Drug Development Research最新文献

{"title":"Unraveling the Role of Repurposed Drugs in the Treatment of Acne: Success so Far and the Road Ahead","authors":"Popat S. Kumbhar,&nbsp;Vikas Kamble,&nbsp;Kaustubh Ajit Kolekar,&nbsp;Sukriti Vishwas,&nbsp;Pranav Kumbhar,&nbsp;Kalpana S. Patil,&nbsp;Gaurav Gupta,&nbsp;Pankaj M. Kharabe,&nbsp;Manisha Singh,&nbsp;Shailendra Gurav,&nbsp;Dinesh Kumar Chellappan,&nbsp;Sachin Kumar Singh,&nbsp;Kamal Dua,&nbsp;John Disouza,&nbsp;Vandana Patravale","doi":"10.1002/ddr.70057","DOIUrl":"https://doi.org/10.1002/ddr.70057","url":null,"abstract":"<div>\u0000 \u0000 <p>Acne is a skin disease that impacts 9.4% of the world's population. Available treatments for managing acne include retinoid-like drugs, antibiotics, corticosteroids, photo, and radiotherapy. Howevere, the aforementioned treatments have certain limitations such as possibility of developing skin cancer from tetracycline, doxycycline, and corticosteroids, microbial resistance to antibiotics, and deadly side effects, and so forth. Repurposing of existing therapeutics having excellent safety profile can be promising way to treat acne efficiently. The repurposed drugs and phytoceuticals from diverse classes have demonstrated promising effects in treating acne. These repurposed drugs have displayed antiacne effectiveness by targeting single or multiple signaling pathways. Various repurposed therapeutics undergoing clinical trials at different phases demonstrated their safety and efficacy in treating acne. Despite being a very good, safe, and less time-consuming strategy, drug repurposing (DR) faces multiple challenges such as lack of regulatory guidelines, preservation of intellectual property, and clinical validation of claimed therapeutic indication. DR appears to be a viable approach and is likely to offer effective treatment at a reasonable cost in alleviating acne.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380756","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":"Assessment of Antidiarrheal Effect of Oleuropein Through µ-Oopioid Receptor Interaction Pathway: In Vivo and in Silico Studies","authors":"Nishat Jahan,&nbsp;Manoj Mandal,&nbsp;Imam Hossen Rakib,&nbsp;Md. Sakib Al Hasan,&nbsp;Emon Mia,&nbsp;Md. Arif Hossain,&nbsp;Noshin Tasnim Yana,&nbsp;Siddique Akber Ansari,&nbsp;Mehedi Hasan Bappi,&nbsp;Ali Mohamod Wasaf Hasan,&nbsp;Md Abu Sayeed,&nbsp;Muhammad Torequl Islam","doi":"10.1002/ddr.70064","DOIUrl":"https://doi.org/10.1002/ddr.70064","url":null,"abstract":"<div>\u0000 \u0000 <p>Oleuropein (OLP), a compound predominantly found in olive leaves, has been known for its numerous biological activities, including antioxidant, anti-inflammatory, and antimicrobial properties. Despite its established therapeutic potential, its role in treating diarrhea has not been extensively explored. This study aimed to evaluate the antidiarrheal effects of OLP in an in vivo model and to investigate its molecular interactions using <i>in silico</i> docking studies, pharmacokinetic predictions, and toxicity analysis. In the in vivo study, castor oil was used to induce diarrhea in 3-day-old chicks, and the antidiarrheal effect of OLP was tested at doses of 10 and 20 mg/kg. The standard drug, loperamide (LOP) at 3 mg/kg, was used for comparison. The results showed that OLP at both doses significantly (<i>p</i> &lt; 0.05) reduced diarrheal secretions and increased latency, with the 20 mg/kg dose demonstrating the most effective results. The combination of OLP (20 mg/kg) with LOP (3 mg/kg) further enhanced the antidiarrheal effect. In the <i>in silico</i> study, molecular docking revealed that both OLP and LOP exhibited strong binding affinities (BAs) to the key receptor, μ-opioid receptor associated with diarrhea, while OLP showed higher BA (‒8.9 kcal/mol) compared to LOP (‒8.7 kcal/mol). Pharmacokinetic analysis of OLP revealed favorable properties and toxicity studies revealed no acute toxicity, with an LD₅₀ of 2000 mg/kg. In conclusion, the findings suggest that OLP possesses significant antidiarrheal potential both in vivo and through receptor interaction, positioning it as a promising natural therapeutic agent for managing diarrhea. Further studies are warranted to fully elucidate its mechanisms of action and clinical applicability.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143380171","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":"RETRACTION: to “Oleanolic Acid Reduces Oxidative Stress and Neuronal Apoptosis After Experimental Subarachnoid Hemorrhage by Regulating Nrf2/HO-1 Pathway”","authors":"","doi":"10.1002/ddr.70063","DOIUrl":"https://doi.org/10.1002/ddr.70063","url":null,"abstract":"<p>Han, Y., C. Wang, X. Li, and G. Liang. 2022. “Oleanolic Acid Reduces Oxidative Stress and Neuronal Apoptosis After Experimental Subarachnoid Hemorrhage by Regulating Nrf2/HO-1 Pathway.” <i>Drug Development Research</i> 83, no. 3: 680–687. https://doi.org/10.1002/ddr.21899.</p><p>The above article, published online on November 24, 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Il Jeon; and Wiley Periodicals LLC. A third party reported that this article had re-used western blot bands between Figure 4A in this article and another article by some of the same authors (Han et al. 2017 [https://doi.org/10.1016/j.ejphar.2020.173811]). The report also found that this article had duplicated all TUNEL staining images in Figure 4D from that same publication. The authors responded to an inquiry by the publisher, provided what was labeled as original data for the western blots in Figure 4A, and stated that the two studies had been conducted simultaneously and that the images had been mistakenly reused. The authors also claimed that the results of the TUNEL staining experiments were consistent between both studies, but they did not supply original data for the TUNEL staining experiments. Lastly, the authors reported that they had re-performed some experiments.</p><p>An investigation by the publisher and the journal determined that the duplicated western blots showed discrepancies in contrast and included the removal of one band shown in the prior publication. The authors' response also raised concerns over the data integrity practices employed by the authors. As such, the retraction has been agreed on because the evidence of image duplication and concerns over the experimental design and data integrity fundamentally compromise the parties' confidence in the results presented in the article. The authors did not respond to our notice regarding the retraction.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70063","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248824","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":"Design, Synthesis and Molecular Docking of New Thieno[2,3‑d]Pyrimidin-4-One Derivatives as Dual EGFR and FGFR Inhibitors","authors":"Sara Sultan,&nbsp;Samar S. Tawfik,&nbsp;Khalid B. Selim,&nbsp;Magda N.A. Nasr","doi":"10.1002/ddr.70061","DOIUrl":"https://doi.org/10.1002/ddr.70061","url":null,"abstract":"<div>\u0000 \u0000 <p>Novel thienopyrimidinone hybrids <b>5–25</b> were developed and synthesized as potential inhibitors of human EGFR and FGFR. The in vitro antiproliferative action of all compounds, towards the human breast tumor cells MDA-MB-231 and MCF-7, was evaluated with doxorubicin serving as a reference (IC₅₀ = 6.72 µM). Compound <b>23</b> demonstrated the highest anti-breast cancer efficacy against both cellular lines having IC₅₀ ranging from 2.95 to 3.80 µM. The enzyme inhibition of human EGFR and FGFR by the most active candidates <b>18</b>, <b>21</b>and <b>23–25</b> was further evaluated. Compounds <b>21</b> and <b>25</b> were the best EGFR inhibitors having IC₅₀ values of 0.077 and 0.059 µM, respectively, in comparison to Erlotinib (IC₅₀ = 0.04 µM). In comparison with Staurosporine (IC₅₀ = 0.024 µM), compounds <b>24</b> and <b>25</b> were the most active FGFR inhibitors having IC₅₀ values of 0.055 and 0.029 µM, respectively. The study of molecular docking was carried out among the most active EGFR inhibitors <b>21</b> and <b>25</b> and the most active FGFR inhibitors <b>24</b> and <b>25</b> to examine the relation between the binding pattern of these compounds with EGFR and FGFR catalytic active sites and their biological activity, whereas the computational results were aligned with the biological results. Finally, compound <b>25</b>, which was found to be the best dual inhibitor against EGFR and FGFR, was tested for inducing apoptosis and affecting cellular arrest within G2/M phase as well as it was screened to measure its safety towards normal breast cells MCF10a with IC₅₀ value of 47.16 µM in contrast to the reference Staurosporine (IC₅₀ = 18.86 µM). Accordingly, compound <b>25</b> could be considered as a potential breast cancer therapy.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143248823","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":"Design, Synthesis, Docking Studies, and Investigation of Dual EGFR/VEGFR-2 Inhibitory Potentials of New Pyrazole and Pyrazolopyridine Derivatives","authors":"Shimaa M. Alhamaky,&nbsp;Nadia A. Khalil,&nbsp;Amr K. A. Bass,&nbsp;Nada Osama,&nbsp;Marwa S. A. Hassan","doi":"10.1002/ddr.70056","DOIUrl":"10.1002/ddr.70056","url":null,"abstract":"<div>\u0000 \u0000 <p>The anticancer potential of certain newly synthesized pyrazole and pyrazolopyridine derivatives has been estimated. NCI 60 cancer cells cytotoxic screening pointed out compounds <b>3e</b> and <b>3f</b> as the highest cytotoxic agents with % mean growth inhibition of 67.69% and 87.34%, respectively. The five dose outcomes outlined <b>3f</b> as the most potent cytotoxic agent with promising MG-MID GI₅₀ = 3.3 µM when compared to erlotinib (MG-MID GI₅₀ = 7.68 µM). In the in vitro assays, compounds <b>3d, 3e, 3f,</b> and <b>4a</b> demonstrated dual inhibitory potential on EGFR^WT and VEGFR-2 with IC₅₀ range of 0.066−0.184 µM and 0.102−0.418 µM, respectively. The best dual EGFR/VEGRF-2 inhibitory effect was shown by the compound <b>3f</b>. Moreover, the latter compound stopped the cell cycle at the G1/S phase. Also, it greatly boosted total apoptosis, including early and late apoptosis, by 54.5- and 84.7-fold, respectively, which supposes HCT-116 cell death via inducing apoptosis. This was confirmed by the elevation of the BAX and caspase-3 levels, and the decreased BCL-2 level. Moreover, the safety of the most active compound <b>3f</b> was assessed and the results showed promising selectivity of compound <b>3f</b> toward HCT-116 over FHC (selectivity index [SI]: 20.84) when compared to erlotinib (SI: 3.42). Finally, compound <b>3f</b> demonstrated efficient binding to both EGFR and VEGFR-2 enzymes, which could explain the sufficient inhibition level of each enzyme.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188424","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":"Experimentation of Heterocycles (2013-22) as Potent Pharmacophores in Drug Design of Multiple Sclerosis","authors":"Atukuri Dorababu","doi":"10.1002/ddr.70059","DOIUrl":"10.1002/ddr.70059","url":null,"abstract":"<div>\u0000 \u0000 <p>Multiple sclerosis (MS) is a demyelinating disease in which the insulating cover (myelin sheath) of the brain and spinal cord is damaged. Demyelination results in a decreased signal transmission in the nervous system. Symptoms include double vision, muscle weakness, and difficulty with coordination. Genetic and viral infections have been proposed as plausible factors responsible for MS. Although there is no cure for MS, treatment prevents future attacks. At present, chemotherapy and monoclonal antibodies are the available treatments for MS. Heterocyclic compounds are currently being tested clinically for their efficacy. Some heterocyclic scaffolds have been found to be promising for the treatment of MS. In view of this, research has been conducted towards the design and discovery of chemical agents for MS. Hence, the literature relevant to drug design for MS in the last decade has been collated and described comprehensively so that it would be helpful for efficient drug design for MS in the future. Additionally, through the structure–activity relationship, the importance of crucial structural features was emphasized. The classification was primarily based on the type of heterocycle.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188444","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":"Discovery of Hydrazine Clubbed Thiazoles as Potential Antidiabetic Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies","authors":"Betül Kaya,&nbsp;Hakan Tahtacı,&nbsp;Bilge Çiftçi,&nbsp;Hatice Esra Duran,&nbsp;Adem Necip,&nbsp;Mesut Işık,&nbsp;Şükrü Beydemir","doi":"10.1002/ddr.70060","DOIUrl":"10.1002/ddr.70060","url":null,"abstract":"<p>In this study, hydrazine clubbed thiazole derivatives (<b>3a</b>–<b>3j</b>) were obtained by Hantzsch thiazole synthesis and characterized by MS, ¹H NMR, and ¹³C NMR. The inhibitory potentials of the derivatives against diabetes-related enzymes such as aldose reductase (AR), α-glycosidase (α-GLY), and α-amylase (α-AMY) were experimentally determined, and the results were supported by molecular docking. The results showed that the derivatives (<b>3a</b>–<b>3j</b>) displayed varied degree of potential inhibitory activity, with <i>K</i>_I values covering the following ranges: 5.47 ± 0.53 to 23.89 ± 1.46 nM for AR and 1.76 ± 0.01 to 24.81 ± 0.15 μM for α-GLY, and with IC₅₀ values 4.94–28.17 μM for α-AMY, as compared to standard epalrestat and acarbose (<i>K</i>_I: 34.53 ± 2.52 nM for AR and 23.53 ± 2.72 μM for α-GLY, respectively). The selective activity of these derivatives on antidiabetic enzymes may be important for the treatment of diabetes and may lead to the development of alternative new compounds for this purpose.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70060","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143188428","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":"Andrographolide Mitigates Cisplatin Resistance by Inhibiting SPP1 Regulated NF-kB/iNOS/COX-2 and PI3K/AKT Pathway in Cisplatin Resistant Cervical Carcinoma Cells","authors":"Akbar Pasha,&nbsp;Doneti Ravinder,&nbsp;Smita C. Pawar","doi":"10.1002/ddr.70052","DOIUrl":"10.1002/ddr.70052","url":null,"abstract":"<div>\u0000 \u0000 <p>Drug resistance and cancer recurrence are major cause of Cervical cancer (CC) patient mortality. Cisplatin (CDDP) is the major drug that has been extremely used in all stages in treating CC, although relapse and malignant instances have been observed as a result of cisplatin resistance in CC. In the present study, we established Cisplatin resistant CC HeLa cell line model and the cytotoxic effects of Andro as a single agent or in combination with CDDP were investigated to assess its potential as a chemotherapeutic agent in cisplatin-resistant HeLa (CisR-HeLa) cells. Andro enhanced the cytotoxicity of CDDP in CisR-HeLa cells and shown a synergistic effect by reducing cell viability, proliferation, migration, invasion, and inducing apoptosis in cisplatin resistant cells. Furthermore, we evaluated the expression levels of inflammatory and oncogenic proteins, SPP1, NF-kB, iNOS, COX-2, and the PI3K/AKT signaling pathway, which are associated with cisplatin resistance, as well as using Andro to regulate the targeted markers in CisR-HeLa cells to overcome resistance. The results show that suppressing SPP1 and NF-kB by Andro alone or in combination with CDDP regulates iNOS, COX-2, and increases PTEN expression. The addition of Andro to CDDP inhibited PI3K and AKT expression as well as triggered synergistic apoptosis, which could be associated with variations in Bax and Bcl-2 protein levels. The results suggest that Andro in combination with CDDP exhibits synergistic anti-tumor growth efficacy that targets multiple inflammatory markers, resulting in a promising treatment option for individuals with recurrent cancer due to drug resistance and advanced CC.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064046","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":"Antileishmanial and Antitrypanosomal Trends of Synthetic Tetralone Derivatives","authors":"Abdulsalam A. M. Alkhaldi,&nbsp;Harry P. de Koning,&nbsp;Syed Nasir Abbas Bukhari","doi":"10.1002/ddr.70055","DOIUrl":"10.1002/ddr.70055","url":null,"abstract":"<div>\u0000 \u0000 <p>Leishmaniasis and trypanosomiasis are parasitic diseases that are closely linked to poverty, pose significant local burdens, and are common in tropical and subtropical regions. Various synthetic tetralone derivatives were studied as potential scaffolds for antileishmanial and antitrypanosomal activities. The compounds were studied for their effectiveness against multiple kinetoplastid protozoan pathogens: <i>Leishmania major</i>, <i>Leishmania mexicana,</i> and bloodstream trypomastigotes of <i>Trypanosoma brucei brucei</i>. Two different strains of <i>T. b. brucei</i> were used. The first strain was the wild-type <i>Trypanosoma brucei</i> (s427-WT), and the second strain was the multidrug resistant (MDR) strain B48, which was produced by deleting the TbAT1 gene from s427WT and subsequent adaptation to high levels of resistance to diamidines and organo-arsenical drugs. Compounds <b>4c, 7c, 9b</b>, and <b>11b</b> showed activity against two strains of <i>Trypanosoma</i> and two different <i>Leishmania</i> species, establishing them as versatile leads with broad anti-kinetoplastid activity. Compound <b>4c</b>, a tetralone derivative with a bromo-containing trimethoxybenzylidene moiety and methyl-substituted cyclohexanone ring, was identified as the most potent inhibitor for both <i>T. b. brucei</i> strains, with EC₅₀ values of 0.19 and 0.22 µM for WT and B48, respectively, showing the absence of cross-resistance with the diamidine and arsenical trypanocide classes. In addition, compound <b>4c</b> exhibited more potency than both controls, eflornithine and pentamidine, against the MDR strain. We conclude that tetralone derivates could be a valuable starting point for the discovery of new antiparasitic drugs.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057905","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":"Investigating the Impact of B Cell-Related Genes on Colorectal Cancer Immunosuppressive Environment and Immunotherapy Evasion","authors":"Haixia Wu,&nbsp;Yilin Yu,&nbsp;Zhiping Wang,&nbsp;Shiji Wu,&nbsp;Lingdong Shao,&nbsp;Liang Hong,&nbsp;Jianjian Qiu,&nbsp;Xueqing Zhang,&nbsp;Junxin Wu","doi":"10.1002/ddr.70053","DOIUrl":"10.1002/ddr.70053","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>We aimed to elucidate the prognostic and immunological roles of B cell-related genes in colorectal cancer (CRC). This study comprehensively integrated data from single-cell RNA-sequencing, TCGA, GEO, IMvigor210, GDSC, CancerSEA, HPA, and TISIDB databases to explore prognostic implications and immunological significance of B cell-related gene signature in CRC. We identified seven prognostically significant B cell-related genes for constructing a risk score. Clinical relevance analysis indicated that this risk score served as an independent prognostic factor, with the model accurately predicting patient outcomes. GSEA results implicated the risk score in immune function, cell cycle, and DNA replication. Immune infiltration analysis revealing lower levels of B cells, CD4+ cells, and CD8+ cells in the high-risk group, correlating with decreased immune activity and function. IMvigor210 and TIDE analysis indicated poorer prognosis among high-risk group patients receiving immune therapy. Additionally, the high-risk group exhibited lower sensitivity to immune therapy. Further analysis of drug sensitivity suggested higher resistance to common chemotherapy drugs among high-risk groups. Finally, we identified HSPA1A as the gene with the strongest association with immune and inflammatory responses. Validation of HSPA1A protein expression and prognosis demonstrated elevated expression in CRC compared to normal colorectal tissue, further reinforcing its association with poorer prognosis and higher tumor stage. The risk score exhibited substantial variations in clinical characteristics, functional mechanism, TMB, drug sensitivity, immune cell infiltration, and immune subtype. Our findings may aid in clinical decision-making by shedding light on novel and promising biomarkers for CRC prognosis and immunotherapy response prediction.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 1","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045890","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}