Recent patents on anti-cancer drug discovery最新文献

{"title":"Characterization of the Prognosis and Tumor Microenvironment of Cellular Senescence-related Genes through scRNA-seq and Bulk RNA-seq Analysis in GC.","authors":"Guoxiang Guo, Zhifeng Zhou, Shuping Chen, Jiaqing Cheng, Yang Wang, Tianshu Lan, Yunbin Ye","doi":"10.2174/0115748928255417230924191157","DOIUrl":"10.2174/0115748928255417230924191157","url":null,"abstract":"<p><strong>Background: </strong>Cellular senescence (CS) is thought to be the primary cause of cancer development and progression. This study aimed to investigate the prognostic role and molecular subtypes of CS-associated genes in gastric cancer (GC).</p><p><strong>Materials and methods: </strong>The CellAge database was utilized to acquire CS-related genes. Expression data and clinical information of GC patients were obtained from The Cancer Genome Atlas (TCGA) database. Patients were then grouped into distinct subtypes using the \"Consesus- ClusterPlus\" R package based on CS-related genes. An in-depth analysis was conducted to assess the gene expression, molecular function, prognosis, gene mutation, immune infiltration, and drug resistance of each subtype. In addition, a CS-associated risk model was developed based on Cox regression analysis. The nomogram, constructed on the basis of the risk score and clinical factors, was formulated to improve the clinical application of GC patients. Finally, several candidate drugs were screened based on the Cancer Therapeutics Response Portal (CTRP) and PRISM Repurposing dataset.</p><p><strong>Results: </strong>According to the cluster result, patients were categorized into two molecular subtypes (C1 and C2). The two subtypes revealed distinct expression levels, overall survival (OS) and clinical presentations, mutation profiles, tumor microenvironment (TME), and drug resistance. A risk model was developed by selecting eight genes from the differential expression genes (DEGs) between two molecular subtypes. Patients with GC were categorized into two risk groups, with the high-risk group exhibiting a poor prognosis, a higher TME level, and increased expression of immune checkpoints. Function enrichment results suggested that genes were enriched in DNA repaired pathway in the low-risk group. Moreover, the Tumor Immune Dysfunction and Exclusion (TIDE) analysis indicated that immunotherapy is likely to be more beneficial for patients in the low-risk group. Drug analysis results revealed that several drugs, including ML210, ML162, dasatinib, idronoxil, and temsirolimus, may contribute to the treatment of GC patients in the high-risk group. Moreover, the risk model genes presented a distinct expression in single-cell levels in the GSE150290 dataset.</p><p><strong>Conclusion: </strong>The two molecular subtypes, with their own individual OS rate, expression patterns, and immune infiltration, lay the foundation for further exploration into the GC molecular mechanism. The eight gene signatures could effectively predict the GC prognosis and can serve as reliable markers for GC patients.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"530-542"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41159057","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":"CK2B is a Prognostic Biomarker and a Potential Drug Target for Hepatocellular Carcinoma.","authors":"Huiru Dai, Minling Liu, Yuxi Pan, Tingwei Li, Yihang Pan, Zhe-Sheng Chen, Jing Li, Yuchen Liu, Shuo Fang","doi":"10.2174/0115748928262221230925090120","DOIUrl":"10.2174/0115748928262221230925090120","url":null,"abstract":"<p><strong>Background: </strong>Although casein kinase II subunit beta (CK2B) was previously reported to be involved in human cancers, such as hepatocellular carcinoma (HCC), there has been no systematic assessment of CK2B in HCC.</p><p><strong>Objective: </strong>To assess the potential function of CK2B as a prognostic biomarker and possible druggable target in HCC.</p><p><strong>Methods: </strong>The Cancer Genome Atlas database was accessed to investigate the potential oncogenic and prognostic roles of CK2B in HCC. Diverse analytical methods were used to obtain a fuller understanding of CK2B, including CIBERSORT, The Tumor Immune Estimation Resource (TIMER), gene set enrichment analyses (GSEA), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene ontology (GO). Furthermore, the Comparative Toxicogenomic Database (CTD) was used to identify potential drugs to treat _CK2B-overexpressing HCC. Patents for these drugs were reviewed using Patentscope^® and Worldwide Espacenet^®.</p><p><strong>Results: </strong>Upregulated CK2B expression was markedly associated with more aggressive pathological features, including G3, G4 (vs. G1, G2), and T2, T3 (vs. T1). Kaplan-Meier survival curves indicated that patients with HCC with higher expression of CK2B had worse overall survival (P = 0.005), progression-free interval (P = 0.001), and disease-specific survival (P = 0.011). GO and KEGG analysis revealed that CK2B dysregulation affects mitotic chromosome condensation, protein stabilization and binding, regulation of signal transduction of p53 class mediator, and cancer-related pathways. GSEA identified six well-known pathways, including MAPK, WNT, Hedgehog, and TGFβ signaling pathways. Finally, CTD identified six compounds that might represent targeted drugs to treat HCC with _CK2B overexpression. A review of patents indicated these compounds showed promising anticancer results; however, whether CK2B interacts with these drugs and improves drug outcomes for patients with HCC was not confirmed.</p><p><strong>Conclusion: </strong>CK2B is a biomarker for HCC prognosis and could be a potential new drug target. Moreover, the association between infiltrating immune cells and CK2B in the HCC tumor microenvironment might provide a solid basis for further investigation and a potent strategy for immunotherapy of HCC.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"622-634"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41170047","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":"Research Progress on the Anticancer Activity of Plant Polysaccharides.","authors":"Qiaoyan Liu, Bo Song, Sen Tong, Qiuqiong Yang, Huanhuan Zhao, Jia Guo, Xuexia Tian, Renjie Chang, Junzi Wu","doi":"10.2174/1574892819666230915103434","DOIUrl":"10.2174/1574892819666230915103434","url":null,"abstract":"<p><p>Tumor is a serious threat to human health, with extremely high morbidity and mortality rates. However, tumor treatment is challenging, and the development of antitumor drugs has always been a significant research focus. Plant polysaccharides are known to possess various biological activities. They have many pharmacological properties such as immunomodulation, antitumor, antiviral, antioxidative, antithrombotic, and antiradiation effects, reduction of blood pressure and blood sugar levels, and protection from liver injury. Among these effects, the antitumor effect of plant polysaccharides has been widely studied. Plant polysaccharides can inhibit tumor proliferation and growth by inhibiting tumor cell invasion and metastasis, inducing cell apoptosis, affecting the cell cycle, and regulating the tumor microenvironment. They also have the characteristics of safety, high efficiency, and low toxicity, which can alleviate, to a certain extent, the adverse reactions caused by traditional tumor treatment methods such as surgery, radiotherapy, and chemotherapy. Therefore, this paper systematically summarizes the direct antitumor effects of plant polysaccharides, their regulatory effects on the tumor microenvironment, and intervening many common high-incidence tumors in other ways. It also provides data support for the administration of plant polysaccharides in modern tumor drug therapy, enabling the identification of new targets and development of new drugs for tumor therapy.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"573-598"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127424","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":"The Clinical Significance and Prognostic Value of ALDH1 Expression in Non-small Cell Lung Cancer: A Systematic Review and Meta-analysis.","authors":"Dong Li, Yu Cao, Cheng-Wen Luo, Li-Ping Zhang, Ying-Bo Zou","doi":"10.2174/0115748928265992230925053308","DOIUrl":"10.2174/0115748928265992230925053308","url":null,"abstract":"<p><strong>Background: </strong>The results of the association between aldehyde dehydrogenase 1 (ALDH1) expression and prognosis of non-small cell lung cancer (NSCLC) are contradictory. We conducted this meta-analysis to investigate the clinical significance and prognostic value of ALDH1 in NSCLC.</p><p><strong>Methods: </strong>The databases PubMed, Web of Science, EMBASE, the Cochrane Library, Wanfang, and CNKI were systematically queried to identify eligible studies. The retrieval time was from database establishment to August 2023. We evaluated the correlation between ALDH1 expression and clinical features of NSCLC by employing odds ratios (ORs) and 95% confidence intervals (95% CIs). In addition, we used hazard ratios (HRs) and 95% CIs to evaluate the role of ALDH1 expression in the prognosis of NSCLC.</p><p><strong>Results: </strong>Our study included 21 literatures involving 2721 patients. The expression of ALDH1 in NSCLC was higher than that in normal tissues (OR = 6.04, 95% CI: 1.25-29.27, P = 0.026). The expression of ALDH1 was related to TNM stage (OR = 1.81, 95% CI: 1.06-3.09, P = 0.029), tumor grade (OR = 0.29, 95% CI: 0.17-0.48, P < 0.0001), lymph node metastasis (OR = 2.60, 95% CI: 1.52-4.45, P = 0001) and histological subtype (OR = 0.67, 95% CI: 0.52-0.86, P = 0.002). In patients with NSCLC, we found that the over-expression of ALDH1 was significantly associated with poor overall survival (OS) (HR = 1.44, 95% CI: 1.15-1.81, P = 0.002) and disease-free survival (DFS) (HR = 1.74, 95% CI: 1.45-2.10, P < 0.0001).</p><p><strong>Conclusion: </strong>The expression of ALDH1 is closely associated with the clinicopathologic characteristics and prognosis of NSCLC. ALDH1 may serve as a valuable clinical assessment tool and prognostic predictor in NSCLC.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"599-609"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41224379","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":"Targeted Regulation of Osteoblasts and Osteoclasts in Osteosarcoma Patients by CSF3R Receptor Inhibition of Osteolysis Caused by Tumor Inflammation Based on Transcriptional Spectrum Analysis and Drug Library Screening.","authors":"Wei Duan, Yu Chen, Jinlu Shan, Qian Li","doi":"10.2174/0115748928259095231010055507","DOIUrl":"10.2174/0115748928259095231010055507","url":null,"abstract":"<p><strong>Background: </strong>Osteosarcoma (OS) is a common primary malignant bone tumor that mainly occurs in children and adolescents. The use of IL-8 inhibitor compounds has been reported in patents, which can be used to treat and/or prevent osteosarcoma, but the pathogenesis of osteosarcoma remains to be investigated. At present, osteoblasts and osteoclasts play an important role in the occurrence and development of OS. However, the relationship between osteoblasts and osteoclasts in the specific participation mechanism and inflammatory response of OS patients has not been further studied.</p><p><strong>Methods: </strong>The transcriptome, clinical data, and other data related to OS were downloaded from the GEO database to analyze them with 200 known inflammatory response genes. We set the screening conditions as p < 0.05 and | log₂FC| > 0.50, screened the differentially expressed genes (DEGs) related to OS, tested the correlation coefficient between the OS INF gene and clinical risk, and analyzed the survival prognosis. We further enriched and analyzed the DEGs and inflammatory response genes of OS with GO/KEGG to explore the potential biological function and signal pathway mechanism of OS inflammatory response genes. Moreover, the virtual screening of drug sensitivity of OS based on the FDA drug library was also carried out to explore potential therapeutic drugs targeted to regulate OS osteogenesis and osteoclast inflammation, and finally, the molecular dynamics simulation verification of OS core protein and potential drugs was carried out to explore the binding stability and mechanism between potential drugs and core protein.</p><p><strong>Results: </strong>Through differential analysis of GSE39058, GSE36001, GSE87624, and three other data sets closely related to OS osteoblasts and osteoclasts, we found that there was one upregulated gene (CADM1) and one down-regulated gene (PHF15) related to OS. In addition, GSEA enrichment analysis of the DEGs of OS showed that it was mainly involved in the progress of OS through biological functions, such as oxidative photosynthesis, acute junction, and epithelial-mesenchymal transition. The enrichment analysis of OS DEGs revealed that they mainly affect the occurrence and progress of OS by participating in the regulation of the actin skeleton, PI3K Akt signal pathway, complement and coagulation cascade. According to the expression of CSF3R in OS patients, a risk coefficient model and a diagnostic model were established. It was found that the more significant the difference in the CSF3R gene in OS patients, the greater the risk coefficient of disease (p < 0.05). The AUC under the curve of the CSF3R gene was greater than 0.65, which had a good diagnostic significance for OS. The above results showed that the prognosis risk gene CSF3R related to OS inflammation was closely related to the survival status of OS patients. Finally, through the virtual screening of the ZINC drug library and molecu","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"635-651"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159667","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":"Upregulation of M6A Reader HNRNPA2B1 Associated with Poor Prognosis and Tumor Progression in Lung Adenocarcinoma.","authors":"Wei Wang, Shengwei Li","doi":"10.2174/0115748928258696230925064550","DOIUrl":"10.2174/0115748928258696230925064550","url":null,"abstract":"<p><strong>Background: </strong>Lung cancer is the most prevalent malignancy worldwide, and lung adenocarcinoma (LUAD) accounts for a substantial proportion of all cases. N6-methyladenosine (m6A) is the most frequent post-transcriptional modification in mRNAs that also plays a role in cancer development. Heterogeneous nuclear ribonucleoprotein A2/B1 (HNRNPA2B1) is a reader of m6A modification, which can affect tumor invasion, migration, and proliferation.</p><p><strong>Objectives: </strong>The purpose of this study was to explore the prognostic factors of LUAD based on m6A through bioinformatics analysis.</p><p><strong>Materials and methods: </strong>The expression levels and prognostic significance of HNRNPA2B1 in LUAD were analyzed on the basis of data extracted from the UALCAN, GEPIA, NCBI-GEO, Human Protein Atlas, STRING, miRDB, TargetScan, PROMO, Starbase, UCSC Xena browser, TIMER, and TISIDB databases. HNRNPA2B1 protein and mRNA levels in several LUAD cell lines were detected by western blotting and qRT-PCR. CCK8, wound-healing and transwell assays were performed to evaluate the proliferation, invasion, and migration abilities of LUAD cells.</p><p><strong>Results: </strong>HNRNPA2B1 mRNA was found to be significantly overexpressed in LUAD tissues, and its high levels correlated with poor OS and DFS. The genes co-expressed with HNRNPA2B1 were related to mRNA production, cell cycle, and histone binding. To determine the mechanistic basis of HNRNPA2B1 in LUAD, we next predicted the microRNAs and transcription factors that were directly associated with HNRNPA2B1, as well as copy number changes. In addition, it was found that HNRNPA2B1 expression was significantly related to CD⁴⁺ T cells, neutrophils, lymphocytes, immunomodulators, and chemokines. Besides, knocking down HNRNPA2B1 in the LUAD cells led to a significant reduction in their proliferation, invasion, and migration rates <i>in vitro</i>.</p><p><strong>Conclusion: </strong>Elevated HNRNPA2B1 is a risk factor in LUAD and portends a poor prognosis.</p>","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":" ","pages":"652-665"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50159675","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":"Patent Selections","authors":"","doi":"10.2174/157489281501200401134340","DOIUrl":"https://doi.org/10.2174/157489281501200401134340","url":null,"abstract":"","PeriodicalId":94186,"journal":{"name":"Recent patents on anti-cancer drug discovery","volume":"5 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2020-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141204953","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}