Current cancer drug targets最新文献

{"title":"Homoharringtonine Impedes Migration and Invasion by Inhibiting EphB4/SRI/EMT Signaling and Enhances the Antimetastatic Abilities of Erlotinib in Pancreatic Cancer.","authors":"Ammar Sarwar, Zeren Zhu, Xiaoyu Tang, Wenjun Tang, Yumeng Cheng, Wenjuan Tang, Qi Su, Tianfeng Yang, Yanmin Zhang, Xianpeng Shi, Man Zhu, Zixi Zhang","doi":"10.2174/0115680096423484251129063926","DOIUrl":"https://doi.org/10.2174/0115680096423484251129063926","url":null,"abstract":"<p><strong>Background: </strong>Homoharringtonine (HHT) is a purified alkaloid compound isolated from the plant Cephalotaxus, traditionally used in Chinese medicine for various ailments, including leukemia. However, the specific role and biological mechanisms by which HHT regulates metastasis in pancreatic cancer (PC) remain unclear. PC is notorious for its high metastatic potential, yet our understanding of the molecular mechanisms driving its metastasis is still limited. The primary aim of this study is to explore the antimetastatic potential of HHT in PC and elucidate its mechanism of inhibiting epithelial-mesenchymal transition (EMT) via EphB4 and SRI.</p><p><strong>Materials and methods: </strong>Western blotting, RT-qPCR, immunofluorescence, and transfection of overexpression and shRNA vectors were employed to examine the expression levels of metastatic factors. Antimetastatic activities were evaluated using scratch and transwell assays. In vitro experiments were complemented by in vivo investigations, supported by immunohistochemistry.</p><p><strong>Results: </strong>We identify a distinct molecular mechanism governing migration, invasion, and metastasis in PC through the EphB4/SRI/EMT pathway. Upregulation of EphB4 increased SRI expression, thereby promoting EMT-associated migration and invasion. A direct interaction between EphB4 and SRI facilitated EMT progression and cellular migration. HHT inhibited EphB4, leading to the downregulation of SRI and reversal of EMT-related markers (E-cadherin and N-cadherin). Moreover, HHT enhanced the antimetastatic effects of erlotinib (ERT) in both in vitro and in vivo PC models.</p><p><strong>Discussion: </strong>The EphB4/SRI/EMT axis emerges as a novel regulatory pathway in PC metastasis, with EphB4 directly interacting with SRI to promote EMT and metastatic behavior. This discovery expands our understanding of the molecular networks driving PC progression, highlighting EphB4 and SRI as potential therapeutic targets. HHT, previously recognized for its antileukemic activity, is shown here to target this axis, reverse EMT, and reduce metastasis. Additionally, the synergistic effect of HHT with ERT suggests a promising combinatorial strategy to overcome the limitations of single-agent targeted therapy, particularly in addressing drug resistance in advanced PC.</p><p><strong>Conclusion: </strong>HHT has been identified as an impediment to cell invasion and metastasis in PC via the EphB4/SRI/EMT axis. Additionally, HHT enhances the efficacy of ERT in inhibiting the migration of PC cells.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301037","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}

{"title":"3D Bioprinted Senescent Caco2 Modeling Using a Low-Cost DIY 3D Bioprinter: Challenges and Limitations.","authors":"Sofian Al Shboul, Yazan Al Dweiri, Mai F AlSakhen, Nisreen Himsawi, Helen Al Zain, Sabal Al Hadidi, Raghda Barham, Nidaa A Ababneh, Ashraf I Khasawneh, Moureq R Alotaibi, Lubna H Tahtamouni, Tareq Saleh","doi":"10.2174/0115680096464735260414205505","DOIUrl":"https://doi.org/10.2174/0115680096464735260414205505","url":null,"abstract":"<p><strong>Background: </strong>Therapy-induced senescence (TIS) is a major component of tumor cell response to a variety of anticancer treatments in preclinical models. Most TIS-related literature is derived from 2D-based studies with limited evidence in 3D models. This study aimed to investigate the challenges of developing an in-house (DIY) 3D bioprinted TIS cell model.</p><p><strong>Materials and methods: </strong>A conventional thermoplastic extrusion-based 3D printer (Anet A8 kit) was modified to function as a bioprinter, enabling the fabrication of a Caco2 cell model via extrusion-based bioprinting. The printed 3D models were exposed to doxorubicin (DOX, at 1 and 10 μM), a well-established TIS trigger, and then assessed for senescence-associated β-galactosidase (SA-β-gal) activity and gene expression of several senescence regulators and components of the senescence-associated secretory phenotype (SASP) via real-time PCR.</p><p><strong>Results: </strong>Treated cells exhibited increased SA-β-gal staining and increased expression of CDKN2A and CDKN2B (and modestly TP53). Furthermore, the expression of SASP-related genes, including MMP3, MMP9, CXCL8, and TGF-β1 (but not IL-1A), was increased, albeit non-significantly, suggesting a potential opportunity to detect transcriptional SASP changes in 3D bioprinted tumor cell models.</p><p><strong>Discussion: </strong>This study provides an early attempt to develop a TIS 3D bioprinted tumor cell model, highlighting several challenges, including infrequent nozzle clogging, difficulty of image-based quantification of SA-β-gal staining, and inter-print variation in gene expression profiles.</p><p><strong>Conclusion: </strong>In-house DIY 3D bioprinting for investigating tumor cell senescence is feasible but requires further improvement prior to use in senolytic screening.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301467","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}

{"title":"Corrigendum to: Influence of DNA Copy Number Aberrations in ABC Transporter Family Genes on the Survival of Patients with Primary Operatable Non-Small Cell Lung Cancer.","authors":"Matvey Mikhailovich Tsyganov, Marina Konstantinovna Ibragimova, Evgeny Olegovich Rodionov, Anastavia Alekseevna Frolova, Irina Aleksandrovna Tsydenova, Elizaveta Andreevna Lutzkaya, Sergey Viktorovich Miller","doi":"10.2174/1568009626999260619162126","DOIUrl":"https://doi.org/10.2174/1568009626999260619162126","url":null,"abstract":"<p><p>In the article titled \"Influence of DNA Copy Number Aberrations in ABC Transporter Family Genes on the Survival of Patients with Primary Operatable Non-Small Cell Lung Cancer\", published in Current Cancer Drug Targets, 2026, 26(2), 256-267 [1], Figure 6 was erroneously cited in the text. The original article can be found online at: https://www.benthamscience.com/issue/14684. Details of the correction are as follows: Original: Therefore, in vitro experiments showed changes in ABC-transporter genes expression profile after chemotherapy drugs expo-sure. Increase in the expression levels of genes in chemotherapy drugs resistant clones may indicate their involvement in multidrug resistance development (Fig. 6). Corrected: Therefore, in vitro experiments showed changes in ABC-transporter genes expression profile after chemotherapy drugs expo-sure. Increase in the expression levels of genes in chemotherapy drugs resistant clones may indicate their involvement in multidrug resistance development (Fig. S1).</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301068","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}

{"title":"Targeting the Tumor Extracellular Matrix: A New Frontier in Cancer Therapy.","authors":"Anjana Goel, Istuti Saraswat, Swadha Pandey","doi":"10.2174/0115680096456643260604051613","DOIUrl":"https://doi.org/10.2174/0115680096456643260604051613","url":null,"abstract":"<p><p>The extracellular matrix (ECM) is a dynamic and multifaceted component of the cellular environment, playing a crucial role in regulating cell behavior, tissue architecture, and overall homeostasis. In the context of cancer, the ECM functions far beyond a structural scaffold; it actively contributes to initiation, progression, and metastasis. Aberrant remodelling of the ECM, characterized by altered protein composition, excessive cross-linking, and increased stiffness, disrupts normal cell signaling and promotes malignant transformation through dysregulated mechanotransduction pathways. The extracellular matrix (ECM) within the tumor microenvironment (TME) is dynamically remodeled. Such remodelling helps cancer cells spread, evade the immune system, and become less likely to respond to standard treatment. More evidence suggests that targeting the extracellular matrix or the enzymes that modify it harmfully could be an effective strategy to treat cancer, either on its own or in combination with current cancer treatments. This review examines new approaches to treating cancer that target the extracellular matrix (ECM). These include breaking down tumor-associated ECM with enzymes, inhibiting lysyl oxidase (LOX/LOXL2) activity, normalizing the matrix, creating drug delivery systems that mimic or respond to ECM, and reprogramming cancer-associated fibroblasts (CAFs). This review suggests that combining mechanistic insights with preclinical and clinical evidence can make treatments more effective in aggressive, stroma-rich cancers by selectively targeting tumor-specific ECM abnormalities instead of causing random ECM disruption. This makes drugs work better and restores immune responses that fight cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148276301","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}

{"title":"CDK Inhibition in Lung Cancer Alters Epithelial-Mesenchymal Transition, Autophagy, and Metabolism.","authors":"Azizeh Alsayyid, Rose Ghemrawi, Nour Sammani, Azza Ramadan, Sedra Kremesh, Molham Sakkal, Nosayba Aldamook, Walaa K Mousa, Mostafa Khair","doi":"10.2174/0115680096414298251201033358","DOIUrl":"https://doi.org/10.2174/0115680096414298251201033358","url":null,"abstract":"<p><strong>Introduction: </strong>Lung cancer remains the leading cause of cancer-related mortality worldwide, responsible for over 1.8 million deaths annually. Despite therapeutic advancements, clinical outcomes in advanced lung adenocarcinoma (LUAD) remain poor due to treatment resistance and metastasis. Cyclin-dependent kinases (CDKs) are essential regulators of cell cycle progression and transcription, yet their therapeutic targeting-especially beyond CDK4 and CDK6-has been largely underexplored in lung cancer. This study investigates the oncogenic relevance of CDK1, CDK2, CDK5, CDK7, and CDK9 in LUAD and evaluates the effects of two pharmacological CDK inhibitors: Roscovitine (a broad-spectrum CDK inhibitor) and RO-3306 (a CDK1-selective inhibitor).</p><p><strong>Methods: </strong>Gene expression levels of CDK family members were analyzed using the UALCAN tool, based on the Cancer Genome Atlas (TCGA) LUAD dataset. LUAD cell lines A549 and H292 were treated with Roscovitine and RO-3306 at various concentrations and durations. Cell viability was assessed using the MTT assay; migration was evaluated through wound healing assays. Protein expression of autophagy markers, epithelial-to-mesenchymal transition marker, and metabolic stress markers was assessed by Western blotting.</p><p><strong>Results: </strong>Bioinformatic analysis revealed significant overexpression of CDK1, CDK2, CDK5, CDK7, and CDK9 in LUAD compared to normal lung tissue. Both inhibitors reduced cell viability in a dose- and time-dependent manner, with Roscovitine demonstrating greater potency. Notably, Roscovitine significantly suppressed cell migration and upregulated E-cadherin expression, suggesting reversal of epithelial-to-mesenchymal transition. Additionally, Roscovitine induced complete autophagic flux, as shown by LC3-II accumulation and p62 degradation, along with activation of metabolic stress pathways. In contrast, RO-3306 selectively impaired migration only in H292 cells and triggered incomplete autophagy, indicating a more limited mechanistic effect.</p><p><strong>Discussion: </strong>This study identifies CDK1, CDK2, CDK5, CDK7, and CDK9 as overexpressed and actionable targets in LUAD. Importantly, it reveals for the first time that CDK inhibition- particularly via Roscovitine-modulates both cell migration and autophagy through distinct and potent mechanisms.</p><p><strong>Conclusion: </strong>These findings support the further development of multi-target CDK inhibitors as promising candidates to overcome tumor progression and therapeutic resistance in lung cancer.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270673","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}

{"title":"Therapy-Induced Cellular Senescence in Non-Hodgkin Lymphomas, with Emphasis on Aggressive B-Cell Subtypes: Molecular Mechanisms and Emerging Drug Targets.","authors":"Victor Tomacinschii, Andreea Casian, Maria Robu, Sanda Buruiana, Natalia Sporis, Cristina Dudnic, Adrian Bogdan Tigu, Ciprian Tomuleasa","doi":"10.2174/0115680096479876260608105824","DOIUrl":"https://doi.org/10.2174/0115680096479876260608105824","url":null,"abstract":"<p><strong>Introduction/background: </strong>Therapy-Induced Senescence (TIS) is increasingly recognized as a clinically relevant outcome of anticancer therapy, particularly after sublethal genotoxic stress. In Non-Hodgkin Lymphomas (NHL), TIS may coexist with apoptosis and contribute to treatment heterogeneity by enabling the long-term survival of dam-aged but viable tumor cells. The aim of this article is to synthesize the core molecular mechanisms of TIS in NHL, and to highlight druggable senolytic and senomorphic strate gies that may improve disease control and reduce the risk of relapse.</p><p><strong>Material and methods: </strong>A narrative review was conducted using mechanistic and translational literature addressing DNA Damage Response (DDR) signaling, p53-p21 and p16^INK4a^-RB checkpoint pathways, Senescence-Associated Secretory Phenotype (SASP), epigenetic remodeling, senescence escape, stemness acquisition, and therapeutic targeting of senescent tumor cells. Searches were performed in PubMed / MEDLINE, Scopus, and Google Scholar using combinations of the terms \"therapy-induced senescence\", \"cellular senescence\", \"SASP\", \"senolytic\", \"senomorphic\", and \"senescence escape\". Priority was given to studies published between 2010 and 2026, while older land-mark studies were included when mechanistically essential.</p><p><strong>Results: </strong>TIS is initiated by persistent DDR signaling (ATM/ATR→CHK1/CHK2) with downstream activation of p53-p21 and/or p16^INK4a^-RB pathways, resulting in stable growth arrest. Senescent lymphoma cells may acquire a SASP that remodels the tumor microenvironment and modulates immune responses. Epigenetic reprogramming (e.g., SAHF formation, H3K9me3 dynamics, lamin B1 loss) supports phenotypic plasticity and may enable escape from senescence with stem-like features, contributing to residual dis-ease persistence and relapse biology.</p><p><strong>Discussion: </strong>Therapeutically, senolytic approaches (e.g., BH3 mimetics, BCL-2/BCL-xL antagonists) and senomorphic strategies (targeting SASP regulators such as NF-κB, JAK/STAT, and mTOR) represent potentially actionable therapeutic approaches. Emerging senolytic Chimeric Antigen Receptor T-cell (CAR-T cell) strategies targeting senescence-associated surface programs, such as uPAR, further expand the therapeutic landscape, although these approaches remain at a preclinical stage at the time of writing this review.</p><p><strong>Conclusion: </strong>In lymphomas, TIS is a dynamic stress-adaptation state that can support persistence and relapse. Rational integration of senescence biomarkers, timing-based therapies, and targeted senolytic/senomorphic interventions may enhance long-term treatment efficacy; however, most senescence-targeted strategies remain investigational and require lymphoma-specific clinical validation.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270599","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}

{"title":"Transformative Advances in the Treatment of Melanoma: A Review.","authors":"Rama Tyagi, Vikram Sharma, Kalpesh Yeole, Gayatri Khosla, Raju Wadekar","doi":"10.2174/0115680096412726251202064317","DOIUrl":"https://doi.org/10.2174/0115680096412726251202064317","url":null,"abstract":"<p><p>Recent advancements in melanoma treatment have reinvigorated hope among patients, significantly shifting the therapeutic landscape. A significant advancement in patient outcomes has been realised by applying first-line treatment strategies that include Immune Checkpoint Inhibitors (ICIs) and targeted therapies. Ipilimumab combined with nivolumab has demonstrated superior outcomes, earning a median overall survival surpassing 70 months. This notable success signifies a pivotal shift in the management of advanced melanoma, reflecting effective therapeutic strategies that clinicians can leverage. The advent of new ICIs, such as relatlimab, introduces additional complexities in decision-making for first-line therapy. Understanding the nuances of various treatments will empower physicians to make informed decisions. Several important characteristics, including brain metastases, PD-L1 expression, BRAF mutation status, performance status, and any previous adjuvant treatments, influence the treatment of advanced melanoma. These factors influence the choice of therapy and the potential efficacy in individual cases, underscoring the need for personalised treatment approaches. This review also sheds light on rare melanoma subtypes, particularly uveal melanoma. The FDA approval of tebentafusp and lifileucel has demonstrated potential in extending the survival time of patients with metastatic uveal melanoma. This progress highlights the importance of innovative therapies tailored to unique cancer profiles. By providing recent insights into these evolving treatment options, this review is an invaluable resource for clinicians. It aims to facilitate informed treatment decisions and enhance understanding of the multifaceted challenges in effectively managing advanced melanoma. As new therapies emerge, continuous education and adaptability will be key to optimising patient outcomes.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148270661","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}

{"title":"NRF2-Driven CARM1 Promotes Malignant Progression and Ferroptosis Resistance in Breast Cancer.","authors":"Yin Zhang, Yinan Guan, Hao Yu, Tingting Zhu, Shengjia Wang, Xiaohan Cheng, Jingjing Ma","doi":"10.2174/0115680096452329260608045835","DOIUrl":"https://doi.org/10.2174/0115680096452329260608045835","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;CARM1 has attracted significant attention due to its role in carcinogenesis across a variety of cancers. Ferroptosis has emerged as a prospective target in anticancer therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This study aimed to investigate the role of CARM1 in TNBC progression and ferroptosis regulation, as well as to clarify the underlying molecular mechanism involving NRF2-mediated transcriptional activation of CARM1.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This study combined bioinformatics analysis, in vitro experiments, and in vivo validation to investigate the role of the NRF2-CARM1 axis in TNBC. Public datasets (UCSC Xena, GEPIA2) were analyzed for CARM1/NRF2 expression, correlation, and prognosis. CARM1 and NRF2 were manipulated in BC cells using siRNA/shRNA and overexpression plasmids. Proliferation, migration, and invasion were assessed by CCK-8, colony formation, wound healing, and Transwell assays. Cell apoptosis was assessed via flow cytometry and immunoblotting analysis. Ferroptosis was quantified by lipid peroxidation (TBARS), lipid ROS (BODIPY 581/591 C11), and total iron levels, together with immunoblotting of ferroptosis-related molecules. NRF2 binding to the CARM1 promoter was examined by ChIP and luciferase reporter assays using wild-type (WT) and NRF2-binding-site mutant (MUT) promoter constructs. A xenograft model was used to validate in vivo relevance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;CARM1 and NRF2 were elevated in BC tissues and cells. CARM1 silencing inhibited proliferation, migration, and invasion in BC cells while facilitating cell apoptosis and ferroptosis, as evidenced by increased lipid peroxidation, lipid ROS accumulation, and iron levels. NRF2 positively regulated CARM1 expression and enhanced WT CARM1 promoter activity, whereas mutation of the NRF2-binding site abolished this effect. ChIP further confirmed enrichment of the CARM1 promoter region in NRF2 immunoprecipitates, supporting direct transcriptional activation of CARM1 by NRF2. Functionally, NRF2 overexpression partially rescued the anti-tumor and pro-ferroptotic effects caused by CARM1 depletion. In vivo, CARM1 knockdown inhibited tumor growth and enhanced lipid peroxidation, which was partially reversed by NRF2 overexpression.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;These findings identify a novel NRF2-CARM1 regulatory axis involved in TNBC progression and ferroptosis resistance. NRF2 directly activates CARM1 transcription, thereby promoting malignant behaviors and suppressing ferroptotic cell death in TNBC cells. These results improve the understanding of TNBC biology and suggest that the NRF2- CARM1 pathway may serve as a potential therapeutic target for ferroptosis-based treatment strategies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;NRF2 directly binds to and transcriptionally activates CARM1, thereby enhancing ferroptosis resistance and promoting TNBC progression. These findings reveal a novel molecular mechanism underlying TNBC maligna","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263791","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}

{"title":"Comparing Cisplatin Sensitivity in Conventional 2D Versus Biomaterialfree 3D Spheroid Cultures of Human Cancer and Bone Marrow Stromal Cells.","authors":"Ceri-Anne Suurmond, Zhule Wang, Jose Kooloos, Sterre Andriessen, Sander Leeuwenburgh, Jeroen van den Beucken","doi":"10.2174/0115680096481806260605115025","DOIUrl":"https://doi.org/10.2174/0115680096481806260605115025","url":null,"abstract":"<p><strong>Objective: </strong>Bone metastases represent a devastating complication of primary cancers, significantly impacting patient survival and quality of life. Accelerating the development of novel and effective chemotherapeutic drugs requires reliable in vitro models. Current in vitro models largely rely on conventional 2D set-ups, while 3D spheroid cultures are emerging. However, the correlation between these 2D and 3D configurations regarding chemotherapeutic efficacy remains poorly defined due to discrepancies in cellular assessment methodologies. To achieve a direct, unconfounded comparison of cellular responses to cisplatin treatment, identical analytical assays were deployed across both 2D and 3D culture models.</p><p><strong>Methods: </strong>Cisplatin sensitivity was comparatively evaluated in metastatic human cancer cell lines (PC3 prostate adenocarcinoma and MDA-MB-231 breast adenocarcinoma) cultured in conventional 2D monolayers versus biomaterial-free 3D spheroids. Proliferation and viability assays were used to assess cytotoxicity, with human Bone Marrow Stromal Cells (hBMSCs) as non-malignant controls. Additionally, the effects of acute (24-hour) versus continuous cisplatin exposure regimens on cellular behavior were examined, and drug sensitivity was subsequently correlated with cell doubling time.</p><p><strong>Results: </strong>For all cell types, 3D spheroid cultures exhibited significantly lower sensitivities to cisplatin compared to 2D cultures. This is likely related to both the dimensionality of the 3D spheroids, as evidenced by time- and concentration-dependent cisplatin penetration into hBMSC spheroids, and cell proliferation, as a correlation between cisplatin sensitivity and cell doubling time was observed across the various cell types used. Finally, we showed that continuous exposure to cisplatin affects cell viability in 2D and 3D culture models in a manner comparable to limited exposure during the initial 24 hours of culture, and that cisplatin sensitivity correlates with cell doubling time.</p><p><strong>Discussion: </strong>Methodological similarities in analyzing cell viability were maintained for both 2D and 3D cell culture models when exploring cisplatin. Their dimensionality hampers penetration of cisplatin into the core of 3D spheroids.</p><p><strong>Conclusion: </strong>Overall, our data underscore the dependence of cisplatin sensitivity on the dimensionality of in vitro models (2D vs. 3D.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263786","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}

{"title":"MiR-4295 Attenuates the Sensitivity of Gastric Cancer Cells to Chemotherapy Drugs by Inhibiting BCL2L11.","authors":"Xiaoyan Yang, Liushan Wei, Yuhui Feng, XiaoYong Lei","doi":"10.2174/0115680096424484260406202700","DOIUrl":"https://doi.org/10.2174/0115680096424484260406202700","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;miRNA is a small intranuclear noncoding RNA, approximately 22 nucleotides (nt), that is aberrantly expressed in tumor cells and tissues. They play important regulatory roles in cell proliferation and chemosensitivity. Our study focuses on the expression of miR-4295 and its role in gastric cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Materials and methods: &lt;/strong&gt;Real-time quantitative RT-PCR was used to detect miR-4295 and mRNA expression. Western blots were used to detect protein expression levels. Luciferase reporter test was used to verify BCL2L11 as a potential target for miR-4295. The GEPIA database was used to analyze a prognostic indicator of gastric cancer patients. The CCK-8 kit was used to evaluate the effect of miR-4295 in combination with chemotherapeutic drugs on cell viability.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The results of real-time quantitative reverse transcription polymerase chain reaction showed that the expression level of miR-4295 was significantly upregulated in the cisplatin-resistant gastric cancer cell line SGC-7901/DDP. This study found that the upregulation of miR-4295 expression could significantly inhibit the expression of BCL2L11, while upregulating the expression of Bcl-2, and reducing the sensitivity of gastric cancer cells to chemotherapeutic drugs; while downregulating the expression of miR-4295 would produce the opposite biological effect. Further analysis using the GEPIA database suggested that BCL2L11 might play a potential role in the prognosis assessment of gastric cancer patients, and its expression was significantly correlated with Bcl-2. Additionally, the luciferase reporter gene experiment further verified that BCL2L11 was a potential target gene of miR-4295.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;During the occurrence and development of gastric cancer, the abnormal high expression of miR-4295 is widespread. Studies have shown that the upregulation of miR-4295 expression can significantly enhance the proliferation ability of tumor cells and reduce the sensitivity of cells to chemotherapy drugs such as docetaxel or cisplatin by inhibiting the expression of BCL2L11, while downregulating the expression of miR-4295 can produce the opposite biological effect. The above research results suggest that the regulatory relationship between miR-4295 and BCL2L11 may provide a potential new intervention strategy for the treatment of gastric cancer.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our study suggests that miR-4295 has the potential to be a therapeutic target for gastric cancer by targeting BCL2L11 to function as an oncogenic miRNA in gastric cancer. However, there are still many issues that need to be addressed. More research is required to find the optimal strategy and schedule for down-regulating miR-4295, as well as to determine the most feasible method for delivering this system to tumor cells. In summary, down-regulating miR-4295 is a promising strategy for reversing chemotherapy resistance, but more re","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148257760","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}