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Sorafenib generates microvesicle particles in non-small cell lung cancer. 索拉非尼在非小细胞肺癌中产生微泡颗粒。

Tumor discovery Pub Date : 2025-09-23 Epub Date: 2025-06-19 DOI: 10.36922/td025110019

Yevgeniy Gladkiy, Anita Thyagarajan, Morgann Hendrixson, Ravi P Sahu

{"title":"Sorafenib generates microvesicle particles in non-small cell lung cancer.","authors":"Yevgeniy Gladkiy, Anita Thyagarajan, Morgann Hendrixson, Ravi P Sahu","doi":"10.36922/td025110019","DOIUrl":"10.36922/td025110019","url":null,"abstract":"Despite the improved clinical outcomes resulting from the use of sorafenib, the development of resistance mechanisms continues to undermine its treatment efficacy. Recent studies have implicated the role of a phospholipid mediator, platelet-activating factor receptor (PAFR) pathway, and extracellular vesicles known as microvesicle particles (MVP) in influencing cellular behavior and the efficacy of therapeutic agents. In this study, we determined the impact of the PAFR pathway and the acid sphingomyelinase (aSMase), which is required for the biogenesis of MVP, on sorafenib-induced effects on lung cancer growth and MVP release. Using A549 and H1299 non-small cell lung cancer (NSCLC) cell lines, we showed that sorafenib treatment reduced cell viability in a dose and time-dependent manner. Notably, sorafenib also enhanced MVP formation in both NSCLC cell lines. This MVP release was significantly attenuated by pharmacologic inhibition of the PAFR pathway through the WEB2086 compound and the aSMase inhibitor, imipramine, indicating the involvement of the PAFR and aSMase in sorafenib-induced MVP biogenesis. Moreover, co-treatment with imipramine enhanced the cytotoxic effects of sorafenib, suggesting that targeting MVP-associated pathways may improve sorafenib response. Collectively, these findings offer mechanistic insight into how sorafenib modulates MVP release and supports the therapeutic potential of combining tyrosine kinase inhibitors with agents that disrupt MVP biogenesis in NSCLC.","PeriodicalId":521075,"journal":{"name":"Tumor discovery","volume":"4 3","pages":"81-91"},"PeriodicalIF":0.0,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12525023/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145310554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Honokiol in cancer: Roles in enhancing combination therapy efficacy and preventing post-transplant malignancies. 本木酚在癌症中的作用：提高联合治疗疗效和预防移植后恶性肿瘤。

Tumor discovery Pub Date : 2025-01-01 Epub Date: 2025-05-05 DOI: 10.36922/td.8152

Laxminarayan Rawat, Raghu Solanki, Rahul Kumar, Soumitro Pal, Akash Sabarwal

{"title":"Honokiol in cancer: Roles in enhancing combination therapy efficacy and preventing post-transplant malignancies.","authors":"Laxminarayan Rawat, Raghu Solanki, Rahul Kumar, Soumitro Pal, Akash Sabarwal","doi":"10.36922/td.8152","DOIUrl":"10.36922/td.8152","url":null,"abstract":"Therapeutic resistance remains a significant challenge in cancer treatment, often resulting in relapse and poor outcomes. Conventional chemotherapies, such as cisplatin and paclitaxel, are frequently undermined by the development of chemoresistance and systemic toxicity. Targeted therapies, such as receptor tyrosine kinase (RTKs) inhibitors and monoclonal antibodies (mAbs), offer better specificity but face resistance over time. Combination therapies are being explored to improve efficacy and mitigate resistance. Honokiol, a biphenolic natural compound derived from Magnolia species, has emerged as a potential adjunct in combination therapies due to its anti-cancer, anti-inflammatory, and immunomodulatory properties. It enhances the efficacy of chemotherapies, such as cisplatin and paclitaxel, RTK inhibitors, such as cabozantinib and erlotinib, and mAbs, such as cetuximab. Notably, honokiol combined with mAbs has shown promise in pre-clinical studies by reactivating the immune system and reducing tumor growth in resistant models. In addition, honokiol aids in post-transplant cancer prevention by modulating immune responses, reducing tumor progression, and lowering the required dose of immunosuppressants, such as cyclosporine A and rapamycin. Pre-clinical studies in renal cell carcinoma (RCC), head and neck squamous cell carcinoma (HNSCC), and non-small cell lung cancer emphasize its potential to overcome resistance. Despite promising evidence, further clinical studies are needed to validate honokiol as a viable adjunct in combination therapies. While several reviews have focused on the effects of honokiol alone, there is a lack of comprehensive studies examining its potential in combination with other therapies. This review aims to fill this gap by offering critical insights into the role of honokiol as a candidate for combination therapy.","PeriodicalId":521075,"journal":{"name":"Tumor discovery","volume":"4 2","pages":"42-54"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12463189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145188288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0