Current cancer drug targets最新文献

{"title":"Corrigendum to: High Glucose and Glucose-derived Intermediates are Linked to Lung Cancer Aggressiveness.","authors":"Himani Joshi, Raiyan Satti, M Saeed Sheikh","doi":"10.2174/1568009626999260721155854","DOIUrl":"https://doi.org/10.2174/1568009626999260721155854","url":null,"abstract":"<p><p>In the above-mentioned article published in Current Cancer Drug Targets, 2026, 26(4), 393-395, the citation for Fig. (1) was inadvertently omitted. The original article can be found online at: https://www.benthamscience.com/article/150331 Details of the correction are as follows: Original: These findings suggested that the metabolic features associated with metastasis could be utilized as potential therapeutic targets. The authors proposed that, for cancer cells, oxidative metabolism could play an ad-vantageous role in the process of metastasis. However, the exact molecular events underlying increased metastatic burden are unclear and require further investi-gation. Corrected: These findings suggested that the metabolic features associated with metastasis could be utilized as potential therapeutic targets. The authors proposed that, for cancer cells, oxidative metabolism could play an ad-vantageous role in the process of metastasis. However, the exact molecular events underlying increased metastatic burden are unclear and require further investigation (Fig. 1).</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148599995","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":"Reimagining Renal Cell Carcinoma Therapy: Bridging Conventional Gaps with Monoclonal Antibodies (mAbs), Tyrosine Kinase Inhibitors (nibs), and Nanocarriers.","authors":"Sinchani Mandal, Debraj Pal, Inderbir Singh, Tanikan Sangnim, Kampanart Huanbutta","doi":"10.2174/0115680096455669260629111730","DOIUrl":"https://doi.org/10.2174/0115680096455669260629111730","url":null,"abstract":"<p><p>Renal cell carcinoma (RCC), a highly aggressive kidney malignancy, presents significant challenges in early diagnosis, therapeutic resistance, and metastatic progression. Conventional treatment modalities, including surgery, radiotherapy, and chemotherapy, remain essential but are often limited by non-specific toxicity, resistance development, and suboptimal long-term outcomes in advanced stages. In response, molecular-targeted therapies, such as monoclonal antibodies (mAbs) and tyrosine kinase inhibitors, have significantly improved RCC management by selectively disrupting key signaling pathways, including vascular endothelial growth factor (VEGF), plateletderived growth factor (PDGF), and mammalian target of rapamycin (mTOR). However, these therapies still have limitations, including transient responses and systemic adverse effects. Emerging technologies represent promising approaches. Notably, circulating tumor cells (CTCs) are recognized as critical biomarkers in the metastatic cascade, enabling real-time disease monitoring through liquid biopsy. Concurrently, nanotechnology-based platforms, including lipidic and polymeric nanoparticles, have enabled precision drug delivery with enhanced therapeutic efficacy and reduced toxicity. Drug carriers such as liposomes, solid-lipid nanoparticles, and PLGA-based systems successfully deliver chemotherapeutics, siRNAs, and natural compounds targeting key oncogenic pathways, including PI3K-AKT-mTOR (phosphoinositide 3-kinase-protein kinase B (AKT)- mTOR) and VHL-HIF (von Hippel-Lindau tumor suppressor-hypoxia-inducible factor) signaling. Furthermore, multifunctional theranostic platforms integrate diagnostic imaging and therapeutic functions, advancing personalized treatment strategies. Collectively, these innovations represent a paradigm shift from conventional broad-spectrum treatments to intelligent, patient-specific approaches, with the potential to redefine RCC management and improve clinical outcomes.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148548093","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":"Shared Genetic Architecture of Epilepsy and Glioma Revealed by Mendelian Randomization: Identifying Prognostic Biomarkers and Therapeutic Targets.","authors":"Xiangling Feng, Jiahao Zhou, Zhen He, Xiaomin Ying, Tongtong Kan","doi":"10.2174/0115680096474313260623050646","DOIUrl":"https://doi.org/10.2174/0115680096474313260623050646","url":null,"abstract":"<p><strong>Background: </strong>Glioma-Related Epilepsy (GRE) is a hallmark comorbidity of Low-Grade Glioma (LGG), yet the cellular and molecular mechanisms through which germline epilepsy susceptibility converges with tumor biology to shape clinical outcomes remain poorly understood.</p><p><strong>Methods: </strong>Genome-Wide Association Studies (GWAS), expression quantitative trait loci (eQTL) data, single-cell RNA sequencing, and spatial transcriptomics were integrated. Causal inference, phenotype-driven single-cell analyses, and machine learning were applied to identify genetically informed cellular mechanisms underlying GRE.</p><p><strong>Results: </strong>A total of 68 germline loci shared by glioma and epilepsy (FDRIVW < 0.05) were integrated, with microglia and excitatory neurons as the principal mediating cell types. Four seizure-associated genes (WFIKKN1, WDSUB1, SPARCL1, and CALD1) were subsequently identified in TCGA-LGG, with high-confidence enhancer-promoter support for three of them (colco.PP4 > 0.9). A four-gene signature consistently stratified overall survival across three independent cohorts (TCGA-LGG, CGGA_325, and GSE16011) and correlated with immune checkpoint gene expression. High-risk patients showed higher sensitivity to cyclopamine, according to in silico drug response.</p><p><strong>Discussion: </strong>These findings support a neuroimmune model in which pleiotropic germline variants act via microglia and excitatory neurons to link seizure biology with tumor immunity and prognosis. At the same time, in silico therapeutic predictions require functional and multi-ancestry validation.</p><p><strong>Conclusion: </strong>These results reveal a common genetic architecture between glioma and epilepsy, offering candidate biomarkers and therapeutic strategies for the management of GRE.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148454969","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":"Mitochondrial Dynamics as Determinants of Cancer Drug Resistance: A Systematic Review.","authors":"Swaroop Kumar Pandey, Ayush Kulshreshtha, Anuja Mishra","doi":"10.2174/0115680096460139260618104458","DOIUrl":"10.2174/0115680096460139260618104458","url":null,"abstract":"<p><strong>Introduction: </strong>Mitochondria continuously undergo fission and fusion processes, and this dynamic balance is essential for maintaining proper cellular function. Disruption of this balance can lead to cellular dysfunction, making cancer cells more resistant, increasing their metastatic potential, and promoting tumor growth. In this review, we examine how dysregulation of proteins involved in mitochondrial dynamics contributes to drug resistance. We also discuss emerging therapeutic strategies aimed at correcting mitochondrial dysfunction to enhance the effectiveness of cancer therapies.</p><p><strong>Methods: </strong>This review synthesizes recent research on mitochondrial dynamics in cancer. It focuses on key proteins DRP1, MFN1, MFN2, and OPA1 and their roles in mitochondrial fission, fusion, and clearance. The review also integrates current understanding of these processes at the cellular level with emerging findings from studies on drug-resistant cancers.</p><p><strong>Results: </strong>When proteins such as DRP1, MFN1, MFN2, and OPA1 are dysregulated, cancer cells develop mechanisms to survive treatments. These cells alter mitochondrial function, affecting energy production, reactive oxygen species management, and susceptibility to apoptosis. In drug-resistant tumors, mitochondria undergo dynamic remodeling, fusing or dividing depending on cellular requirements. Additionally, mitophagy removes damaged mitochondria while preserving functional ones, further enhancing the survival and resilience of these cells.</p><p><strong>Discussion: </strong>When mitochondria undergo such adaptations, cancer cells can survive hostile environments and evade conventional therapies. Targeting these processes offers therapeutic opportunities: inhibitors of DRP1 can prevent abnormal mitochondrial fission, while modulation of OPA1 or other fusion proteins can restore healthy mitochondrial structure and promote apoptosis. By focusing on mitochondrial dynamics, new strategies emerge to overcome drug resistance by disrupting cancer cell metabolism and organelle homeostasis.</p><p><strong>Conclusion: </strong>This review underscores the potential of mitochondrial dynamics as a promising new target in cancer therapy. Examining the regulation of mitochondrial fission and fusion, the clearance of damaged mitochondria, and the dysregulation of key proteins reveals potential therapeutic opportunities. Furthermore, recent drugs that modulate these processes offer strategies to enhance the durability of cancer treatments and overcome drug resistance.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148430053","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":"Targeted Chemotherapy of Human Breast Cancer Cells Using Docetaxel-Loaded Nanodroplets Coated with Bovine Serum Albumin and Functionalized with Trastuzumab.","authors":"Fatemeh Maghsoudinia, Maryam Atarod, Masoud Mehrgardi, Roghayeh Kamran Samani, Saeid Heidari-Soureshjani","doi":"10.2174/0115680096436900251216080106","DOIUrl":"https://doi.org/10.2174/0115680096436900251216080106","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Breast cancer is the leading cause of cancer-related mortality among women worldwide, highlighting the need for more effective and targeted therapies. This study aimed to investigate the effects of trastuzumab-functionalized docetaxelloaded bovine serum albumin nanodroplets (TRA-DTX-BSA-NDs) on targeted therapy of Human Epidermal Growth Factor Receptor 2 (HER2)-positive breast cancer cells.</p><p><strong>Methods: </strong>TRA-DTX-BSA-NDs were synthesized and characterized for size, morphology, zeta potential, drug entrapment efficiency, and stability. Drug release profiles were assessed under passive conditions and with ultrasound stimulation. In vitro evaluations included biocompatibility testing of SK-BR-3 (cancer) and MCF-10A (normal) cells, cellular uptake analysis, colony formation assays, and apoptosis assays. Ultrasound imaging assessed the echogenic properties of nanodroplets.</p><p><strong>Results: </strong>TRA-DTX-BSA-NDs exhibited a size of 90 ± 5 nm, a zeta potential of +23.4 ± 0.4 mV, and an 84 ± 5% entrapment efficiency. Stability studies showed minimal drug leakage over 90 days. Sustained drug release was observed over 120 hours, with significantly accelerated release upon ultrasound exposure. The nanodroplets showed intense echogenicity. Furthermore, enhanced cellular uptake and selective cytotoxicity toward SK-BR-3 cells were observed. Combination treatment with ultrasound significantly reduced cancer cell viability and colony formation and increased apoptosis.</p><p><strong>Discussion: </strong>TRA-DTX-BSA-NDs represent a dual-function platform for targeted therapy and imaging in HER2-positive breast cancer. The findings align with current research in nanomedicine and highlight the advantages of ultrasound-triggered delivery. Limitations include the need for in vivo studies and long-term safety evaluation.</p><p><strong>Conclusion: </strong>TRA-DTX-BSA-NDs show promise as an in vitro platform for targeted, ultrasound-enhanced chemotherapy, supporting further research into their use for controlled drug-delivery applications.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148396244","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":"Multi-omics Signature Predicts Anti-EGFR Therapy Benefit in Colorectal Cancer Liver Metastases: A Multi-center Cohort Study.","authors":"Yu Liu, Yuan Chen, Guofeng Zhou, Shizhao Zhou, Xueyi Zhang, Songbin Lin, Mengzu Zeng, Liansheng Wang, Jianmin Xu, Wenju Chang","doi":"10.2174/0115680096454400260619162910","DOIUrl":"https://doi.org/10.2174/0115680096454400260619162910","url":null,"abstract":"<p><strong>Introduction: </strong>Clinical management of RAS wild-type colorectal cancer liver metastases (CRLM) remains challenging because many patients exhibit primary resistance to anti-EGFR therapy. Our research centered on the development of a multi-omics deep learning framework, designed to bridge the gap between complex multi-omics data and the necessity for precise therapeutic response forecasting in this specific cohort.</p><p><strong>Materials and methods: </strong>Patient cohorts receiving cetuximab from a prior investigation (PMID: 30305811) constituted the training and testing sets. For external validation, an independent cohort of consecutive patients with RAS wild-type CRLM patients was prospectively enrolled from other institutions between January and December 2018. Utilizing the PyTorch deep learning framework, we initially developed individual radiomic and genetic signatures. Subsequently, computed tomography (CT) images and genetic data were processed through pre-trained ResNet18 and Random Forest models, respectively. The final classification probability of the integrated model was calculated by weighted summation of the output probabilities from the two models, with weights of 3 and 7, respectively.</p><p><strong>Results: </strong>The developed signature demonstrated predictive capability for cetuximab sensitivity, with area under the curve (AUC) values of 0.75 for the radiomic model, 0.81 for the genetic model, and 0.86 for the combined model. In contrast, it did not predict response to chemotherapy (fusion signature AUC: 0.54). Within cohorts treated with cetuximab, the fusion signature proved superior to established biomarkers for identifying treatment-sensitive cases (hazard ratio (HR), 17.9; 95% confidence interval (CI), 3.22-154.31; P = 0.003). Furthermore, it showed a significant correlation with progression-free survival (PFS), with a median PFS of 9.0 versus 5.0 months (HR, 0.44; 95% CI, 0.20-0.99; P = 0.047).</p><p><strong>Discussion: </strong>The proposed multi-omics signature showed a promising ability to identify RAS wild-type CRLM patients more likely to benefit from anti-EGFR therapy using routinely available pretreatment CT and genomic data. Although the external validation cohort was relatively small and further validation is still needed, it may provide a practical tool for early treatment stratification and individualized decision-making.</p><p><strong>Conclusions: </strong>The developed multi-omics signature demonstrated promising performance in predicting sensitivity to anti-EGFR therapy and may help refine survival-based treatment stratification in patients with RAS wild-type CRLM.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359840","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":"Coordinated Roles of T Cells and Natural Killer Cells in Tumor Immunity.","authors":"Ashiq Ali, Wajiha Afzal, Aisha Khatoon, Mohsan Ullah, Kaynaat Akbar, Manahil Zafar, Isra Noor","doi":"10.2174/0115680096454137260622045925","DOIUrl":"https://doi.org/10.2174/0115680096454137260622045925","url":null,"abstract":"<p><p>Both adaptive immune cells, particularly T cells, and innate lymphoid cells, such as Natural Killer (NK) cells, play critical yet complementary roles in tumor immunity. While T cells mediate antigen-specific cytotoxic responses, NK cells provide rapid, innate recognition and elimination of transformed cells, and their interplay can significantly enhance antitumor immunity, offering potential improvements in immunotherapeutic efficacy. Recent studies indicate that NK cells are essential for recruiting type 1 conventional dendritic cells (cDC1) into the tumor microenvironment, which in turn promotes the activation and expansion of tumor-specific CD8+ T cells. Conversely, activated T cells secrete interleukin-2 (IL-2), a cytokine crucial for NK cell proliferation, survival, and cytotoxic function, establishing a positive feedback loop that amplifies immune responses against malignancies. Tumors, however, exploit immune evasion mechanisms, including modulation of the activating receptor NKG2D and its ligands MICA and MICB, to escape detection by both NK and T cells. Furthermore, these lymphocytes share important inhibitory and activating receptor pairs, such as CD161-CLEC2D, TIGIT-CD155, and NKG2A/CD94-HLA-E, which regulate cytotoxic potential and maintain immune homeostasis. Targeting these shared checkpoints or modulating receptor-ligand interactions represents a promising strategy to overcome tumor immune evasion. By elucidating the coordinated actions of NK and T cells and their shared regulatory pathways, novel immunotherapeutic approaches can be developed to enhance antitumor responses, improve treatment efficacy, and ultimately improve clinical outcomes for cancer patients.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148359862","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":"Anticancer Effect and Mechanism of Novel c-Myc Inhibitor BP1 on Hepatocellular Carcinoma.","authors":"Shengkun Cao, Qingqing Yang, Wangwei Xu, Qiaoyun Ni, Qisi Lin","doi":"10.2174/0115680096444603260224040327","DOIUrl":"https://doi.org/10.2174/0115680096444603260224040327","url":null,"abstract":"<p><strong>Introduction: </strong>c-Myc is a pivotal oncogenic transcription factor in hepatocellular carcinoma (HCC), driving tumor progression by regulating genes involved in proliferation, metabolism, and cell survival. Although c-Myc represents an attractive therapeutic target, the development of effective and safe small-molecule inhibitors remains challenging. The present study aimed to evaluate the anticancer activity and underlying mechanism of a newly synthesized c-Myc inhibitor, BP1, in hepatocellular carcinoma.</p><p><strong>Methods: </strong>BP1 was synthesized as a novel small-molecule inhibitor targeting c-Myc. Its antitumor effects were investigated in Huh7 and HepG2 hepatocellular carcinoma cell lines. Cell viability and clonogenic growth were assessed using MTT and colony formation assays, respectively. Cell migration and invasion were examined by wound-healing and Transwell assays. Apoptosis was analyzed by Annexin V/PI flow cytometry. The effects of BP1 on cMyc protein stability, downstream target gene expression, and glycolysis-related enzymes were evaluated by Western blotting and quantitative PCR. In addition, the pharmacokinetic properties of BP1 were characterized in vivo following single-dose administration using LC-MS/MS analysis and compartmental modeling.</p><p><strong>Results: </strong>BP1 treatment markedly reduced cell viability, clonogenic capacity, migration, and invasion in hepatocellular carcinoma cells, while significantly increasing apoptotic cell death. Mechanistic studies showed that BP1 decreased c-Myc protein stability without altering c-Myc mRNA levels, resulting in the suppression of c-Myc-dependent transcriptional programs and downregulation of key glycolytic enzymes. These changes were associated with impaired cellular energy metabolism. Pharmacokinetic analysis revealed rapid systemic clearance and a relatively short plasma half-life of BP1, indicating a low likelihood of drug accumulation following administration.</p><p><strong>Discussion: </strong>The present findings indicate that BP1 exerts its antitumor effects primarily through post-transcriptional destabilization of c-Myc, rather than inhibition of c-Myc gene expression. By disrupting c-Myc-driven metabolic and proliferative signaling pathways, BP1 effectively suppresses multiple malignant phenotypes of hepatocellular carcinoma cells. The observed pharmacokinetic profile further suggests that BP1 may offer advantages in terms of safety related to systemic exposure.</p><p><strong>Conclusion: </strong>BP1 demonstrates potent anticancer activity against hepatocellular carcinoma cells by destabilizing c-Myc, inhibiting proliferation and motility, inducing apoptosis, and interfering with c-Myc-regulated metabolic pathways. In addition to its favorable pharmacokinetic properties, BP1 represents a promising lead compound for further preclinical development in hepatocellular carcinoma.</p>","PeriodicalId":10816,"journal":{"name":"Current cancer drug targets","volume":" ","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148301442","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: GPX4 Inhibition Enhances the Antitumor Effect of PARP Inhibitor on Homologous Recombination Proficient Ovarian Cancer Cells.","authors":"Jiaxin Gu, Senmi Qian, Fangfang Qian, Xiaodong Wu, Lifeng Chen, Xiaojing Chen, Zhuoye Chen, Feifei Song, Mengxia Zheng, Lingfang Wang, Xiaodong Cheng","doi":"10.2174/1568009626999260619160513","DOIUrl":"https://doi.org/10.2174/1568009626999260619160513","url":null,"abstract":"<p><p>In the article titled \"GPX4 Inhibition Enhances the Antitumor Effect of PARP Inhibitor on Homologous Recombination Proficient Ovarian Cancer Cells\", published in Current Cancer Drug Targets, 2026, 26(2), 221-230 [1], Fig no. 2, part (A) was incorrect. The original article can be found online at: https://www.benthamscience.com/issue/14684.</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":"148301056","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":"Spatial Analysis of FAP Gene Expression in Breast Cancer.","authors":"Liubov A Tashireva, Evgeniya S Grigoryeva, Ivan A Patskan, Anna Yu Kalinchuk, Roman V Zelchan","doi":"10.2174/0115680096433584260407101537","DOIUrl":"https://doi.org/10.2174/0115680096433584260407101537","url":null,"abstract":"<p><strong>Introduction: </strong>Fibroblast Activation Protein (FAP) is a key marker of Cancer-Associated Fibroblasts (CAFs) and a promising target for cancer theranostics. However, its expression in both stromal and tumor cells complicates therapeutic strategies.</p><p><strong>Methods: </strong>This study employed spatial transcriptomics to analyze FAP gene expression patterns in luminal breast cancer, revealing distinct molecular profiles in FAP+ stromal cells, FAP+ tumor cells, and tumor cells proximal to FAP+ stroma.</p><p><strong>Results: </strong>FAP+ stromal cells exhibited upregulation of Extracellular Matrix (ECM) remodeling genes (COL1A1, MMP2, TIMP2), secreted factors (CXCL12, POSTN), and immune modulators (CD276), confirming their role in desmoplasia and immunosuppression. In contrast, FAP+ tumor cells showed limited transcriptional changes but elevated POSTN, CD24, and EPCAM, suggesting roles in immune evasion and epithelial plasticity.</p><p><strong>Discussion: </strong>Spatial analysis revealed that tumor cells within 700 μm of FAP+ stroma displayed an aggressive phenotype, marked by ECM degradation (MMP14, COL6A1), mesenchymal markers (VIM), and immune suppression (HLA-DRA, CD276). Conversely, distal tumor cells exhibited metabolic adaptations (ACADSB, SCD) and survival mechanisms (SQSTM1, NUPR1), potentially conferring resistance to therapy.</p><p><strong>Conclusion: </strong>This spatial transcriptomics study elucidates the complex and context-dependent roles of FAP in luminal breast cancer, revealing distinct molecular programs driven by its cellular source and spatial location. We demonstrate that FAP+ CAFs are the primary architects of a profoundly immunosuppressive and pro-fibrotic tumor microenvironment, characterized by extensive ECM remodeling and secretion of CXCL12 and CD276. Furthermore, we identify a novel, aggressive tumor cell subpopulation defined by its proximity to FAP+ stroma, exhibiting a hybrid phenotype with features of ECM degradation, mesenchymal transition, and immune suppression.</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":"148301035","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}