieving durable therapeutic remission.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148920284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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

IGF2BP3 enhances paclitaxel resistance in bladder urothelial carcinoma by recognizing m⁶A-modified CENPA mRNA. IGF2BP3通过识别m6a修饰的CENPA mRNA增强膀胱尿路上皮癌紫杉醇耐药。

IF 4.7 4区医学

Medical Oncology Pub Date : 2026-09-10 DOI: 10.1007/s12032-026-03383-7

HanJie Yi, YongQing Han, Xia Wang, Qing Li, Le Xiong, ShanFeng Li

{"title":"IGF2BP3 enhances paclitaxel resistance in bladder urothelial carcinoma by recognizing m6A-modified CENPA mRNA.","authors":"HanJie Yi, YongQing Han, Xia Wang, Qing Li, Le Xiong, ShanFeng Li","doi":"10.1007/s12032-026-03383-7","DOIUrl":"10.1007/s12032-026-03383-7","url":null,"abstract":"Bladder urothelial carcinoma (BUC) is associated with poor prognosis and chemoresistance. The RNA-binding protein IGF2BP3 has been implicated in the progression and drug resistance of various cancers, but its role in UC remains underexplored. This study aimed to investigate the role of IGF2BP3 in regulating CENPA mRNA stability and its contribution to UC malignancy and paclitaxel (PTX) resistance. We analyzed human BUC cell lines (UMUC3, T24) and their paclitaxel-resistant counterpart (T24/R). The interaction between IGF2BP3 and CENPA mRNA was assessed using RNA immunoprecipitation (RIP), MeRIP-qPCR, and dual-luciferase reporter assays. RNA stability was measured with actinomycin D treatment. Cell migration, invasion, and clonogenic assays were performed to evaluate the impact of IGF2BP3 and CENPA modulation on tumor behavior. In vivo tumorigenicity and paclitaxel response were evaluated using xenograft mouse models. IGF2BP3 directly binds to m6A-modified CENPA mRNA and enhances its stability, thereby sustaining its expression in BUC. IGF2BP3 knockdown markedly decreased CENPA mRNA and protein levels and increased paclitaxel sensitivity. CENPA overexpression restored the migratory, invasive, and clonogenic capacities of IGF2BP3-silenced cells under paclitaxel treatment, whereas mutation of the m6A site abolished this rescue effect, indicating m6A dependency. In vivo, IGF2BP3 silencing suppressed tumor growth and enhanced paclitaxel sensitivity in T24/R-derived xenografts, which was partially reversed by CENPA overexpression. IGF2BP3 promotes malignant phenotype and paclitaxel resistance in BUC by stabilizing CENPA mRNA. Targeting the IGF2BP3-CENPA axis may provide a novel therapeutic strategy to overcome chemoresistance in BUC.","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":"43 10","pages":""},"PeriodicalIF":4.7,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"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