Current cancer drug targets最新文献

{"title":"Anlotinib for Advanced Peritoneal Follicular Dendritic Cell Sarcoma: A Case Report and Literature Revie.","authors":"Haiyun Geng, Fang Dai, Haiqing Hua, Mengran Cao, Xinlei Gong","doi":"10.2174/0115680096409948251215113303","DOIUrl":"https://doi.org/10.2174/0115680096409948251215113303","url":null,"abstract":"<p><strong>Introduction: </strong>Follicular dendritic cell sarcoma (FDCS) is a rare malignant tumor that lacks a standardized treatment plan. This report explores the efficacy and feasibility of the multi-target tyrosine kinase inhibitor (TKI) anlotinib as a first-line treatment through an indepth analysis of a case of advanced peritoneal FDCS.</p><p><strong>Case presentation: </strong>An 83-year-old female patient was enrolled and received oral anlotinib therapy due to advanced disease stage, poor physical condition, and her family's strong refusal of intravenous treatment. The treatment results showed that the patient achieved a significant partial response (PR), with a progression-free survival (PFS) of up to 15 months and an overall survival (OS) of 26 months, which far exceeded the treatment effects reported in the literature. Adverse reactions during anlotinib treatment were mild, and the lesions improved with increased dosages after the disease progressed, suggesting that this tumor may have adaptive rather than absolute resistance.</p><p><strong>Conclusion: </strong>This case provides valuable \"real-world\" evidence for the application of anlotinib in the treatment of advanced FDCS. Its success may stem from the close alignment between the drug's mechanism of action and the tumor's pathophysiology. However, this case also reveals unresolved issues, such as the complexity of FDCS diagnosis and the potential value of immunotherapy. Meanwhile, the clinical practice of targeted therapy further validates and promotes the value of molecular subtyping. Only by advancing the integration of molecular subtyping and targeted therapy can broader prospects be achieved for the precise diagnosis and treatment of FDCS.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834771","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":"Effects of Radiotherapy, Immune Checkpoint Inhibitors, and PIM Kinase Inhibition in Castration-Resistant Prostate Cancer.","authors":"Vignesh Chennupati, Matthew Eximond, Anita Nwiloh, Anne Rajkumar-Calkins, Jian Wang, Austin Noah Kirschner","doi":"10.2174/0115680096447552260409104759","DOIUrl":"https://doi.org/10.2174/0115680096447552260409104759","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Immune checkpoint inhibitors (ICIs) have limited efficacy in prostate cancer. Radiation therapy (RT) combined with ICIs and PI3K inhibition may enhance anti-tumor immune activity.</p><p><strong>Methods: </strong>RT-induced cytosolic double-stranded DNA (dsDNA) was measured in human and mouse prostate cancer cell lines as the surrogate upstream marker consistent with cGAS-STING engagement. In a syngeneic mouse model for castration-resistant prostate cancer (Myc-CaP in FVB mice), triple therapies were studied: (1) anti-CTLA-4, anti-PD-1, and RT, and (2) PIM kinase inhibitor PIM447, anti-PD-1, and RT. Mass cytometry (CyTOF) was used to measure the tumor-immune profile.</p><p><strong>Results: </strong>The peak induction of cytosolic dsDNA was at an RT dose of 13 Gy. In the mouse model, triple therapy with anti-CTLA-4, anti-PD-1, and RT doubled the median survival compared to monotherapy (32 days vs 11 to 22 days, p<0.006). Triple therapy with the PIM kinase inhibitor PIM447, anti-PD-1, and RT nearly tripled the median survival compared to PIM447 monotherapy (82 days vs 29 days, p=0.002). Mass cytometry analysis revealed that the combination of anti-PD-1 and RT reduced myeloid-derived suppressor cells and tissue-associated macrophages and enhanced CD8+ T-cell infiltration.</p><p><strong>Discussion: </strong>Although prostate cancer is an immunocold entity, RT can trigger immune activation, consistent with engagement of the cGAS-STING signaling pathway (cytosolic dsDNA serving as a surrogate upstream marker). In triple therapy, RT can enhance the efficacy of ICI and PI3K-targeted drug therapy, significantly improving overall survival in a mouse model of CRPC.</p><p><strong>Conclusions: </strong>A combination of RT, ICIs, and PIM kinase inhibition may help overcome immune resistance in prostate cancer. This combination therapy approach supports further preclinical validation and careful clinical evaluation and warrants further clinical investigation to optimize treatment strategies for CRPC.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834763","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":"PCK2 Promotes Non-Small Cell Lung Cancer Progression via SLC38A2- Mediated Glutamine Uptake and mTORC1 Activation.","authors":"Libo Ruan, Fan Zhang, Ling Xiao, Minjun Zhao, Kewang Xu, Wenjun Zeng, Haiyan Zhang","doi":"10.2174/0115680096423756251125052704","DOIUrl":"https://doi.org/10.2174/0115680096423756251125052704","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Phosphoenolpyruvate carboxykinase 2 (PCK2) contributes to cancer metabolic adaptation, yet its role in glutamine (Gln) transport and downstream signaling in non-small cell lung cancer (NSCLC) under glucose deprivation is unclear. This study aimed to investigate the PCK2-SLC38A2-mTORC1 axis in NSCLC under metabolic stress.</p><p><strong>Methods: </strong>A549 NSCLC cells were subjected to PCK2 knockdown using shRNA. Glutamine transporter expression was assessed via PRM proteomics and Western blot. Proliferation, migration, apoptosis, mTORC1 activity, and autophagy were analyzed under low-glucose conditions. Rescue assays were performed using Gln supplementation or SLC38A2 overexpression. Expression of PCK2 and SLC38A2 was evaluated in NSCLC tissues using immunohistochemistry.</p><p><strong>Results: </strong>PCK2 knockdown reduced Gln transporter levels, especially SLC38A2, and impaired cell proliferation and migration, while inducing apoptosis under low-glucose conditions. These effects were reversed by Gln supplementation or SLC38A2 overexpression. Mechanistically, PCK2 knockdown suppressed mTORC1 signaling and disrupted autophagy flux, both of which were restored by SLC38A2. Clinically, high expression of PCK2 and SLC38A2 was observed in NSCLC tissues and correlated with poor prognosis. Experimental results from both NSCLC patient-derived samples and tissue models demonstrated that downregulation of PCK2 effectively attenuated the progression of non-small cell lung cancer.</p><p><strong>Discussion: </strong>PCK2 promoted NSCLC cell survival and progression by maintaining Gln uptake through SLC38A2, thereby activating mTORC1 and modulating autophagy. These findings support a metabolic adaptation mechanism critical to tumor aggressiveness.</p><p><strong>Conclusion: </strong>The PCK2-SLC38A2-mTORC1 signaling axis sustains NSCLC cell viability under glucose limitation and represents a potential metabolic vulnerability for therapeutic targeting.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834780","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":"Splicing: A New Dimension in Decoding the Complex Traits for Cervical Cancer.","authors":"Varsha Sai B, Ashwini Prabhu, Ratnacaram Chandrahas Koumar","doi":"10.2174/0115680096409242251125093718","DOIUrl":"https://doi.org/10.2174/0115680096409242251125093718","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical cancer continues to pose a significant global health chal-lenge, with relatively high incidence and mortality rates among gynecological malignancies, particularly in developing countries. Complex etiological factors, including genetic predispo-sition, environmental influences, and biological mechanisms, regulate the progression of cer-vical cancer. Recent advances in understanding RNA splicing have contributed to a more de-tailed elucidation of these complexities, presenting a promising avenue for cervical cancer research. Here, we elucidate how alternative splicing events promote the synthesis of diverse protein isoforms that modulate tumorigenesis, progression, and metastasis.</p><p><strong>Methods: </strong>A PubMed and Google Scholar-based literature search was performed to identify genes involved in splicing mechanisms as biomarkers for cervical cancer. The search covered studies published between 2000 and 2024. The following keywords were used: \"splicing,\" \"splicing factors/genes,\" \"gene regulation,\" \"spliceosomes,\" \"splicing as cancer hallmark,\" and \"splicing mechanisms,\" in combination with \"cervical cancer.\" We included only English-language publications related specifically to splicing in cervical cancer.</p><p><strong>Results: </strong>We consolidated major splicing factors identified across genomic studies, clinical research, and mechanistic evaluations related to cervical cancer, which may serve as signifi-cant prognostic and diagnostic biomarkers.</p><p><strong>Conclusion: </strong>These consolidated findings highlight the potential impact of splicing on clinical decision-making, various therapeutic modalities, and personalized medicine. Furthermore, therapeutic strategies targeting splicing mechanisms could lead to novel interventions that im-prove clinical outcomes in cervical cancer patients.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147834901","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":"The Function of PPARα in Cancer Drug Development: A Promising Target for Cancer Treatment.","authors":"Rasiravathanahalli Kaveriyappan Govindarajan, Ragothaman Prathiviraj, Mohammed Qasim Waheeb, Mohammed A Al-Duais, Abdulrahman Asmari, Chellasamy Panneerselvam, Igor Rzhepakovsky, Sergey Povetkin, Hans-Uwe Dahms","doi":"10.2174/0115680096423510251031065737","DOIUrl":"https://doi.org/10.2174/0115680096423510251031065737","url":null,"abstract":"<p><p>Cancer is one of the leading causes of mortality globally. PPAR modulators may hold great potential for the management of cancer patients. PPAR modulators also activate specific transcriptional pathways, regulate immune responses and inflammation, and influence the proliferation of various cancer cell types. In the last decade, emerging evidence has shown that PPARα, a nuclear hormone receptor, can modulate carcinogenesis via exerting effects on one or several characteristic pathological behaviors of cancer. This review summarizes current knowledge of PPARα function in various aspects of cancer development and the modulators that regulate PPARα. Based on the current knowledge, we have discussed the development of a potential modulator targeting PPARα for cancer treatment.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721987","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":"The Regulation of Ferroptosis by circRNAs in Various Cancers.","authors":"Liushan Wei, Jia Yu, Shijie Wu, Guiqin Li, Yina Gong, Jiao Zeng, Xiaoyong Lei, Xiaoyan Yang","doi":"10.2174/0115680096453459260313072912","DOIUrl":"https://doi.org/10.2174/0115680096453459260313072912","url":null,"abstract":"<p><p>Ferroptosis, an iron-dependent and lipid-peroxidation-driven form of regulated cell death, has emerged as a central hub linking tumour initiation, metastatic spread, and resistance to radiotherapy and chemotherapy. At its core, labile Fe²⁺, which is imported via the transferrin/transferrin receptor axis, fuels Fenton chemistry by generating hydroxyl rad-icals that oxidise polyunsaturated fatty acids in membrane phospholipids. Cellular survival is heavily dependent on the system Xc⁻ antiporter, which imports cystine for glutathione (GSH) synthesis and thereby sustains glutathione peroxidase 4 (GPX4)-mediated detoxifi-cation of lipid peroxides. The collapse of this process precipitates ferroptosis, a form of reg-ulated cell death. Circular RNAs (circRNAs), defined as covalently closed, highly stable transcripts, have recently been identified as post-transcriptional regulators of this lethal cas-cade. By acting as effective 'sponges' for microRNAs, they effectively de-repress critical nodes of iron homeostasis, lipid remodelling, and ROS clearance. Select circRNAs have been observed to physically interact with GPX4 or Beclin-1, thereby either restraining or amplifying ferroptotic signalling. Consequently, circRNAs reprogramme the ferroptosis landscape of cancer cells, influencing proliferation, invasion, and therapy response. In this study, we synthesise and critically evaluate the current evidence for circRNA-mediated con-trol of ferroptosis across human malignancies. We also outline how circRNA silencing, over-expression, or genome editing could be exploited to synchronise iron depletion with conven-tional cytotoxic drugs. This offers a rational avenue to overcome chemo- and radio-re-sistance.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722042","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":"Phytochemicals as Promising Therapeutics in Cancer Prevention and Treatment: Mechanisms and Applications.","authors":"Hrudesh Priyadarsan Sahoo, Ranjan Kumar Sahoo, Sidhartha Parida, Biswa Mohan Sahoo, Monalisa Gochhi, Priyanka Dash, Chandan das, Goutam Ghosh, Goutam Rath, Biswakanth Kar","doi":"10.2174/0115680096451740260311114647","DOIUrl":"https://doi.org/10.2174/0115680096451740260311114647","url":null,"abstract":"<p><p>Cancer remains a major cause of global morbidity and mortality, with rising inci-dence and limited effectiveness of conventional therapies due to systemic toxicity, adverse effects, and multidrug resistance. These limitations underscore the need for safer, targeted, and biologically effective therapeutic alternatives. Phytochemicals, naturally occurring compounds such as flavonoids, alkaloids, terpenoids, and polyphenols, have garnered consider-able attention due to their broad-spectrum anticancer activities and favorable safety profiles. This review assesses the therapeutic potential of phytochemicals in cancer prevention and treatment, focusing on their molecular mechanisms, pharmacological relevance, and translational applications. A comprehensive literature survey of peer-reviewed articles, clinical studies, and database reports (2015-2025) was conducted using PubMed, Scopus, Science Direct, and Web of Science with search terms including \"phytochemicals,\" \"plant-derived compound\", \"cancer\", \"tumor\", \"anticancer activity,\" \"molecular mechanisms,\" \"chemopre-vention,\" \"combination therapy,\" and \"chemotherapy\" with Boolean operators. Phytochem-icals demonstrated significant anticancer effects by inhibiting cell proliferation, inducing apoptosis, suppressing angiogenesis, and modulating key oncogenic pathways, such as PI3K/Akt/mTOR, MAPK/ERK, and NF-κB. Clinically approved phytochemical-based drugs, including paclitaxel and vinblastine, validate their therapeutic relevance, while compounds such as curcumin and resveratrol show encouraging outcomes in ongoing studies. Synergistic interactions with conventional chemotherapeutics further enhance their therapeutic potential. Overall, phytochemicals exert multi-targeted actions regulating oxidative stress, inflammation, and cell survival pathways, offering advantages of reduced toxicity and enhanced efficacy. However, challenges such as poor solubility and low bioavailability limit their clinical translation. Continued efforts toward advanced formulations and robust clinical validation are essential to advance their integration into modern cancer therapeutics.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721970","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":"RUVBL1 Influences Immune Infiltration and Prognosis of Patients with Colon Adenocarcinoma.","authors":"Dabin Wu, Huiling Liu, Xuesong Xu, Hang Liu","doi":"10.2174/0115680096397636251129115450","DOIUrl":"https://doi.org/10.2174/0115680096397636251129115450","url":null,"abstract":"<p><strong>Introduction: </strong>RuvB-like protein 1 (RUVBL1) has been reported to be associated with tumor progression in various cancers. However, its role in colon adenocarcinoma (COAD) remains poorly understood.</p><p><strong>Methods: </strong>RUVBL1 mRNA and protein expression in COAD were analyzed using the Gene Expression Profiling Interactive Analysis 2 (GEPIA2) and UALCAN databases, respectively. The prognostic value of RUVBL1 was assessed based on The Cancer Genome Atlas (TCGA)-COAD datasets. Quantitative real-time PCR (qRT-PCR), immunofluorescence, and western blot assays were performed to confirm RUVBL1 expression levels in COAD and normal colon samples. RUVBL1-related genes in the TCGA-COAD datasets were identified using Spearman's correlation analysis, and RUVBL1-related immunomodulators were identified through the Tumor and Immune System Interaction Database (TISIDB). These genes and immunomodulators were subjected to functional enrichment analysis. Immune infiltration analysis was conducted to explore the association between RUVBL1 expression and tumor-infiltrating immune cells in COAD. The methylation status of RUVBL1 and its prognostic significance were analyzed using the MethSurv database.</p><p><strong>Results: </strong>Analysis of the GEPIA2 and UALCAN databases revealed that RUVBL1 expression was upregulated in COAD. Prognostic analysis indicated that RUVBL1 is a risk factor for poor survival in COAD patients. In vitro and in vivo experiments confirmed that RUVBL1 expression was higher in COAD samples compared to normal colon tissues. Functional enrichment analysis showed that RUVBL1-related genes and immunomodulators were primarily involved in immune and methylation-related processes. Immune infiltration analysis demonstrated that RUVBL1 expression was associated with 17 tumor-infiltrating immune cell types and negatively correlated with immune-related scores in COAD. Methylation analysis using the MethSurv database identified two RUVBL1 CpG sites that significantly influence the prognosis of COAD patients.</p><p><strong>Conclusion: </strong>These findings suggest that increased RUVBL1 expression is associated with poor prognosis and altered immune infiltration in COAD patients. RUVBL1 may serve as a potential therapeutic target for COAD.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721980","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":"EGFR and ALK Targeted Therapy Response in Non-Small Cell Lung Cancer Harboring Rare or Resistant Mutations: A Case Report and Molecular Insights.","authors":"Anju Farsana Abdul Gafoor, Preena S Parvathy, C Gopi Mohan, Keechilat Pavithran","doi":"10.2174/0115680096458810260330094454","DOIUrl":"https://doi.org/10.2174/0115680096458810260330094454","url":null,"abstract":"<p><strong>Introduction: </strong>The Non-Small Cell Lung Cancer (NSCLC) with rare genomic alterations poses a significant clinical challenge due to a lack of established therapeutic guidelines.</p><p><strong>Case presentation: </strong>We report the application of a precision medicine strategy integrating genomic profiling with in silico molecular docking to guide therapy for two patients harboring such rare mutations. Genomic analysis identified a rare EGFR exon 18/20 insertion in one patient and a resistant ALK C1156Y mutation in another. Selection of the appropriate drug was carried out using molecular docking simulations, which predicted high binding affinity of the irreversible EGFR inhibitor afatinib for the unique EGFR insertion and of the ALK inhibitor alectinib for the C1156Y-mutated kinase. We observed that the computationally-informed choices of afatinib and alectinib subsequently led to notable clinical and radiological improvements in the respective patients.</p><p><strong>Conclusion: </strong>The association between the docking predictions and clinical outcomes corroborates the utility of computational modeling for tailoring therapies, although the structural models provide mechanistic insight into drug efficacy against these rare mutations. The present integrated approach emphasizes the value of merging in silico methods into clinical decision-making to overcome the therapeutic uncertainty of uncommon oncogenic driver alterations.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147722057","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":"Cisplatin Kills Ovarian Cancer Cells by Causing Mitochondrial Oxidative Stress and Death Through the TRPV1 Channel Stimulation: The Role of Eicosapentaenoic Acid.","authors":"Mevlüt Bucak, Mustafa Nazıroğlu","doi":"10.2174/0115680096401368251124072507","DOIUrl":"https://doi.org/10.2174/0115680096401368251124072507","url":null,"abstract":"<p><strong>Introduction: </strong>Cisplatin (Cisp) causes excessive Ca2+ and Zn2+ influxes mediated by TRPV1 channel stimulation and produces a high concentration of mitochondrial (mROS) and cytosolic (cROS) free reactive oxygen radicals. In clinical trials, it can be used in combination with other adjuvant medicinal agents to enhance the safety and efficacy of Cisp. Although contradictory findings exist, eicosapentaenoic acid (EPA) as an adjuvant has been shown to suppress the proliferation of ovarian cancer cells. We assessed the effects of EPA and Cisp incubations on oxidant levels, Zn2+, lysosomal injury, and apoptotic markers in the OVCAR-3 ovarian cancer cell line by activating TRPV1.</p><p><strong>Methods: </strong>Five groups were induced in the cells: control, Cisp (25 μM for 24h), EPA (100 μM for 24h), Cisp + EPA, and Cisp + TRPV1 antagonist (100 M capsazepine, CPZ).</p><p><strong>Results: </strong>Compared with control cells, Cisp mediated upregulation of Ca2+ entry and TRPV1 current density via TRPV1 stimulation in the cells. Cisp-mediated TRPV1 activation includes increases in mROS and cROS, mitochondrial dysfunction, and decreases in glutathione, glutathione peroxidase, OVCAR-3 viability, and number. In response to capsaicin, Cisp-mediated TRPV1 stimulation causes mitochondrial Ca2+ and Zn2+ overload, followed by increases in caspase-3/-8/-9, lysosomal injury, and apoptosis; however, these effects were less pronounced in the Cisp + EPA and Cisp + CPZ groups.</p><p><strong>Discussion: </strong>The tumor cell death effect of Cisp was decreased due to the suppression of TRPV1 caused by the CPZ and EPA incubations. Cisp via TRPV1 activation may therefore be an additional therapeutic approach to increase the susceptibility of ovarian tumor cells to mROS-dependent cell death.</p><p><strong>Conclusion: </strong>We observed that Cisp kills OVCAR-3 cells by stimulating TRPV1; even when the channel is blocked, Cisp retains anti-cancer effects. Cisp and TRPV1 stimulators together may provide an alternative method of killing ovarian cancer cells.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147764964","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}