Drug Development Research最新文献

{"title":"Chitosan-coated nanoparticles in innovative cancer bio-medicine","authors":"Niloufar Rezaei,&nbsp;Ibrahim Zarkesh,&nbsp;Alireza Fotouhi,&nbsp;Hani Keshavarz Alikhani,&nbsp;Moustapha Hassan,&nbsp;Massoud Vosough","doi":"10.1002/ddr.22189","DOIUrl":"https://doi.org/10.1002/ddr.22189","url":null,"abstract":"<p>In the recent decade, nanoparticles (NPs) have had enormous implications in cancer biomedicine, including research, diagnosis, and therapy. However, their broad application still faces obstacles due to some practical limitations and requires further development. Recently, there has been more interest in the coated class of nanoparticles to address those challenges. Chitosan-coated NPs are simple to produce, biodegradable, biocompatible, exhibit antibacterial activity, and have less cytotoxicity. This study provides an updated and comprehensive overview of the application of chitosan-coated NPs as a promising class of NPs in cancer biomedicine. Additionally, we discussed chitosan-coated lipid, metal, and polymer-based nanoparticles in biomedical applications. Furthermore, different coating methods and production/characterization procedures were reviewed. Moreover, the biological and physicochemical advantages of chitosan-coated NPs, including facilitated controlled release, greater physicochemical stability, improved cell/tissue interaction, and enhanced bioavailability of medications, were highlighted. Finally, the prospects of chitosan-coated NPs in cancer biomedicine were discussed.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808152","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":"Comparisons of successful and failed Phase III trials of drugs and biologicals tested for mitigation of oral mucositis in patients being treated with radiotherapy with or without concomitant chemotherapy for cancers of the head and neck","authors":"Lang Liang,&nbsp;Stephen T. Sonis","doi":"10.1002/ddr.22188","DOIUrl":"https://doi.org/10.1002/ddr.22188","url":null,"abstract":"<p>Oral mucositis (OM) remains a significant toxicity among patients being treated with radiotherapy (RT) alone or with concomitant chemotherapy (CRT) for cancers of the head and neck (HNC). Given its clinical significance as an unmet need and its potential commercial viability, the pharmaceutical industry has been actively pursuing an effective intervention. Despite this interest and activity, only a few agents have been studied in Phase III trials (<i>n</i> = 6). The objective of this study was to identify common features that differentiate successful and failed Phase III OM trials. We used the United States Patent and Trademark Office Patent Public Search database to search patents with “oral mucositis” in the claims. We then searched ClinicalTrials.gov and PubMed to determine if Phase III or Phase II trial data for identified biologics/drugs had been published. We assessed each Phase III and Phase II trial for characteristics that may be associated with trial success or failure. We considered a study as a “success” if the primary endpoint reached statistical significance, and we considered a study as “failure” if the primary endpoint did not reach statistical significance. Of the three successful Phase III trials, one investigated avasopasem manganese (Galera Therapeutics) and two examined palifermin (Amgen). The three failed trials included those evaluating dusquetide (Soligenix), iseganan hydrochloride (IntraBiotics Pharmaceuticals), and clonidine (Monopar Therapeutics). We found that differences in the level of sponsor funding, patient inclusion criteria including radiation source and concomitant chemotherapy regimen, and concordance of primary efficacy outcomes between Phase II and Phase III trials influenced outcomes. To properly design clinical trials for OM in HNC patients, it is important that researchers and sponsors take note of specific study characteristics associated with success or failure, particularly with Phase III trials where the risks and costs are the highest.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808153","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":"Anti-NSCLC role of SCN4B by negative regulation of the cGMP-PKG pathway: Integrated utilization of bioinformatics analysis and in vitro assay validation","authors":"Xiujun Yang,&nbsp;Qun Liu,&nbsp;Gang Li","doi":"10.1002/ddr.22192","DOIUrl":"https://doi.org/10.1002/ddr.22192","url":null,"abstract":"<p>Non-small cell lung cancer (NSCLC) is a malignant tumor with low overall cure and survival rates. Uncovering abnormally expressed genes is significantly important for developing novel targeted therapies in NSCLC. This study aimed to discover new differentially expressed genes (DEGs) of NSCLC. The DEGs of NSCLC were identified in eight data sets from Gene Expression Omnibus (GEO) database. The expression profiles and the prognostic significance of SCN4B in LUAD and LUSC were analyzed using GEPIA database. LinkedOmics was used to identify co-expressed genes with SCN4B, which were further subjected to KEGG pathway enrichment analysis. SCN4B-overexpressing plasmid (pcDNA/SCN4B) was transfected into A549 and NCI-H2170 cells to elevate the expression of SCN4B. MTT and TUNEL assays were performed to evaluate cell viability and apoptosis. Relying on the screened DEGs from GEO database, we identified that SCN4B was significantly downregulated in LUAD and LUSC. We confirmed the downregulation of SCN4B in NSCLC tissues using GEPIA database. SCN4B has a prognostic value in LUAD, but not LUSC. KEGG pathway enrichment analysis of SCN4B-related genes showed that cGMP-PKG signaling pathway might be involved in the role of SCN4B in NSCLC. Overexpression of SCN4B in A549 and NCI-H2170 cells inhibited the cell viability. Besides, SCN4B overexpression induced apoptosis of A549 and NCI-H2170 cells. SCN4B inhibited the expression of PKG1 and p-CREB in NSCLC cells. Moreover, the inhibitory effects of SCN4B on tumor malignancy were attenuated by the activator of PKG. In conclusion, integrated bioinformatical analysis proved that SCN4B was downregulated and had a prognostic significance in NSCLC. In vitro experimental studies demonstrated that SCN4B regulated NSCLC cells viability and apoptosis via inhibiting cGMP-PKG signaling pathway.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140808154","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":"Upregulation of FGF9 and NOVA1 in cancer-associated fibroblasts promotes cell proliferation, invasion and migration of triple negative breast cancer","authors":"Bo Zhang,&nbsp;Yang Liu,&nbsp;Jinsong Yu,&nbsp;Xi Lin","doi":"10.1002/ddr.22185","DOIUrl":"https://doi.org/10.1002/ddr.22185","url":null,"abstract":"<p>Cancer-associated fibroblasts (CAFs) play a pivotal role in cancer progression. This study aimed to explore the roles of CAFs-derived Fibroblast growth factor 9 (FGF9) and Neuro-oncological ventral antigen 1 (NOVA1) in triple negative breast cancer (TNBC) progression. MDA-MB-231 and BT-549 cells were cocultured with CAF conditioned-medium (CAF-CM) or normal fibroblasts conditioned-medium (NF-CM). MTT, EdU, colony formation, wound healing, transwell migration, and invasion assays were employed to determine cell proliferation, migration and invasion, respectively. Western blot and RT-qPCR were carried out to examine the protein and mRNA expression of FGF9 and NOVA1. Xenograft tumor experiments were conducted to evaluate the effects of CAFs, FGF9, and NOVA1 on tumor growth in vivo. Our results showed that CAFs significantly promoted the proliferation, invasion, and migration of TNBC cells. FGF9 and NOVA1 were significantly upregulated in TNBC CAFs, tissues and cells. CAF-CM also could increase the expression of FGF9 and NOVA1 in TNBC cells. Knockdown of FGF9 or NOVA1 could hamper cell proliferation, invasion, migration, and EMT of TNBC cells. Moreover, CAFs with FGF9/NOVA1 knockdown also could inhibit TNBC progression. Besides, CAFs significantly accelerated tumor growth in vivo, which was blocked by FGF9/NOVA1 knockdown in nude mice. In conclusion, our results indicated the tumor-promoting role of CAFs in TNBC progression. FGF9 and NOVA1 upregulation in CAFs induced cell proliferation, migration and invasion in vitro, and facilitated tumor growth in vivo in TNBC development.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140641911","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":"Synthesis, docking study, and antitumor evaluation of benzamides and oxadiazole derivatives of 3-phenoxybenzoic acid as VEGFR-2 inhibitors","authors":"Mohammad H. Heriz,&nbsp;Ammar A. R. Mahmood,&nbsp;Salem R. Yasin,&nbsp;Khaled M. Saleh,&nbsp;Mai F. AlSakhen,&nbsp;Sana I. Kanaan,&nbsp;Nisreen Himsawi,&nbsp;Abdulrahman M. Saleh,&nbsp;Lubna H. Tahtamouni","doi":"10.1002/ddr.22186","DOIUrl":"https://doi.org/10.1002/ddr.22186","url":null,"abstract":"<p>Current chemotherapeutic agents have several limitations, including lack of selectivity, the development of undesirable side effects, and chemoresistance. As a result, there is an unmet need for the development of novel small molecules with minimal side effects and the ability to specifically target tumor cells. A new series of 3-phenoxybenzoic acid derivatives, including 1,3,4-oxadiazole derivatives (<b>4a–d</b>) and benzamides derivatives (<b>5a–e</b>) were synthesized; their chemical structures were confirmed by Fourier-transform infrared spectroscopy, ¹H nuclear magnetic resonance (NMR), ¹³C NMR, and mass spectra; and various physicochemical properties were determined. The antiproliferative activities of the new derivatives were evaluated by means of the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Three compounds (<b>4b</b>, <b>4c</b>, and <b>4d</b>) exhibited cytotoxicity against two of the three cell lines tested, five compounds (<b>3</b>, <b>4a</b>, <b>5a</b>, <b>5b</b>, and <b>5e</b>) were toxic to one cell line, while two compounds (<b>5c</b> and <b>5d</b>) were not cytotoxic to any of the three cell lines tested in the current study. Based on docking scores, MTT assay findings, and vascular endothelial growth factor receptor 2 (VEGFR-2) kinase activity data, Compound <b>4d</b> was selected for further biological investigation. Flow cytometry was used to determine the mode of cell death (apoptosis vs. necrosis) and the effect on cell cycle progression. Compound <b>4d</b> arrested HepG2 hepatocellular carcinoma cells in the G2/M phase and activated both the intrinsic and extrinsic apoptosis pathways. In conclusion, Compound <b>4d</b> has shown promising results for future research as a potent VEGFR-2 tyrosine kinase inhibitor.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22186","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140622653","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro and in silico investigation of FDA-approved drugs to be repurposed against Alzheimer's disease","authors":"Didem Akkaya,&nbsp;Gökçe Seyhan,&nbsp;Suat Sari,&nbsp;Burak Barut","doi":"10.1002/ddr.22184","DOIUrl":"https://doi.org/10.1002/ddr.22184","url":null,"abstract":"<p>Alzheimer's disease (AD), one of the main causes of dementia, is a neurodegenerative disorder. Cholinesterase inhibitors are used in the treatment of AD, but prolonged use of these drugs can lead to serious side effects. Drug repurposing is an approach that aims to reveal the effectiveness of drugs in different diseases beyond their clinical uses. In this work, we investigated in vitro and in silico inhibitory effects of 11 different drugs on cholinesterases. The results showed that trimebutine, theophylline, and levamisole had the highest acetylcholinesterase inhibitory actions among the tested drugs, and these drugs inhibited by 68.70 ± 0.46, 53.25 ± 3.40, and 44.03 ± 1.20%, respectively at 1000 µM. In addition, these drugs are bound to acetylcholinesterase via competitive manner. Molecular modeling predicted good fitness in acetylcholinesterase active site for these drugs and possible central nervous system action for trimebutine. All of these results demonstrated that trimebutine was determined to be the drug with the highest potential for use in AD.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140606466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and investigation of the cholinesterase inhibitory and antioxidant capacities of some novel N'-(quinolin-4-ylmethylene)propanehydrazides against Alzheimer's disease","authors":"Burcu Kilic,&nbsp;Deniz S. Dogruer","doi":"10.1002/ddr.22183","DOIUrl":"https://doi.org/10.1002/ddr.22183","url":null,"abstract":"<p>One of the worst long-term health issues of the past few decades is Alzheimer's disease (AD). Unfortunately, there are currently insufficient choices for treating and caring for AD, which makes it a popular subject for drug development research. Studies on the development of drugs for AD have primarily concentrated on the use of multitarget directed ligands. Following this strategy, we designed new ChE inhibitors with additional antioxidant and metal chelator effects. In this research, eight novel <i>N’</i>-(quinolin-4-ylmethylene)propanehydrazide derivatives were synthesized and characterized. We then evaluated the inhibition potency of all the final compounds for cholinesterase enzymes. Among them, <b>4e</b> (IC₅₀ acetylcholinesterase [AChE] = 0.69 µM and butyrylcholinesterase [BChE]= 26.00 µM) and <b>4h</b> (IC_50's AChE= 7.04 µM and BChE= 16.06 µM) were found to be the most potent AChE and BChE inhibitors, respectively.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.22183","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140559611","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single and multiple inhibitors of the biosynthesis of 5-, 12-, 15-lipoxygenase products derived from cinnamyl-3,4-dihydroxy-α-cyanocinnamate: Synthesis and structure–activity relationship","authors":"Mohamed Touaibia,&nbsp;Audrey Isabel Chiasson,&nbsp;Samuel Robichaud,&nbsp;Jérémie A. Doiron,&nbsp;Mathieu P. A. Hébert,&nbsp;Marc E. Surette","doi":"10.1002/ddr.22181","DOIUrl":"https://doi.org/10.1002/ddr.22181","url":null,"abstract":"<p>The involvement of lipoxygenases in various pathologies, combined with the unavailability of safe and effective inhibitors of the biosynthesis of their products, is a source of inspiration for the development of new inhibitors. Based on a structural analysis of known inhibitors of lipoxygenase products biosynthesis, a comprehensive structure–activity study was carried out, which led to the discovery of several novel compounds (<b>16a</b>-<b>c</b>, <b>17a</b>) demonstrating promising potency to inhibit the biosynthesis of products of 5-, 12- and 15-LO. Compounds <b>16b</b> and <b>16c</b> outperformed zileuton (<b>1</b>), the only FDA-approved 5-LO inhibitor, as well as known inhibitors such as caffeic acid phenethyl ester (CAPE (<b>2</b>)) and cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC (<b>4</b>)). However, the introduction of a cyano group at the α-position of the carbonyl abolished the activity. Compounds <b>16a</b> and <b>17a</b> also inhibited the biosynthesis of 12- and 15-LO products. Compounds <b>16a</b>, <b>17a</b> far surpassed baicalein, a known 12-LO inhibitor, as inhibitors of 12-LO products biosynthesis. Compound <b>17a</b> and CDC (<b>4</b>) showed equivalent inhibition of LO products, proposing that the double bond in the ester moiety is not necessary for the inhibitory activity. The introduction of the cyano group, as in compound <b>17a</b>, at the α-position of the carbonyl in compound <b>16a</b> significantly reduced the inhibitory activity against the biosynthesis of 15-LO products. In addition to the interactions with residues His372 and Phe421 also found with zileuton and CAPE, compounds <b>16a</b> and <b>16c</b> each interact with residue His367 as shown by molecular docking. This new interaction may explain their high affinity with the 5-LO active site.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140552824","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":"YTHDF2 promotes gastric cancer progression and enhances chemoradiotherapy resistance","authors":"Jian Yang,&nbsp;Yawen Chen,&nbsp;Yang He,&nbsp;Mingxu Da","doi":"10.1002/ddr.22179","DOIUrl":"https://doi.org/10.1002/ddr.22179","url":null,"abstract":"<p>The role of YTHDF2 in gastric cancer (GC) is controversial. Due to the limitations of technical difficulty and experimental period, research on completely knocking out YTHDF2 is rare. Therefore, further investigations are still needed to clarify the YTHDF2's clinical significance and biological function in GC. To carry out the investigation, an analysis was performed on the expression levels of YTHDF2 in both publicly available databases and samples obtained from patients with gastric cancer. Based on the complete knockout of YTHDF2 using the CRISPR-Cas9 system, in vivo and in vitro experiments were conducted to analyze the effects of YTHDF2 on tumor formation, radiotherapy and chemoradiotherapy resistance in GC. Our investigation revealed an increase in YTHDF2 levels in GC tissues, which was found to be associated with a negative prognosis. Under hypoxic conditions, high expression of YTHDF2 enhanced the invasion of gastric cancer cells, and high expression of YTHDF2 was associated with HIF-1a. YTHDF2 facilitated gastric cancer cell growth in vitro and in vivo. Moreover, the results of the present study demonstrated that YTHDF2 mediated the expression of CyclinD1 and stability of CyclinD1 mRNA. CyclinD1 knockdown inhibited YTHDF2-mediated GC cell proliferation whereas CyclinD1 overexpression ameliorated YTHDF2 knockdown-induced inhibition of GC progression. Furthermore, YTHDF2 also promoted resistance to DDP and CTX chemotherapy, along with radiotherapy treatment for GC cells. The findings suggested that YTHDF2 expression accelerated GC progression through a potential mechanism involving CyclinD1 expression, and enhanced chemoradiotherapy resistance. This indicated that YTHDF2 could be a promising prognostic biomarker and therapeutic target for individuals diagnosed with GC.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140553129","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":"New insights into the anticancer therapeutic potential of icaritin and its synthetic derivatives","authors":"Octavio Daniel Reyes-Hernández,&nbsp;Gabriela Figueroa-González,&nbsp;Laura Itzel Quintas-Granados,&nbsp;Hector Hernández-Parra,&nbsp;Sheila I. Peña-Corona,&nbsp;Hernán Cortés,&nbsp;Aliya Kipchakbayeva,&nbsp;Zhazira Mukazhanova,&nbsp;Solomon Habtemariam,&nbsp;Gerardo Leyva-Gómez,&nbsp;Dietrich Büsselberg,&nbsp;Javad Sharifi-Rad","doi":"10.1002/ddr.22175","DOIUrl":"https://doi.org/10.1002/ddr.22175","url":null,"abstract":"<p>Icaritin is a natural prenylated flavonoid derived from the Chinese herb Epimedium. The compound has shown antitumor effects in various cancers, especially hepatocellular carcinoma (HCC). Icaritin exerts its anticancer activity by modulating multiple signaling pathways, such as IL-6/JAK/STAT3, ER-α36, and NF-κB, affecting the tumor microenvironment and immune system. Several clinical trials have evaluated the safety and efficacy of icaritin in advanced HCC patients with poor prognoses, who are unsuitable for conventional therapies. The results have demonstrated that icaritin can improve survival, delay progression, and produce clinical benefits in these patients, with a favorable safety profile and minimal adverse events. Moreover, icaritin can enhance the antitumor immune response by regulating the function and phenotype of various immune cells, such as CD8+ T cells, MDSCs, neutrophils, and macrophages. These findings suggest that icaritin is a promising candidate for immunotherapy in HCC and other cancers. However, further studies are needed to elucidate the molecular mechanisms and optimal dosing regimens of icaritin and its potential synergistic effects with other agents. Therefore, this comprehensive review of the scientific literature aims to summarize advances in the knowledge of icaritin in preclinical and clinical studies as well as the pharmacokinetic, metabolism, toxicity, and mechanisms action to recognize the main challenge, gaps, and opportunities to develop a medication that cancer patients can use. Thus, our main objective was to clarify the current state of icaritin for use as an anticancer drug.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140343088","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}