Biochemical pharmacology最新文献_第10页

The SGLT2 inhibitor dapagliflozin suppresses endothelial cell pyroptosis mediated by the NF-κB/NLRP3 pathway through downregulation of CTSB SGLT2抑制剂dapagliflozin通过下调CTSB抑制NF-κB/NLRP3通路介导的内皮细胞焦亡

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-07 DOI: 10.1016/j.bcp.2025.116857

Quanwei Zhao , Hui Li , Danan Liu , Bo Zhou , Caiwei Gong , Long Chen , Fujun Liao

{"title":"The SGLT2 inhibitor dapagliflozin suppresses endothelial cell pyroptosis mediated by the NF-κB/NLRP3 pathway through downregulation of CTSB","authors":"Quanwei Zhao , Hui Li , Danan Liu , Bo Zhou , Caiwei Gong , Long Chen , Fujun Liao","doi":"10.1016/j.bcp.2025.116857","DOIUrl":"10.1016/j.bcp.2025.116857","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a chronic inflammatory disease, and pyroptosis—a recently discovered pro-inflammatory programmed cell death process—can exacerbate these inflammatory responses. Vascular endothelial cell pyroptosis contributes to AS progression. Cathepsin B (CTSB) is a crucial member of the cysteine protease family found in lysosomes. However, its exact role in vascular endothelial cell pyroptosis remains unclear. Dapagliflozin (DAPA), a sodium–glucose cotransporter-2 (SGLT2) inhibitor, inhibits pyroptosis and alleviates AS independent of its hypoglycemic effect. This study utilized oxidized low-density lipoprotein (ox-LDL) to induce pyroptosis in human umbilical vein endothelial cells (HUVECs) and investigated the effect of this process. The study revealed that ox-LDL induced HUVEC pyroptosis in a concentration-dependent manner, resulting in Na<sup>+</sup> and Ca<sup>2+</sup> overload, lysosomal damage, and increased CTSB release into the cytosol. Lentiviral vectors were used to overexpress or silence CTSB; subsequent analysis revealed that CTSB promotes NLRP3-mediated pyroptosis through nuclear factor κB (NF-κB) activation. Finally, we found that DAPA attenuated HUVEC pyroptosis by inhibiting the NF-κB/NLRP3 pathway and decreasing the expression of CTSB. This effect may be attributed to its ability to alleviate lysosomal damage caused by Na<sup>+</sup>–Ca<sup>2+</sup> overload, thereby reducing CTSB release into the cytosol.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116857"},"PeriodicalIF":5.3,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The function of microRNA related to cancer-associated fibroblasts in pancreatic ductal adenocarcinoma 与癌相关成纤维细胞相关的microRNA在胰腺导管腺癌中的作用

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-06 DOI: 10.1016/j.bcp.2025.116849

Yaohui Fang , Chunlu Tan , Zhenjiang Zheng , Jianchen Yang , Jiali Tang , Ruizhe Guo , Epiphane K. Silli , Zhe Chen , Jia Chen , Ruyu Ge , Yuquan Liu , Xiuqi Wen , Jingdan Liang , Yunfei Zhu , Yutong Jin , Qian Li ([email protected]) , Ying Wang

{"title":"The function of microRNA related to cancer-associated fibroblasts in pancreatic ductal adenocarcinoma","authors":"Yaohui Fang , Chunlu Tan , Zhenjiang Zheng , Jianchen Yang , Jiali Tang , Ruizhe Guo , Epiphane K. Silli , Zhe Chen , Jia Chen , Ruyu Ge , Yuquan Liu , Xiuqi Wen , Jingdan Liang , Yunfei Zhu , Yutong Jin , Qian Li ([email protected]) , Ying Wang","doi":"10.1016/j.bcp.2025.116849","DOIUrl":"10.1016/j.bcp.2025.116849","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor characterized by a poor prognosis. A prominent feature of PDAC is the rich and dense stroma present in the tumor microenvironment (TME), which significantly hinders drug penetration. Cancer-associated fibroblasts (CAFs), activated fibroblasts originating from various cell sources, including pancreatic stellate cells (PSCs) and mesenchymal stem cells (MSCs), play a critical role in PDAC progression and TME formation. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules that are frequently involved in tumorigenesis and progression, exhibiting either oncolytic or oncogenic activity. Increasing evidence suggests that aberrant expression of miRNAs can mediate interactions between cancer cells and CAFs, thereby providing novel therapeutic targets for PDAC treatment. In this review, we will focus on the potential roles of miRNAs that target CAFs or CAFs-derived exosomes in PDAC progression, highlighting the feasibility of therapeutic strategies aimed at restoring aberrantly expressed miRNAs associated with CAFs, offering new pathways for the clinical management of PDAC.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116849"},"PeriodicalIF":5.3,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143576977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The mitochondrial protease ClpP is a promising target for multiple myeloma treatment 线粒体蛋白酶ClpP是多发性骨髓瘤治疗的一个有希望的靶点。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.bcp.2025.116855

Xiang Liu , Jinlong Gu , Song Liu , Jingcao Huang , Linfeng Li , Fangfang Wang , Siyao He , Ziyue Mi , Yue Zhang , Jingjing Wen , Qianwen Gao , Haonan Yang , Yu Feng , Hongmei Luo , Xinyu Zhai , Li Zhang , Yuhuan Zheng , Youfu Luo , Ting Niu

{"title":"The mitochondrial protease ClpP is a promising target for multiple myeloma treatment","authors":"Xiang Liu , Jinlong Gu , Song Liu , Jingcao Huang , Linfeng Li , Fangfang Wang , Siyao He , Ziyue Mi , Yue Zhang , Jingjing Wen , Qianwen Gao , Haonan Yang , Yu Feng , Hongmei Luo , Xinyu Zhai , Li Zhang , Yuhuan Zheng , Youfu Luo , Ting Niu","doi":"10.1016/j.bcp.2025.116855","DOIUrl":"10.1016/j.bcp.2025.116855","url":null,"abstract":"<div><div>Drug resistance and relapse are the major obstacles in multiple myeloma (MM) treatment, driving the search for novel therapeutics. The chemoactivation of mitochondrial caseinolytic protease P (ClpP) has shown to have anticancer effects on many tumors, but has seldom been elucidated in MM.</div><div>Here we found that the CLPP expression was elevated in MM patients, and further increased in relapsed cases. After synthesizing and screening a panel of ClpP agonists, we identified a compound, 7b, as the most potent anti-MM agent in vitro. 7b activated ClpP protease activity, selectively degrading mitochondrial proteins, many of which are involved in oxidative phosphorylation (OXPHOS). As result, 7b treated MM had metabolic dysfunction, the mitochondrial membrane potential (MMP) collapse, reduced OXPHOS levels, and increased mitochondrial reactive oxygen species (ROS), leading to mitophagy-mediated MM cell death. Notably, 7b also showed efficacy against drug-resistant MM cell lines, including bortezomib- and lenalidomide-resistant cells. In vivo, 7b also exhibited remarkable anti-MM activity with tolerable side effects.</div><div>In conclusion, targeting ClpP represents a promising therapeutic strategy for MM, with 7b serving as a potent anti-MM agent, especially for relapsed and refractory MM.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116855"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Inhibitory effects of nimodipine, nitrendipine and felodipine on tamoxifen metabolism and molecular docking 尼莫地平、尼群地平和非洛地平对他莫昔芬代谢和分子对接的抑制作用。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.bcp.2025.116854

Xiaohai Chen, Fengsheng Hong, Yuxin Shen, Hailun Xia, Lu Shi, Zheli Jiang, Ren-ai Xu

{"title":"Inhibitory effects of nimodipine, nitrendipine and felodipine on tamoxifen metabolism and molecular docking","authors":"Xiaohai Chen, Fengsheng Hong, Yuxin Shen, Hailun Xia, Lu Shi, Zheli Jiang, Ren-ai Xu","doi":"10.1016/j.bcp.2025.116854","DOIUrl":"10.1016/j.bcp.2025.116854","url":null,"abstract":"<div><div>Tamoxifen, a selective estrogen receptor modulator (SERM) used in breast cancer therapy, requires metabolic activation by CYP3A4 to exert its biological effects. This study evaluated the effects of calcium channel blockers nimodipine, nitrendipine and felodipine on tamoxifen metabolism by studying their interactions with tamoxifen <em>in vitro</em> and <em>in vivo</em>. Rat liver microsomes (RLM) and human liver microsomes (HLM) were used in this study to evaluate the inhibitory potential of nimodipine, nitrendipine and felodipine on tamoxifen metabolism <em>in vitro</em>. A total of 28 cardiovascular drugs, including calcium channel blockers, were screened in an RLM incubation system <em>in vitro</em>. In RLM, nimodipine, nitrendipine and felodipine had half-maximum inhibitory concentration (IC<sub>50</sub>) values of 5.55 µM, 11.86 µM and 7.71 µM, respectively. In HLM, the IC<sub>50</sub> values were increased to 20.38 µM, 30.06 µM, and 44.45 µM for nimodipine, nitrendipine and felodipine, respectively. The kinetic assays indicated that nimodipine and felodipine inhibited the metabolism of tamoxifen in a competitive way, whereas nitrendipine showed non-competitive inhibition in RLM. However, felodipine exhibited non-competitive inhibition, and nimodipine and nitrendipine showed competitive inhibition in HLM. Pharmacokinetic studies in rats revealed that pretreatment with nimodipine and nitrendipine significantly increased the systemic exposure of tamoxifen, as demonstrated by increasing the area under the curve (AUC), the maximum concentration (C<sub>max</sub>) and decreasing the clearance (CL<sub>z/F</sub>). Finally, molecular docking studies supported these findings, showing potential interactions at the active site of CYP3A4. These results suggested the necessity for careful monitoring and possible dose adjustments of tamoxifen when co-administered with calcium channel blockers in clinic.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116854"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Paeonol enhances a recombinant EGFR-targeted fusion protein-drug conjugate induced antitumor efficacy in esophageal cancer 丹皮酚增强重组egfr靶向融合蛋白-药物偶联物诱导的食管癌抗肿瘤疗效。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-05 DOI: 10.1016/j.bcp.2025.116856

Huaiyu Duan , Yuting Li , Xue Zheng , Junqi Hou , Hongyu Tao , Xiujun Liu , Min Dai , Shiming He

{"title":"Paeonol enhances a recombinant EGFR-targeted fusion protein-drug conjugate induced antitumor efficacy in esophageal cancer","authors":"Huaiyu Duan , Yuting Li , Xue Zheng , Junqi Hou , Hongyu Tao , Xiujun Liu , Min Dai , Shiming He","doi":"10.1016/j.bcp.2025.116856","DOIUrl":"10.1016/j.bcp.2025.116856","url":null,"abstract":"<div><div>Esophageal cancer (EC) is a gastrointestinal cancer with high morbidity and mortality, along with a low 5-year survival rate, which urgently requires the discovery of new drugs for prevention and treatment. Our previous studies have found a novel EGFR-targeted fusion protein-drug conjugate, Fv-LDP-D3-AE, which exhibits significant inhibitory activity against esophageal cancer. However, the effectiveness of monotherapy still faces major challenges in clinical translation for esophageal cancer treatment. Therefore, there is an urgent need to identify a candidate anti-tumor drug that can be combined with Fv-LDP-D3-AE to enhance therapeutic efficacy. In this study, we report a novel combination treatment regimen of paeonol with Fv-LDP-D3-AE, using human esophageal cancer cells KYSE70 and EC109 for <em>in vitro</em> studies and establishing a BALB/c nude mouse xenograft model for <em>in vivo</em> experiments to investigate the anti-tumor efficacy and potential mechanisms of the combination therapy in esophageal cancer. The results indicated that the combined treatment emerged a synergistic effect, which could effectively inhibit the proliferation, migration, and invasion of esophageal cancer cells, induce more obvious cell apoptosis and DNA damage, and suppress tumor growth in the xenograft mouse model with a tumor inhibition rate of 76%. This may be attributed to the combination therapy simultaneously inhibiting the EGFR/AKT/mTOR signaling pathway and downregulating the expression of nucleolin. Overall, these findings suggest that paeonol could synergize with Fv-LDP-D3-AE to enhance anti-esophageal cancer efficacy, which may be a promising therapeutic strategy for esophageal cancer.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116856"},"PeriodicalIF":5.3,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143584454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Therapeutic targets in the Wnt signaling pathway: Treating cancer with specificity Wnt信号通路中的治疗靶点：特异性治疗癌症

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-04 DOI: 10.1016/j.bcp.2025.116848

Jiaxi Zhang , Haochuan Guo , Chengxuan Gong , Jie Shen , Guijie Jiang , Jiarui Liu , Tingming Liang , Li Guo

{"title":"Therapeutic targets in the Wnt signaling pathway: Treating cancer with specificity","authors":"Jiaxi Zhang , Haochuan Guo , Chengxuan Gong , Jie Shen , Guijie Jiang , Jiarui Liu , Tingming Liang , Li Guo","doi":"10.1016/j.bcp.2025.116848","DOIUrl":"10.1016/j.bcp.2025.116848","url":null,"abstract":"<div><div>The Wnt signaling pathway is a critical regulatory mechanism that governs cell cycle progression, apoptosis, epithelial-mesenchymal transition (EMT), angiogenesis, stemness, and the tumor immune microenvironment, while also maintaining tissue homeostasis. Dysregulated activation of this pathway is implicated in various cancers, closely linked to tumor initiation, progression, and metastasis. The Wnt/β-catenin axis plays a central role in the pathogenesis of common cancers, including colorectal cancer (CRC), breast cancer (BC), liver cancer, and lung cancer. Unlike traditional chemotherapy, targeted therapy offers a more precise approach to cancer treatment. As a key regulator of oncogenesis, the Wnt pathway represents a promising target for clinical interventions. This review provides a comprehensive analysis of the Wnt signaling pathway, exploring its roles in tumor biology and its implications in human malignancies. It further examines the molecular mechanisms and modes of action across different cancers, detailing how the Wnt pathway contributes to tumor progression through mechanisms such as metastasis promotion, immune modulation, drug resistance, and enhanced cellular proliferation. Finally, therapeutic strategies targeting Wnt pathway components are discussed, including inhibitors targeting extracellular members, as well as those within the cell membrane, cytoplasm, and nucleus. The potential of these targets in the development of novel therapeutic agents underscores the critical importance of intervening in the Wnt signaling pathway for effective cancer treatment.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116848"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Strategic advancements in targeting the PI3K/AKT/mTOR pathway for Breast cancer therapy 靶向PI3K/AKT/mTOR通路治疗乳腺癌的战略进展。

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-04 DOI: 10.1016/j.bcp.2025.116850

Pankaj Garg , Sravani Ramisetty , Meera Nair , Prakash Kulkarni , David Horne , Ravi Salgia , Sharad S. Singhal

{"title":"Strategic advancements in targeting the PI3K/AKT/mTOR pathway for Breast cancer therapy","authors":"Pankaj Garg , Sravani Ramisetty , Meera Nair , Prakash Kulkarni , David Horne , Ravi Salgia , Sharad S. Singhal","doi":"10.1016/j.bcp.2025.116850","DOIUrl":"10.1016/j.bcp.2025.116850","url":null,"abstract":"<div><div>Breast cancer (BC) is a complex disease that affects millions of women worldwide. Its growing impact calls for advanced treatment strategies to improve patient outcomes. The PI3K/AKT/mTOR pathway is a key focus in BC therapy because it plays a major role in important processes like tumor growth, survival, and resistance to treatment. Targeting this pathway could lead to better treatment options and outcomes. The present review explores how the PI3K/AKT/mTOR pathway becomes dysregulated in BC, focusing on the genetic changes like PIK3CA mutations and PTEN loss that leads to its aggravation. Current treatment options include the use of inhibitors targeting PI3K, AKT, and mTOR with combination therapies showing promise in overcoming drug resistance and improving effectiveness. Looking ahead, next-generation inhibitors and personalized treatment plans guided by biomarker analysis may provide more accurate and effective options for patients. Integrating these pathway inhibitors with immunotherapy offers an exciting opportunity to boost anti-tumor responses and improve survival rates. This review offers a comprehensive summary of the current progress in targeting the PI3K/AKT/mTOR pathway in BC. It highlights future research directions and therapeutic strategies aimed at enhancing patient outcomes and quality of life.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116850"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571933","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting the CXCR7 pathway with TC14012 to inhibit endothelial necroptosis and lung cancer metastasis TC14012靶向CXCR7通路抑制内皮坏死下垂和肺癌转移

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-04 DOI: 10.1016/j.bcp.2025.116852

Huifeng Hao , Wenjia Tian , Jingjing Gong , Junfeng Li , Shiyan Zhou , Zhengwang Guo , Yanna Jiao , Dong Xue , Shuyan Han , Pingping Li

{"title":"Targeting the CXCR7 pathway with TC14012 to inhibit endothelial necroptosis and lung cancer metastasis","authors":"Huifeng Hao , Wenjia Tian , Jingjing Gong , Junfeng Li , Shiyan Zhou , Zhengwang Guo , Yanna Jiao , Dong Xue , Shuyan Han , Pingping Li","doi":"10.1016/j.bcp.2025.116852","DOIUrl":"10.1016/j.bcp.2025.116852","url":null,"abstract":"<div><div>Endothelial necroptosis plays a crucial role in regulating cancer metastasis. Our previous research demonstrated that TC14012, which is an agonist of CXCR7, exhibits protective effects against endothelial injury. This study was designed to elucidate the effects of TC14012 on endothelial necroptosis and cancer lung metastasis, along with deciphering the underlying molecular mechanisms. The <em>trans</em>-well analysis system was used to evaluate the <em>trans</em>-endothelial migration ability of the tumor cells. Cell death was evaluated with Ethidium Homodimer 3 (EthD-3) staining and flow cytometry analysis. The expression and phosphorylation of MLKL or RIPK3 were evaluated using Western blot. The effects of TC14012 on cancer lung metastasis <em>in vivo</em> were determined using the mouse hematogenous metastasis model. The results showed that TC14012 treatment significantly suppressed <em>trans</em>-endothelial migration of lung cancer cells, through effectively counteracting endothelial cell death induced by the tumor cells <em>in vitro</em>. Upon inhibition of cell necroptosis with necrosulfonamide (NSA), an MLKL inhibitor, the suppressive effects of TC14012 on endothelial cell death were significantly alleviated. Further investigations unveiled that TC14012, via its interaction with CXCR7 receptor rather than CXCR4, impeded the phosphorylation and subsequent activation of the RIPK3/MLKL signaling cascade. Ultimately, <em>in vivo</em> experiments demonstrated that administration of TC14012 mitigated lung infiltration of pre-labeled tumor cells and reduced lung metastasis in mice subsequent to intravenous injection of tumor cells. In summary, TC14012 effectively retards lung cancer metastasis by inhibiting endothelial necroptosis and the consequential <em>trans</em>-endothelial migration of tumor cells, through modulating the CXCR7/RIPK3/MLKL signaling.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116852"},"PeriodicalIF":5.3,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143571934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging roles of EGFL family members in neoplastic diseases: Molecular mechanisms and targeted therapies EGFL家族成员在肿瘤疾病中的新作用：分子机制和靶向治疗

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-03 DOI: 10.1016/j.bcp.2025.116847

Xiaoge Gao , Guopeng zhang , Feitong Wang , Wenhui Ruan , Shishuo Sun , Qing Zhang , Xiangye Liu

{"title":"Emerging roles of EGFL family members in neoplastic diseases: Molecular mechanisms and targeted therapies","authors":"Xiaoge Gao , Guopeng zhang , Feitong Wang , Wenhui Ruan , Shishuo Sun , Qing Zhang , Xiangye Liu","doi":"10.1016/j.bcp.2025.116847","DOIUrl":"10.1016/j.bcp.2025.116847","url":null,"abstract":"<div><div>Epidermal growth factor-like proteins (EGFLs) contain more than a single EGF/EGF-like domain within their protein structure. To date, ten EGFL family members (EGFL1-10) have been characterized across diverse tissues and developmental stages under different conditions. In this review, we conclude that EGFLs are instrumental in regulating biological activities and pathological processes. Under physiological conditions, EGFLs participate in angiogenesis, neurogenesis, osteogenesis, and other processes. Under pathological conditions, EGFLs are linked with different diseases, particularly cancers. Furthermore, we highlight recent advancements in the study of EGFLs in biological conditions and cancers. In addition, the regulatory role and key underlying mechanism of EGFLs in mediating tumorigenesis are discussed. This paper also examines potential antagonists that target EGFL family members in cancer therapeutics. In summary, this comprehensive review elucidates the critical role of EGFLs in neoplastic diseases and highlights their potential as therapeutic targets.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"236 ","pages":"Article 116847"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143547932","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Targeting fibroblast growth factor receptor (FGFR) with inhibitors in head and neck cancers: Their roles, mechanisms and challenges 靶向成纤维细胞生长因子受体（FGFR）抑制剂在头颈癌中的作用、机制和挑战

IF 5.3 2区医学

Biochemical pharmacology Pub Date : 2025-03-03 DOI: 10.1016/j.bcp.2025.116845

Daowen Luo , Sirinart Kumfu , Nipon Chattipakorn , Siriporn C. Chattipakorn

{"title":"Targeting fibroblast growth factor receptor (FGFR) with inhibitors in head and neck cancers: Their roles, mechanisms and challenges","authors":"Daowen Luo , Sirinart Kumfu , Nipon Chattipakorn , Siriporn C. Chattipakorn","doi":"10.1016/j.bcp.2025.116845","DOIUrl":"10.1016/j.bcp.2025.116845","url":null,"abstract":"<div><div>Head and neck squamous cell carcinoma (HNSCC) is a common and aggressive type of cancer with significant rates of morbidity and mortality. Traditional treatment options, including radiotherapy, chemotherapy, and surgery, are widely used, but their effectiveness can be uncertain. As research in cancer therapies evolves, molecular-targeted therapies are increasingly recognized as promising alternatives for managing malignant tumors. Fibroblast growth factor receptors (FGFRs) have been shown to be one of the essential components in the pathways in the progression of HNSCC. This review aims to summarize and discuss the structure, functions, signaling pathways, abnormal alterations of FGFRs, and their roles in tumorigenesis and development. We have accumulated information from <em>in vitro, in vivo,</em> and clinical studies regarding FGFR inhibitors in HNSCC. However, the efficacy of FGFR inhibitors as a cancer therapy is limited, which may be due to the resistance to FGFR inhibitors. In this review we also discuss the potential mechanisms of FGFR inhibitor resistance in HNSCC. By enriching our understanding of the treatment with and resistance of FGFR inhibitors in HNSCC, researchers may unveil new therapeutic targets or strategies to enhance the efficacy of FGFR inhibitors in this context.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"235 ","pages":"Article 116845"},"PeriodicalIF":5.3,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143549620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0