Anti-cancer agents in medicinal chemistry最新文献

{"title":"The Dual Role of ADAMTS9-AS1 in Various Human Cancers: Molecular Pathogenesis and Clinical Implications.","authors":"Haodong He, Jingjie Yang, Yan Zhou, Xinyan Zheng, Lihan Chen, Zhujun Mao, Chuyuan Liao, Tongtong Li, Haoran Liu, Gang Zhou, Houdong Li, Chengfu Yuan","doi":"10.2174/0118715206359325241119075640","DOIUrl":"10.2174/0118715206359325241119075640","url":null,"abstract":"<p><p>Long non-coding RNA (lncRNA) is a type of non-coding RNA distinguished by a length exceeding 200 nucleotides. Recent studies indicated that lncRNAs participate in various biological processes, such as chromatin remodeling, transcriptional and post-transcriptional regulation, and the modulation of cell proliferation, death, and differentiation, hence influencing gene expression and cellular function. ADAMTS9-AS1, an antisense long non-coding RNA situated on human chromosome 3p14.1, has garnered significant interest due to its pivotal involvement in the advancement and spread of diverse malignant tumors. ADAMTS9-AS1 functions as a competitive endogenous RNA (ceRNA) that interacts with multiple microRNAs (miRNAs) and plays a crucial role in regulating gene expression and cellular functions by modulating essential signaling pathways, including PI3K/AKT/mTOR, Wnt/β-catenin, and Ras/MAPK pathways. Dysregulation of this factor has been linked to tumor development, migration, invasion, and resistance to apoptotic mechanisms, including as iron-induced apoptosis, underscoring its intricate function in cancer pathology. While current research has clarified certain pathways involved in cancer formation, additional clinical and <i>in vivo</i> investigations are necessary to enhance comprehension of its specific involvement across various cancer types. This review encapsulates the recent discoveries on the correlation of ADAMTS9-AS1 with numerous malignancies, clarifying its molecular mechanisms and its prospective role as a therapeutic target in oncology. Furthermore, it identifies ADAMTS9-AS1 as a potential early diagnostic biomarker and therapeutic target, offering novel opportunities for targeted intervention in oncology.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"533-543"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942992","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":"Emerging Claudin18.2-targeting Therapy for Systemic Treatment of Gastric Cancer: Seeking Nobility Amidst Danger.","authors":"Xueshuai Ye, Yongqiang Wu, Haiqiang Zhang","doi":"10.2174/0118715206329892240927081033","DOIUrl":"10.2174/0118715206329892240927081033","url":null,"abstract":"<p><p>Gastric cancer in advanced stages lacked effective treatment options. claudin18.2 (CLDN18.2) is a membrane protein that is crucial for close junctions in the differentiated epithelial cells of the gastric mucosa, playing a vital role in barrier function, and can be hardly recognized by immune cells due to its polarity pattern. As the polarity of gastric tumor cells changes, claudin18.2 is exposed on the cell surface, resulting in immune system recognition, and making it an ideal target. In this review, we summarized the expression regulation mechanism of claudin18.2 both in normal cells and malignant tumor cells. Besides, we analyzed the available clinical results and potential areas for future research on claudin18.2-positive gastric cancer and claudin18.2-targeting therapy. In conclusion, claudin18.2 is an ideal target for gastric cancer treatment, and the claudin18.2-targeting therapy has changed the treatment pattern of gastric cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"223-231"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142370794","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":"Schisanhenol Inhibits the Proliferation of Hepatocellular Carcinoma Cells by Targeting Programmed Cell Death-ligand 1 <i>via</i> the STAT3 Pathways.","authors":"Zhihong Zhang, Yiwen Zhong, Xu Han, Xueyang Hu, Yuhan Wang, Lei Huang, Siying Li, Ziqing Li, Chunmei Wang, He Li, Jinghui Sun, Wenyue Zhuang, Mengyang Wang, Jianguang Chen, Wei Liu, Chang Liu, Xin Guo, Siyu Yuan, Jiping Wu","doi":"10.2174/0118715206349131241121091834","DOIUrl":"10.2174/0118715206349131241121091834","url":null,"abstract":"<p><strong>Background: </strong>Programmed cell death-ligand 1 (PD-L1) is overexpressed in tumor cells, which promotes tumor cell survival and cell proliferation and causes tumor cells to escape T-cell killing. Schisanhenol, a biphenyl cyclooctene lignin-like compound, was extracted and isolated from the plant named <i>Schisandra rubriflora</i> (Franch.).</p><p><strong>Purpose: </strong>In this work, we studied the anticancer potential of schisanhenol and explored whether schisanhenol mediated its effect by inhibiting the expression of PD-L1 <i>in vitro</i> and <i>in vivo</i>.</p><p><strong>Materials and methods: </strong><i>In vitro</i>, we performed western blot, immunofluorescence, immunoprecipitation, and colony formation assays to study the proteins, genes, and pathways related to the anti-tumour activity of schisanhenol. <i>In vivo</i>, we explored the antitumor activity of schisanhenol through orthotopic liver transplantation and subcutaneous transplantation tumor models of hepatocellular carcinoma (HCC) cells.</p><p><strong>Results: </strong>We found that schisanhenol decreased the viability of HCC cells. It inhibited the expression of programmed cell death ligand-1 (PD-L1), which plays a pivotal role in tumorigenesis. Subsequently, schisanhenol suppressed the expression of PD-L1 by decreasing the activation of STAT3. Furthermore, we found that schisanhenol inhibited the activation of STAT3 <i> via</i> JAK/STAT3 (T705), Src/STAT3 (T705), and PI3K/AKT/mTOR/STAT3 (S727) pathways. Colony formation tests showed that schisanhenol suppressed cell proliferation by inhibiting PD-L1. Schisanhenol also enhanced cytotoxic T lymphocytes (CTL) activity and regained their ability to kill tumour cells in co-culture. Finally, <i>in vivo</i> observation confirmed the antitumor activity of schisanhenol.</p><p><strong>Conclusion: </strong>Schisanhenol inhibits the proliferation of HCC cells by targeting PD-L1 <i> via</i> the STAT3 pathways. These findings prove that schisanhenol is a valuable candidate for HCC therapeutics and reveal previously unknown characteristics of schisanhenol.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"697-710"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982533","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":"Recent Prospectives of Cellular Signaling Role for Mammary Gland Carcinogenesis.","authors":"Monu Kumar Kashyap, Sikma Roy, Shiwani Jaiswal, Shweta Verma, Siddharth Srivastava, Amit Kumar Nigam, Awadhesh Kumar, Bandana Singh, Ved Prakash Tiwari, Mahima Mahima, Akash Ved, Karuna S Shukla, Namrata Singh","doi":"10.2174/0118715206319933241104100736","DOIUrl":"10.2174/0118715206319933241104100736","url":null,"abstract":"<p><p>In women globally, breast cancer ranks as the second most frequent cause of cancer-related deaths, making up about 25% of female cancer cases, which is pretty standard in affluent countries. Breast cancer is divided into subtypes based on aggressive, genetic and stage. The precise cause of the problem is still unknown. However, the following significant risk factors have been found: sex, age, heredity, not having children, breastfeeding, elevated hormone levels, and personal lifestyle. The presence or lack of three nuclear receptors ER, PR, and HER2/ERBB2 (triple negative) and the amplification of the HER2/ErbB2 gene are the clinical criteria used to classify breast cancer. Chemotherapy is still the cornerstone of treatment for triple-negative breast cancer (TNBC), even. If, for the first two groups of patients,receptor-specific therapy is used. The most often prescribed chemotherapy agents for the treatment of breast cancer include doxorubicin (DOX), curcumin paclitaxel (PTX), docetaxel (DCX), thioridazine (THZ), disulfiram (DSF), and camptothecin (CPT). Monoclonal antibodies (mAbs) were used in antibody-drug conjugates (ADCs) to bind tumor-associated target antigens selectively and deliver very effective cytotoxic agents. According to recent research, synthetic derivatives effectively combat both MCF- 7 and breast cancer cell lines that are resistant to many drugs. This review provides a wealth of information on the mechanism of action of synthetic derivatives on multidrug-resistant cell lines. This review includes information about how synthetic derivatives affect cancer cells that have developed multidrug resistance during chemotherapy. These mechanisms have been linked to factors such as increased drug efflux, genetic factors, growth factors, increased DNA repair capacity, and elevated xenobiotic metabolism. Because of this, more research is necessary to learn more about the effectiveness of synthetic derivatives against breast cancer and cell lines that are resistant to several drugs. This review aims to find recent prospects of various types of cellular signaling pathways (JAK/STAT, Akt, MAPK, etc.) involved in the progression of breast cancer disorder, and we also study different synthetic and natural drugs that are applied for treating breast cancer.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"818-840"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142926269","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":"Cytotoxic Effects of <i>Lecaniodiscus Cupanioides</i> (Planch.) Extract and Triterpenoids-derived Gold Nanoparticles On MCF-7 Breast Cancer Cell Lines.","authors":"Roshudufhadzwa Magadani, Derek Tantoh Ndinteh, Saartjie Roux, Louisiane Patrick Nangah, Item Justin Atangwho, Daniel Ejim Uti, Esther Ugo Alum, Simeon Ikechukwu Egba","doi":"10.2174/0118715206325529241004064307","DOIUrl":"10.2174/0118715206325529241004064307","url":null,"abstract":"<p><strong>Background: </strong>The prevalent disease known as breast cancer has a significant impact on both men's and women's health and quality of life.</p><p><strong>Aim: </strong>The aim of this study was to explore the potential roles of <i>Lecaniodiscus cupanioides</i> (planch.) extract and triterpenoid- derived gold nanoparticles (AuNPs) in cancer therapy, specifically targeting MCF-7 breast cancer cell lines.</p><p><strong>Methods: </strong>Gold nanoparticles were synthesized utilizing triterpenoid (ZJ-AuNPs) and leaf extract from <i>Lecaniodiscus cupanioides</i> (LC-AuNPs). Fourier transform infrared spectroscopy (FTIR), Dynamic light scattering (DLS), High-resolution transmission electron microscopy (HRTEM), and UV-vis spectroscopy were employed to characterize the nanoparticles. Additionally, the MTT assay was used to assess the impact of AuNPs on cancer cell viability using MCF-7 breast cancer cell lines.</p><p><strong>Results: </strong>Analysis of ZJ-AuNPs and LC-AuNPs revealed DLS zeta potentials of -31.8 and -35.8 mV, respectively, and a corresponding UV-vis absorption maxima at 540 and 550 nm. Also, the ZJ-AuNPs and LC-AuNPs had respective zeta-sizes that ranged from 25.84 to 35.98 nm and polydispersive index values between 0.2360 and 0.773. Furthermore, the presence of the chemical groups -OH and -NH was shown to be necessary for the green method of capping and reducing the gold nanoparticles. Nevertheless, a significant decrease in cell viability percentages was noted in the MTT experiment, accompanied by an increase in the quantity or concentration of the nanoparticles for both ZJ-AuNPs and LC-AuNPs.</p><p><strong>Conclusion: </strong>Given the data obtained in this study, the biosynthesized ZJ-AuNPs and LC-AuNPs were shown to possess potent cytotoxic effects on breast cancer cells. Hence, they may be valuable tools in the development of new cancer chemotherapy drugs.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"841-850"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143051395","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":"Selected Metal (Au, Ag, and Cu) Complexes of N-heterocyclic Ligands as Potential Anticancer Agents: A Review.","authors":"Meshal Alshamrani","doi":"10.2174/0118715206331002241119145651","DOIUrl":"10.2174/0118715206331002241119145651","url":null,"abstract":"<p><p>Nitrogen-based organic heterocyclic compounds are an important source of therapeutic agents. About 75% of drugs approved by the FDA and currently available in the market are N-heterocyclic organic compounds. The N-heterocyclic organic compounds like pyridine, indole, triazoles, triazine, imidazoles, benzimidazoles, quinazolines, pyrazoles, quinolines, pyrimidines, porphyrin, etc. have demonstrated significant biological activities. These heterocyclic organic compounds also coordinate with various metal ions and form coordination compounds. Most of them have shown improved biological activities. The research on the metal complexes of these compounds reported their significant biological activities. N-heterocyclic-based metal complexes showed outstanding anticancer activities against different cancer cell lines, including VEGFR-2, HT-29, MDA-MB-231, MCF-7 K562, A549, HepG2, HL60, A2780, WI-38, Colo-205, PC-3, and other cancer cell lines. Some of these compounds showed better anticancer activity than cisplatin. In this review, we summarized the anticancer properties of N-heterocyclic-based gold (Au), silver (Ag), and copper (Cu) complexes and explored the mechanisms of action and potential structure-activity relationships (SAR) of these complexes. Our goal is to assist researchers in designing highly potent N-heterocyclic-based Au, Ag, and Cu complexes for the potential treatment of various cancers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"729-740"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142942925","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":"Royal Jelly's Strong Selective Cytotoxicity Against Lung Malignant Cells and Macromolecular Alterations in Cells Observed by FTIR Spectroscopy.","authors":"Ferhunde Aysin","doi":"10.2174/0118715206355400241112084611","DOIUrl":"10.2174/0118715206355400241112084611","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction/objective: &lt;/strong&gt;Several nutraceuticals, food, and cosmetic products can be developed using royal jelly. It is known for its potential health benefits, including its ability to boost the immune system and reduce inflammation. It is rich in vitamins, minerals, and antioxidants, which can improve general health. Royal jelly (RJ) is also being studied as a potential therapeutic agent for cancer and other chronic diseases. It is effective in reducing tumor growth and stimulating immunity.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;In this study, we investigated the effects of royal jelly on cancerous A549 cells and healthy MRC-5 cells at various doses ranging from 1.25 to 10 mg/mL. Royal jelly's anti-proliferative effect was evaluated by MTT and SRB assay for 48 h. The induction of necrosis and apoptosis was assessed by flow cytometry as well. The relative amounts of major molecules in Royal jelly were determined by FTIR spectroscopy to identify key functional groups and molecular structures. In addition, this technique was used for the first time to detect changes in the macromolecular composition of lung cells treated with royal jelly. Thus, it provided insights into the relative abundance of proteins, lipids, and carbohydrates, which could correlate with their bioactive properties.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The antiproliferative effect of Royal jelly was found to be selective on A549 cells in a dose-dependent manner with an IC&lt;sub&gt;50&lt;/sub&gt; of 9.26 mg/mL, with no cytotoxic effects on normal MRC-5 cells. Moreover, Royal jelly induced predominantly necrotic cell death in A549 cells, %39.10 at 4 mg/mL and %57.88 at 10 mg/mL concentrations. However, the necrosis rate in MRC-5 cells was quite low, at 9.16% and 20.44% at the same doses. Royal jelly showed dose-dependent selective cytotoxicity toward A549 cells, whereas it exhibited no apparent cytotoxicity in MRC-5 cells. In order to identify the biomolecular changes induced by royal jelly, we used two unsupervised chemometric pattern recognition algorithms (PCA and HCA) on the preprocessed sample FTIR spectra to determine the effects of royal jelly on cell biochemistry. According to PCA and HCA results, RJ treatments especially affected biomolecules in A549 cells. The total spectral band variances in the PCA loading spectra were calculated for understanding biomolecular alterations. These plots revealed profound changes in the lipid, protein, and nucleic acid content of RJ-applied lung cells, primarily identifying RJ and H&lt;sub&gt;2&lt;/sub&gt;O&lt;sub&gt;2&lt;/sub&gt; treated groups for A549 cells.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Ultimately, the selective cytotoxicity of royal jelly toward A549 cancerous cells suggests that royal jelly may be a promising therapeutic agent for identifying innovative lung cancer treatment strategies. Additionally, understanding the molecular alterations induced by royal jelly could guide the development of novel cancer treatments that exploit its bioactive properties.","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"750-764"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977224","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":"Chlorogenic Acid Ameliorates CCl₄-induced Liver Fibrosis by Modulating the PI3K/AKT/mTOR Autophagy Pathway.","authors":"Amr Negm, Amira Afifi El-Neanaey, Abada El Sayed Khadr, Maher Abd El Naby Kamel, Abd El-Hamid Abdo Ismail, Ibrahim El Tantawy El Sayed, Wael Sobhy Darwish, Mabrouk Attia Abd Eldaim, Raghda Sobhy Okaz, Mohamed Hamdy Bahr, Nihal Almuraikhi, Nermine Beshara, Tamer Mohamed Shawky, Ezat A Mersal","doi":"10.2174/0118715206357043250116063202","DOIUrl":"10.2174/0118715206357043250116063202","url":null,"abstract":"<p><strong>Background: </strong>Liver fibrosis represents a serious risk to global health by impairing quality of life and elevating the chances of hepatocellular carcinoma, while the intricate role of autophagy can either alleviate or worsen fibrosis depending on its functioning.</p><p><strong>Objective: </strong>Herein, we aimed to investigate the therapeutic effect of chlorogenic acid in CCl₄-induced hepatic fibrosis and explored the autophagy pathway as the possible molecular target of chlorogenic acid.</p><p><strong>Methods: </strong>Rats were injected with carbon tetrachloride (1ml/kg) to induce liver fibrosis for 10 weeks. In the current study, the liver fibrosis rats were treated daily with chlorogenic acid (20, 40, and 60 mg/kg) for 30 days. Liver function tests, renal function tests, lipid peroxidation, antioxidant enzyme, anti-inflammatory NF-κB level, and autophagy pathway parameters (PI3K, AKT, mTOR, LC3, and Beclin-1) were assessed.</p><p><strong>Results: </strong>CCl₄ elevated serum AST and ALT activity, and hepatic malondialdehyde, PI3K, AKT, and mTOR expressions. It decreased LC3, Beclin-1 expression, and hepatic glutathione level. The results indicated that chlorogenic acid treatment ameliorated the hepatic functions. It declined serum AST and ALT activities, improved hepatic GSH concentration, decreased lipid peroxidation, and downregulated PI3K, AKT, and mTOR protein expressions in hepatic tissue. Moreover, chlorogenic acid increased the hepatic expression of LC3 and Beclin-1. It also significantly decreased NF-kB expression.</p><p><strong>Conclusion: </strong>Chlorogenic acid showed promise in reducing liver damage in rats caused by CCl₄ by influencing the autophagy process and adjusting levels of antioxidant and inflammatory markers.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"913-920"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021748","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":"A Systematic Review and Meta-analysis on the Safety and Efficacy of CAR T Cell Therapy Targeting GPRC5D in Patients with Multiple Myeloma: A New Insight in Cancer Immunotherapy.","authors":"Behrouz Robat-Jazi, Mehrdad Mahalleh, Mohsen Dashti, Negar Nejati, Mahsa Ahmadpour, Erfan Alinejad, Shiva Mohammadi, Parsa Lorestani, Amir Ali Hamidieh, Mohammad Amin Habibi, Farhad Jadidi-Niaragh","doi":"10.2174/0118715206350342241224073809","DOIUrl":"10.2174/0118715206350342241224073809","url":null,"abstract":"<p><strong>Background: </strong>Despite ongoing advances and introducing innovative therapeutic approaches for the treatment of multiple myeloma (MM), relapses are common, with low overall survival rates. G protein-coupled receptor, class C, group 5, and member D (GPRC5D) has been expressed in several myeloma cell lines and has demonstrated encouraging outcomes results in <i>in-vitro</i> studies as a potential target for immunotherapies.</p><p><strong>Objective: </strong>We aimed to investigate the safety and efficacy of GPRC5D-targeted CAR T cell therapies in MM patients.</p><p><strong>Methods: </strong>On August 24, 2023, the databases of PubMed, Scopus, Embase, and Web of Science were systematically searched for pertinent studies. After completing a two-step title/abstract and full-text screening process, the eligible studies were included.</p><p><strong>Results: </strong>Following the screening of 107 articles, four studies of 130 multiple myeloma patients treated with GPRC5D-targeted CAR T-cell therapy were included. The meta-analyses showed an ORR of 87% (95% CI [81- 93%]), with 74% (95% CI [65-73%]) for those with prior BCMA-targeted therapy and 88% (95% CI [78-99%]) for those without. PR was 25%, VGPR 33%, and CR/sCR 48%, with 65% achieving MRD-negativity. In terms of safety, hematologic AEs were common, with anemia reported in 86% of patients. Non-hematologic common AEs included CRS (83%, 5% grade ≥3) and hypocalcemia (63%, 10% grade ≥3). No significant publication bias was detected.</p><p><strong>Conclusion: </strong>GPRC5D is an active and safe target that shows promising results in the treatment of relapsed and/or refractory (R/R) MM and heavily pretreated patients.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"1017-1028"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143121979","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":"MG132-mediated Suppression of the Ubiquitin-proteasome Pathway Enhances the Sensitivity of Endometrial Cancer Cells to Cisplatin.","authors":"Zhanhu Zhang, Yiqian Ding","doi":"10.2174/0118715206343550240919055701","DOIUrl":"10.2174/0118715206343550240919055701","url":null,"abstract":"<p><strong>Background: </strong>Tumor cell resistance to cisplatin is a common challenge in endometrial cancer chemotherapy, stemming from various mechanisms. Targeted therapies using proteasome inhibitors, such as MG132, have been investigated to enhance cisplatin sensitivity, potentially offering a novel treatment approach.</p><p><strong>Objective: </strong>The aim of this study was to investigate the effects of MG132 on cisplatin sensitivity in the human endometrial cancer (EC) cell line RL95-2, focusing on cell proliferation, apoptosis, and cell signaling.</p><p><strong>Methods: </strong>Human endometrial cancer RL95-2 cells were exposed to MG132, and cell viability was assessed in a dose-dependent manner. The study evaluated the effect of MG132 on cisplatin-induced proliferation inhibition and apoptosis, correlating with caspase-3 activation and reactive oxygen species (ROS) upregulation. Additionally, we examined the inhibition of the ubiquitin-proteasome system and the expression of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and IL-13 during MG132 and cisplatin co-administration.</p><p><strong>Results: </strong>MG132 exposure significantly reduced cell viability in a dose-dependent manner. It augmented cisplatin- induced proliferation inhibition and enhanced apoptosis, correlating with caspase-3 activation and ROS upregulation. Molecular analysis revealed a profound inhibition of the ubiquitin-proteasome system. MG132 also significantly increased the expression of cisplatin-induced pro-inflammatory cytokines, suggesting a transition from chronic to acute inflammation.</p><p><strong>Conclusion: </strong>MG132 enhances the therapeutic efficacy of cisplatin in human EC cells by suppressing the ubiquitin- proteasome pathway, reducing cell viability, enhancing apoptosis, and shifting the inflammatory response. These findings highlighted the potential of MG132 as an adjuvant in endometrial cancer chemotherapy. Further research is needed to explore detailed mechanisms and clinical applications of this combination therapy.</p>","PeriodicalId":7934,"journal":{"name":"Anti-cancer agents in medicinal chemistry","volume":" ","pages":"281-291"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142360951","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}