Ruoxue Chen, Xuan Huang, Jiayun Hou, Junjie Ni, Wenrui Zhao, Quanlin Li, Heng Jiao, Xin Cao
{"title":"ZSH-2208：一种新型类维生素A通过RARγ-TNFAIP3轴对ESCC干细胞具有有效的抗肿瘤作用。","authors":"Ruoxue Chen, Xuan Huang, Jiayun Hou, Junjie Ni, Wenrui Zhao, Quanlin Li, Heng Jiao, Xin Cao","doi":"10.1002/ctm2.70148","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Backgroud</h3>\n \n <p>Oesophageal cancer ranks among the most prevalent malignant tumours globally, primarily consisting of oesophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSCs) accelerate the progression ESCC via their strong self-renewal and tumourigenic capabilities, presenting significant clinical challenges due to increased risks of recurrence and drug resistance.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>Our previous study has reported WYC-209, which is capable of inducing apoptosis of CSCs in melanoma and hepatoma, but is ineffective against ESCC. Additionally, clinical studies in ESCC still lack drug candidates that effectively target CSCs. Therefore, our team developed a series of novel retinoids that target retinoic acid receptors (RARs), with enhanced potency, broader efficacy and minimised toxic side effects against CSCs. Following iterative optimisation and pharmacological validation, ZSH-2208 was identified as the most promising candidate for effectively targeting ESCC tumour-repopulating cells (TRCs). Mechanistic exploration revealed that ZSH-2208 inhibits the growth of ESCC-TRCs through modulation of the RARγ–TNFAIP3 axis. The clinical significance of the key molecule TNFAIP3 in ESCC has also been demonstrated.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>This study introduces ZSH-2208, a novel retinoid specifically targeting ESCC-TRCs, which holds significant potential for clinical application in ESCC.</p>\n </section>\n \n <section>\n \n <h3> Key points</h3>\n \n <div>\n <ul>\n \n <li>\n <p>The ESCC-TRCs replicates the characteristics of ESCC stem cells, which are inhibited by ZSH-2208.</p>\n </li>\n \n <li>In vivo and in vitro experiments demonstrated that ZSH-2208, a novel RA analogue, effectively inhibits the growth of ESCC-TRCs through the RARγ–TNFAIP3 axis.</li>\n \n <li>\n <p>Low levels of TNFIP3 protein may be associated with improved survival probability in ESCC patients.</p>\n </li>\n </ul>\n </div>\n </section>\n </div>","PeriodicalId":10189,"journal":{"name":"Clinical and Translational Medicine","volume":"15 1","pages":""},"PeriodicalIF":7.9000,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670471/pdf/","citationCount":"0","resultStr":"{\"title\":\"ZSH-2208: A novel retinoid with potent anti-tumour effects on ESCC stem cells via RARγ–TNFAIP3 axis\",\"authors\":\"Ruoxue Chen, Xuan Huang, Jiayun Hou, Junjie Ni, Wenrui Zhao, Quanlin Li, Heng Jiao, Xin Cao\",\"doi\":\"10.1002/ctm2.70148\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Backgroud</h3>\\n \\n <p>Oesophageal cancer ranks among the most prevalent malignant tumours globally, primarily consisting of oesophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSCs) accelerate the progression ESCC via their strong self-renewal and tumourigenic capabilities, presenting significant clinical challenges due to increased risks of recurrence and drug resistance.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>Our previous study has reported WYC-209, which is capable of inducing apoptosis of CSCs in melanoma and hepatoma, but is ineffective against ESCC. Additionally, clinical studies in ESCC still lack drug candidates that effectively target CSCs. Therefore, our team developed a series of novel retinoids that target retinoic acid receptors (RARs), with enhanced potency, broader efficacy and minimised toxic side effects against CSCs. Following iterative optimisation and pharmacological validation, ZSH-2208 was identified as the most promising candidate for effectively targeting ESCC tumour-repopulating cells (TRCs). Mechanistic exploration revealed that ZSH-2208 inhibits the growth of ESCC-TRCs through modulation of the RARγ–TNFAIP3 axis. The clinical significance of the key molecule TNFAIP3 in ESCC has also been demonstrated.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>This study introduces ZSH-2208, a novel retinoid specifically targeting ESCC-TRCs, which holds significant potential for clinical application in ESCC.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Key points</h3>\\n \\n <div>\\n <ul>\\n \\n <li>\\n <p>The ESCC-TRCs replicates the characteristics of ESCC stem cells, which are inhibited by ZSH-2208.</p>\\n </li>\\n \\n <li>In vivo and in vitro experiments demonstrated that ZSH-2208, a novel RA analogue, effectively inhibits the growth of ESCC-TRCs through the RARγ–TNFAIP3 axis.</li>\\n \\n <li>\\n <p>Low levels of TNFIP3 protein may be associated with improved survival probability in ESCC patients.</p>\\n </li>\\n </ul>\\n </div>\\n </section>\\n </div>\",\"PeriodicalId\":10189,\"journal\":{\"name\":\"Clinical and Translational Medicine\",\"volume\":\"15 1\",\"pages\":\"\"},\"PeriodicalIF\":7.9000,\"publicationDate\":\"2024-12-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11670471/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Clinical and Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70148\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Clinical and Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ctm2.70148","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
ZSH-2208: A novel retinoid with potent anti-tumour effects on ESCC stem cells via RARγ–TNFAIP3 axis
Backgroud
Oesophageal cancer ranks among the most prevalent malignant tumours globally, primarily consisting of oesophageal squamous cell carcinoma (ESCC). Cancer stem cells (CSCs) accelerate the progression ESCC via their strong self-renewal and tumourigenic capabilities, presenting significant clinical challenges due to increased risks of recurrence and drug resistance.
Methods
Our previous study has reported WYC-209, which is capable of inducing apoptosis of CSCs in melanoma and hepatoma, but is ineffective against ESCC. Additionally, clinical studies in ESCC still lack drug candidates that effectively target CSCs. Therefore, our team developed a series of novel retinoids that target retinoic acid receptors (RARs), with enhanced potency, broader efficacy and minimised toxic side effects against CSCs. Following iterative optimisation and pharmacological validation, ZSH-2208 was identified as the most promising candidate for effectively targeting ESCC tumour-repopulating cells (TRCs). Mechanistic exploration revealed that ZSH-2208 inhibits the growth of ESCC-TRCs through modulation of the RARγ–TNFAIP3 axis. The clinical significance of the key molecule TNFAIP3 in ESCC has also been demonstrated.
Results
This study introduces ZSH-2208, a novel retinoid specifically targeting ESCC-TRCs, which holds significant potential for clinical application in ESCC.
Key points
The ESCC-TRCs replicates the characteristics of ESCC stem cells, which are inhibited by ZSH-2208.
In vivo and in vitro experiments demonstrated that ZSH-2208, a novel RA analogue, effectively inhibits the growth of ESCC-TRCs through the RARγ–TNFAIP3 axis.
Low levels of TNFIP3 protein may be associated with improved survival probability in ESCC patients.
期刊介绍：
Clinical and Translational Medicine (CTM) is an international, peer-reviewed, open-access journal dedicated to accelerating the translation of preclinical research into clinical applications and fostering communication between basic and clinical scientists. It highlights the clinical potential and application of various fields including biotechnologies, biomaterials, bioengineering, biomarkers, molecular medicine, omics science, bioinformatics, immunology, molecular imaging, drug discovery, regulation, and health policy. With a focus on the bench-to-bedside approach, CTM prioritizes studies and clinical observations that generate hypotheses relevant to patients and diseases, guiding investigations in cellular and molecular medicine. The journal encourages submissions from clinicians, researchers, policymakers, and industry professionals.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
