Recent patents on anti-cancer drug discovery最新文献

{"title":"CircSERPINE2 Induces Platinum Resistance in Ovarian Cancer via the miR-513a-5p/miR-526b-3p/SEMA7A Axis.","authors":"Zhiyuan Niu, Yuqing Mo, Bikang Yang, Mojian Zhang, Rui Zhong, Shufang Zhang, Sheng Yang, Shuping Peng","doi":"10.2174/0115748928454867260630095521","DOIUrl":"https://doi.org/10.2174/0115748928454867260630095521","url":null,"abstract":"<p><strong>Introduction: </strong>Ovarian cancer (OC) is the third most aggressive gynecological malignancy worldwide, and platinum resistance is a common malignant feature of OC associated with poor clinical prognosis. Circular RNA (circRNA) has been reported in many tumor progressions, including drug resistance. In this study, a new circRNA that mediates OC progression by acting as a ceRNA was identified.</p><p><strong>Methods: </strong>Through high-throughput transcriptome sequencing and bioinformatic analyses, the CircSERPINE2/miR-513a-5p/miR-526b-3p/SEMA7A axis was identified as a potential key factor in the development of platinum resistance in OC. CCK-8, colony formation assay, and flow cytometry confirmed the role of CircSERPINE2 in regulating platinum resistance in OC. Relevant patents were cited by the China National Intellectual Property Administration (CNIPA).</p><p><strong>Results: </strong>In OC cells and subcutaneous xenograft tumors, downregulation of CircSERPINE2 was associated with elevated expression of miR-513a-5p/miR-526b-3p, inactivation of the SEMA7A/ IL-6 pathway, and reduced tumor size following platinum treatment. Furthermore, the CircSERPINE2/SEMA7A axis mediated IL-6 autocrine in OC cells and significantly decreased platinum-induced apoptosis. Moreover, the CircSERPINE2/SEMA7A axis promoted M2 polarization of macrophages in the tumor microenvironment, which in turn impaired platinum sensitivity in ovarian cancer cells.</p><p><strong>Discussion: </strong>Given that circRNAs can act as promising clinical diagnostic biomarkers and therapeutic targets, the development of circRNA vaccine nanocomposites represents a novel and promising therapeutic strategy to potentiate tumor-killing efficacy when combined with chemotherapy regimens. On this basis, our subsequent research will focus on the rational design and development of a tailored nano-drug delivery system for this application.</p><p><strong>Conclusion: </strong>CircSERPINE2 promotes platinum resistance in OC cells and induces an immunosuppressive environment through the miR-513a-5p/miR-526b-3p/SEMA7A axis, highlighting its potential as a target for overcoming platinum resistance in OC.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovations in Diagnosis Immunotherapy and Combination Therapy of Prostate Cancer: A Patent-driven Analysis.","authors":"Ritik Relan, Bhaskar Sambar, Anil Kumar Dudam, Abhishek Kanugo","doi":"10.2174/0115748928464095260706163130","DOIUrl":"https://doi.org/10.2174/0115748928464095260706163130","url":null,"abstract":"<p><strong>Introduction: </strong>Prostate cancer (PC) is the second leading cause of mortality in men. It originates in the prostate glands and may be influenced by genetic factors, ethnicity, diet, age, and other factors.</p><p><strong>Methods: </strong>Consequently, the diagnosis of PC occurs at an advanced stage, which shows high mortality in men. The existing therapies, chemotherapy, surgery, and radiation therapy, have shown limited success. Comparatively, nanotechnology-based approaches are more effective and extend survival rates than conventional ones.</p><p><strong>Results: </strong>The state-of-the-art review explores the novel biomarkers that indicate the disease condition before its progression. The novel biomarkers are the Prostate Health Index (PHI), STHLM3, PCA3, TMPRSS2-ERG Fusion, Prostate-Specific Antigen (PSA), Prostate-Specific Membrane Antigen (PSMA), Tumor Mutational Burden (TMB), Microsatellite Instability (MSI), Androgen Receptor (AR) Mutations, etc. Immunotherapy and targeted therapy have gained tremendous significance in tumor therapy and markedly improved survival rates. The adverse effects observed in conventional therapy are circumvented using immunotherapy and targeted therapy. Recently, novel patent innovations were reported for PC (US 20240319192 A1, US 20240309090 A1, US 20250075278 A1, US 20240181092 A1).</p><p><strong>Discussion: </strong>The novel immunotherapy approaches utilized for PC comprised immune checkpoint inhibitors (PD-1/PD-L1, CTLA-4 inhibitors), Vaccines, and Adoptive Cell Therapy (CAR-T Cells). Similarly, targeted therapy includes Androgen Receptor Signaling Inhibitors, PARP Inhibitors, PI3K/AKT/mTOR Pathway Inhibitors, Tyrosine Kinase Inhibitors (TKIs), and DNA Repair Pathway Targeting Agents, etc. Conclusion: Recent innovations in biomarkers help in the early diagnosis of PC. The advanced stage of PC is well-treated with either single Immunotherapy, targeted therapy, or combinations of both for extending patient survival and hope.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Therapeutic Strategies for Hormone-sensitive Breast Cancer: A Patent Landscape Review.","authors":"Calinca Eliotério Oliveira, José Adão Carvalho Nascimento Júnior, Camila Rangel Santos, Pâmela Danielle Cavalcante Barreto, Izabel Almeida Alves","doi":"10.2174/0115748928444498260516065557","DOIUrl":"https://doi.org/10.2174/0115748928444498260516065557","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Hormone receptor-positive (HR+) breast cancer remains a major therapeutic challenge due to endocrine resistance and disease progression. This study investigates the patent landscape of innovative pharmacological strategies for HR+ breast cancer, highlighting emerging targets, technological trends, and their alignment with clinical development.</p><p><strong>Methods: </strong>Patent documents were identified through searches of the European Patent Office databases via the keywords \"breast cancer and hormone therapy\" in the title and/or abstract, along with the International Patent Classification code A61K. The review also examines clinical trials to evaluate the development and approval of new drugs for medical use.</p><p><strong>Results: </strong>A total of 25 patents were selected. Notably, CDK4/6 inhibitors have emerged as promising agents for controlling tumor progression and overcoming endocrine resistance. Another significant innovation involves the use of PIK3CA inhibitors, which are effective in patients with specific mutations in this gene, which are commonly found in HR+ breast cancers.</p><p><strong>Discussion: </strong>The findings indicate that recent technological developments emphasize targeted mechanisms of action, deeper integration of precision oncology, and a continued shift toward strategies to delay or overcome endocrine resistance. These trends reflect an innovative landscape driving increasingly specific and personalized systemic therapies.</p><p><strong>Conclusion: </strong>This review describes current patent-driven innovations in hormone-sensitive breast cancer, highlighting the focus on precision systemic therapies and combination strategies for advanced disease. However, limited attention to the management of endocrine-related adverse effects reveals a critical unmet need for future research and technological development.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pioneering Paclitaxel Delivery: Next-generation Protein Nanocarriers for Transformative Cancer Therapy.","authors":"Lalit Kumar, Neelam Sharma, Rajeev Arya, Biswajit Dash, Arijit Chaudhuri, Rakesh Kumar, Mridhula Manimaran","doi":"10.2174/0115748928469302260712091914","DOIUrl":"https://doi.org/10.2174/0115748928469302260712091914","url":null,"abstract":"<p><strong>Introduction: </strong>Paclitaxel (PTX) is a widely explored antimitotic drug for the treatment of various cancers; however, various issues like its hydrophilic nature, lack of targeting ability, and toxic side effects may cause a reduction in its therapeutic effectiveness. By enhancing solubility, extending circulation, allowing tumor-targeted distribution, and decreasing systemic side effects, protein-based nanocarriers have arisen as a potential substitute to traditional formulations.</p><p><strong>Methods: </strong>An extensive literature review was carried out in PubMed, ScienceDirect, and Google Scholar databases of articles published in 2015-2025 using search strings that were predefined and included the terms that were related to paclitaxel, protein nanoparticles, and cancer therapy. The studies were used according to pre-established inclusion criteria (original research, proteinbased nanocarriers to deliver PTX, etc.) and exclusion criteria (non-protein carriers, conference abstracts, non-English articles, etc.). Google Patents and Espacenet were used in carrying out patent searches. The most recent articles (n=158) and 11 patents were selected, and relevant data were obtained.</p><p><strong>Results: </strong>Various types of protein nanocarriers greatly increase PTX solubility, encapsulation efficiency, and tumor accumulation through both passive and active targeting mechanisms. Important examples include Abraxane®, pH/redox-responsive gelatin systems, folate-targeted zein nanoparticles demonstrating a more than seven-fold increase in oral bioavailability, and multifunctional ferritin structures including chemo-photodynamic therapy. Clinical and preclinical trials have shown consistently good antitumor activity and reduced toxicity as compared to free paclitaxel.</p><p><strong>Discussion: </strong>Protein nanocarriers provide a flexible way to change the surface and release drugs in response to stimuli. They also solve some of the problems with conventional PTX dosage forms. But there are still problems that need to be solved before we can get scale production, controlled release kinetics, long-term stability, and high drug loading.</p><p><strong>Conclusion: </strong>Next-generation protein-based nanocarriers are a unique way to deliver paclitaxel. They have a greater therapeutic index and lead to better patient outcomes. There is a lot of optimism for precision oncology as these biocompatible technologies continue to be improved and used in clinical settings.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611487","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lomitapide as a Novel Therapeutic Agent in Breast Cancer: Mechanism and Potential Implications.","authors":"Bing-Xuan Wu, Hua-Tao Wu, Yang-Zheng Lan, Xin-Ning Yu, Jing Liu, Wen-Jia Chen","doi":"10.2174/0115748928492261260711230310","DOIUrl":"https://doi.org/10.2174/0115748928492261260711230310","url":null,"abstract":"<p><strong>Introduction: </strong>Breast cancer treatment remains challenged by molecular heterogeneity and drug resistance, highlighting the need for new therapeutic strategies. This study aimed to discover potential anti-breast cancer agents using a drug repurposing strategy.</p><p><strong>Methods: </strong>We screened a library of 192 FDA-approved drugs and identified the lipid-lowering agent lomitapide as a candidate anti-breast cancer compound. Its biological effects were evaluated in MDA-MB-231 and MCF-7 cells, and potential molecular targets were investigated through virtual screening and experimental validation.</p><p><strong>Results: </strong>Lomitapide significantly inhibited cell proliferation, invasion, and migration. Mechanistically, lomitapide directly interacted with ER-α and PPARγ. Moreover, it enhanced the sensitivity of MCF-7 cells to tamoxifen.</p><p><strong>Discussion: </strong>Lomitapide suppresses breast cancer progression through multiple mechanisms and may improve endocrine sensitivity.</p><p><strong>Conclusion: </strong>Lomitapide is a novel repurposed agent for breast cancer treatment. ER-α and PPARγ are potential therapeutic targets.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148611441","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uncovering the Underlying Mechanism of Clotrimazole against Ovarian Cancer by Transcriptomics and Experimental Investigations.","authors":"Xin Wang, Ning Wang, Jiaqian Liao, Guanghao Yang, Yi Zhang, Yinghai Wang, Lei Zhang, Kehui Luo, Linlin Yang, Yue Jia, Hongying Yang","doi":"10.2174/0115748928495928260706053847","DOIUrl":"https://doi.org/10.2174/0115748928495928260706053847","url":null,"abstract":"<p><strong>Introduction: </strong>Ovarian cancer remains the most lethal gynecological malignancy globally. While Clotrimazole (CTZ) exhibits antitumor potential, its specific efficacy and mechanisms in ovarian cancer require elucidation.</p><p><strong>Methods: </strong>Proliferation and apoptosis were assessed in A2780 and SKOV3 cells using CCK-8, colony formation, and Annexin-V/PI assays. Mechanisms were explored via RNA sequencing, molecular docking, qRT-PCR, Western blotting, and immunofluorescence. In vivo efficacy and safety were validated using SKOV3 xenograft models.</p><p><strong>Results: </strong>CTZ inhibited cell viability with 48-h IC50 values of 19.36 µM (A2780) and 46.01 µM (SKOV3). Apoptotic rates increased significantly to 48.4% and 20.3%, respectively. RNA-seq analysis identified 4,066 differentially expressed genes primarily enriched in the HER2/PI3K/AKT pathway. Experimental validation confirmed that CTZ significantly downregulated this pathway in vitro and in vivo. In xenograft tumor models, intraperitoneal CTZ administration reduced tumor volume by 48.68% compared to the vehicle group, with slight systemic toxicity. However, oral administration showed limited efficacy.</p><p><strong>Discussion: </strong>It was found that CTZ inhibits ovarian cancer cell proliferation and induces apoptosis via the HER-2/PI3K/AKT signaling pathway. CTZ may bind to HER-2 and accelerate HER2 protein degradation. The Intraperitoneal administration of CTZ exerts potent in vivo antitumor effects, suggesting that future research should utilize novel drug delivery systems to improve oral bioavailability.</p><p><strong>Conclusion: </strong>CTZ is a promising therapeutic agent and may serve as a novel potent agent for ovarian cancer treatment. Its antitumor effects are at least partially mediated via the inhibition of the HER-2/PI3K/AKT signaling pathway.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148538051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms and Senescence Signatures in Cervical Squamous Cell Carcinoma: Insights from Transcriptomic and Single-cell Analyses.","authors":"Kun Hou, Zhendan Liu, Tao Tang, Fei Yu","doi":"10.2174/0115748928488304260706095439","DOIUrl":"https://doi.org/10.2174/0115748928488304260706095439","url":null,"abstract":"<p><strong>Introduction: </strong>Cervical squamous cell carcinoma remains a major medical challenge worldwide, particularly in low-developed regions. This study integrated bulk transcriptomic (GSE63514) and single-cell RNA sequencing data (GSE168652) to investigate how senescencerelated mechanisms contribute to CESC progression. By leveraging this multi-omics integration, the study provides unprecedented resolution into cell-type-specific senescence programmes and their associated intercellular communication networks that drive CESC pathogenesis.</p><p><strong>Methods: </strong>Differential expression analysis was performed on bulk data, followed by functional enrichment analysis. Single-cell analysis characterised senescence signals across cell types and intercellular communications. Network pharmacology identified potential therapeutic agents targeting senescence pathways.</p><p><strong>Results: </strong>We identified 1,319 upregulated and 913 downregulated genes in tumours compared to normal tissues. Functional enrichment analysis revealed pathways involved in cell cycle arrest (CDKN2A/p16INK4A), DNA repair (DNA2), and extracellular matrix remodelling (MMP12, CTHRC1). CDKN2A mediated growth suppression via p53/Rb signalling, while SASP components (AIM2, CXCL9) and APOC1-associated metabolic dysregulation shaped an immunosuppressive microenvironment. Single-cell analysis showed strong senescence signals in epithelial cells and macrophages, involving CDKN2A and APOC1. MIF and MDK signalling between these cells appeared to support immune evasion and angiogenesis. Network pharmacology indicated possible therapies, including CDK4/6 inhibitors, a strategy supported by findings in related HPV-associated malignancies, as well as MMP12 inhibitors and combinations of PARP inhibitors with immune checkpoint blockade.</p><p><strong>Discussion: </strong>These findings provide a more detailed picture of senescence in CESC, with tumour-suppressive effects through CDKN2A and pro-tumorigenic effects via SASP components and APOC1. Cell-cell interactions involving MIF and MDK may drive immune evasion.</p><p><strong>Conclusion: </strong>This study demonstrated both the promoting and suppressive roles of senescence in CESC and identified potential therapeutic targets, offering hope for improved outcomes in high-risk patients from low-resource regions.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148538008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cuproptosis-related Gene SLC31A1 Correlates with M2 Macrophage Infiltration and Serves as a Potential Therapeutic Target in Glioma: A Comprehensive Analysis of 1573 Samples from TCGA and CGGA Databases.","authors":"Man Hu, Yong Wang, Yang Li, Zhiguo Liu, Guimin Zhang","doi":"10.2174/0115748928461929260701074511","DOIUrl":"https://doi.org/10.2174/0115748928461929260701074511","url":null,"abstract":"<p><strong>Introduction: </strong>Cuproptosis is a newly discovered form of programmed cell death that offers a new perspective on glioma treatment. However, the clinical impacts of CuproptosisRelated Genes (CRGs) in glioma remain largely unclear. This study aimed to investigate the role and biological significance of CRGs in glioma.</p><p><strong>Methods: </strong>The current study included 1573 glioma patients (603 from TCGA and 970 from the CGGA database) with clinicopathological information and mRNA sequencing data. The most relevant gene, SLC31A1, was identified among 16 CRGs through a series of approaches. Functional gene annotation was performed using GO, KEGG, and GSVA. Furthermore, correlations between CRGs and immune cell infiltration were analyzed by ESTIMATE and CIBERSORT algorithms. Single-cell RNA sequencing databases were used to verify the infiltration of M2 macrophages. Lastly, in vitro functional experiments were performed to assess the knockdown effects of SLC31A1 expression on the proliferation and invasion of glioma cells. Transcriptome sequencing of SLC31A1 knockdown cell lines was used to validate the functional enrichment analysis results. Mass spectrometry analysis was used to validate the protein-protein interactions. Immunofluorescence staining was used to co-localize the target protein with PD-L1, and the gene expression level was verified by immunohistochemistry.</p><p><strong>Results: </strong>Among the 16 CRGs, SLC31A1 was highly expressed and had the most important prognostic value. The expression of SLC31A1 increased with the degree of malignancy in glioma. SLC31A1 is an independent prognostic factor for gliomas, and an SLC31A1-based prognostic nomogram can reasonably predict the survival of patients. Functional enrichment analysis revealed that SLC31A1 co-expressed genes are mainly involved in immune and metabolismrelated signaling pathways. CIBERSORT analysis revealed that M2 macrophage cells increased with increasing SLC31A1 expression. SLC31A1 was closely associated with immune checkpoints PD-L1 and TIM3. Knockdown of SLC31A1 in glioma cells decreased cellular proliferation, migration, and invasion in vitro.</p><p><strong>Discussion: </strong>The strong correlation between SLC31A1 and M2 macrophage infiltration, coupled with its interaction with immune checkpoints, suggests that SLC31A1 mediates tumor progression by modulating the immunosuppressive microenvironment. These findings indicate that SLC31A1 is not only a copper transporter but also a key regulator of immune evasion in glioma.</p><p><strong>Conclusion: </strong>This study provides basic evidence that regulating cellular copper levels by targeting SLC31A1 is a feasible and patented therapeutic strategy. The high expression of SLC31A1 could promote the infiltration of M2 macrophages in glioma.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458242","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selenium Supplementation in Children and Adolescents Undergoing Cancer Treatment: An Analysis of the Inflammatory Profile and the Expression of Antioxidant Regulators.","authors":"Pamela Oliveira Delgado, Sarah Isabel Pinto Monteiro do Nascimento Alves, Beatriz da Costa Aguiar Alves, Glaucia Luciano Veiga, Thais Moura Gascón, Fernando Luiz Affonso Fonseca","doi":"10.2174/0115748928375574250502065956","DOIUrl":"https://doi.org/10.2174/0115748928375574250502065956","url":null,"abstract":"<p><strong>Introduction: </strong>Children with tumors experience multiple metabolic alterations, including increased lipid oxidation of free fatty acids, inhibition of lipoprotein lipase, and elevated production of inflammatory cytokines (TNF-α and IL-6), which may contribute to cachexia. The micronutrient selenium, with its antioxidant action, seems to play an important role in controlling metabolic changes.</p><p><strong>Aims: </strong>Thus, we aimed to evaluate the impact of selenium supplementation in children with leukemia and solid tumors through the analysis of inflammatory markers and expression of antioxidant regulatory genes using real-time PCR.</p><p><strong>Methods: </strong>This work recruited patients supplemented with selenium aged 3 to 19 years with leukemias and lymphomas or solid tumors from the Pediatric Oncology Service at FMABC. The inflammatory markers IL-6, TNF-α, RBP4, and Tbars were detected through serum evaluations, and the antioxidant regulatory genes, including Thioredoxin, Glutathione Peroxidase, Nuclear transcription factor kappa β, and Selenoprotein P, were analyzed in whole blood samples by real-time PCR.</p><p><strong>Results: </strong>This study evaluated 26 pediatric oncology patients. No significant differences were observed in Tbars or IL6 concentrations between groups. However, selenium supplementation significantly reduced the expression of SEPP1 (p =0.030), NFKB (p =0.003), and TRX (p =0.007) genes compared to baseline, suggesting a potential modulatory effect of selenium on inflammatory gene expression.</p><p><strong>Conclusion: </strong>This study suggests that selenium supplementation may help modulate inflammatory responses in pediatric oncology patients. While no significant differences were found in Tbars or IL-6, selenium significantly reduced the expression of SEPP1, NFKB, and TRX genes. These results indicate a potential role of selenium in controlling inflammatory gene pathways.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148458220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Phase I Open-label Study of the Safety, Tolerability, and Pharmacokinetics of NHWD-870 HCl in Patients with Lymphoma and Other Advanced Solid Tumors.","authors":"Mingzhu Yin, Xin Li, Zhuomiao Ye, Jinhai Deng, Minghui Zhang, Zhongsha Li, Liang Dong, Shiyao Pei, Anjie Min, Heng Zhang, Liang Zeng, Nong Yang, Yongchang Zhang, Nenghui Wang, Wenjuan Jiang, Juan Su, Qin Zhou, Xiang Chen","doi":"10.2174/0115748928447241260617103928","DOIUrl":"https://doi.org/10.2174/0115748928447241260617103928","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;NHWD-870 HCl is a next-generation oral BET inhibitor (US Patent 10,428,071 B2). We conducted a Phase I dose‑escalation study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;This multicenter, open-label, phase I study used a Bayesian optimal interval (BOIN) dose-escalation design. NHWD-870 HCl was administered once daily on an intermittent schedule (5 days on/2 days off) at doses ranging from 0.5 to 3.5 mg. The primary endpoints were safety, cycle 1 Dose-Limiting Toxicities (DLTs), the maximum tolerated dose (MTD), and the recommended phase II dose (RP2D). Secondary endpoints included Objective Response Rate (ORR), Disease Control Rate (DCR), and pharmacokinetics (PK).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Thirty-one patients received NHWD-870 HCl. Overall, 93.5% (29/31) experienced at least one adverse event (AE), and 83.9% (26/31) experienced at least one treatment-related AE (TRAE). The most common TRAEs were thrombocytopenia (45.2%; grade ≥3, 25.8%), anemia (41.9%; grade ≥3, 12.9%), and increased blood bilirubin (32.3%; grade ≥3, 3.2%). Treatment-related Serious Adverse Events (SAEs) occurred in 4 patients (12.9%; thrombocytopenia, n=3; wound bleeding, n=1), and no treatment-related deaths were reported. Twenty-four patients were evaluable for DLTs, and all 3 DLTs occurred at the 2.75 mg dose level, corresponding to a cycle 1 DLT rate of 30.0%, which was within the BOIN target interval (0.18- 0.42). However, considering the concentration-dependent thrombocytopenia, the occurrence of grade 4 thrombocytopenia at 2.75 mg (2 events), the higher discontinuation rate, and the lessthan-dose-proportional increase in exposure at 2.75 mg, the RP2D was determined to be 2.0 mg on a 5-days-on/2-days-off schedule. Among the 29 response-evaluable patients, the ORR was 3.45%, and the DCR was 69.0%. Durable stable disease was observed in selected patients, including approximately 21 months in melanoma and more than 26 months in NUT carcinoma. PK analyses showed rapid absorption (median Tmax, approximately 1-2 h) and less-than-doseproportional increases in Cmax and AUC over the 0.5-2.75 mg dose range; the mean terminal half-life was approximately 11-16 h, with mild accumulation.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;NHWD-870 HCl showed manageable, predominantly hematologic toxicity, with thrombocytopenia demonstrating clear dose- and exposure-related trends. Although the cycle 1 DLT rate at 2.75 mg was consistent with the BOIN target interval, the occurrence of grade 4 thrombocytopenia, the higher frequency of treatment interruptions and discontinuations, and the subproportional increase in exposure supported selection of 2.0 mg (5 days on/2 days off) as the RP2D. Although the ORR was low, the durable disease control observed in BET-dependent tumors, including NUT carcinoma and DLBCL, supports further biomarker-driven studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;NHWD-870 HCl demonstrated manageable, mainly hematologic toxicity and preliminary antitumor","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":""},"PeriodicalIF":4.1,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148378827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}