Ali Muhammad Asif, Khan Azmat Ullah, Ali Ahmad, Khaliq Muniba, Khan Noohela, Mujahid Sania, Calina Daniela, Püsküllüoğlu Mirosława, Sharifi-Rad Javad
Department of Food Science and Human Nutrition, University of Veterinary & Animal Sciences, Lahore, Pakistan.
Faculty of Rehabilitation and Allied Health Sciences (FRAHS), Riphah International University, Gulberg III, Lahore, Pakistan.
Med Oncol. 2025 Jan 11;42(2):43. doi: 10.1007/s12032-024-02594-0.
Didemnins, a class of cyclic depsipeptides derived from marine organisms exhibit notable anticancer properties. Among them, Didemnin B has been extensively researched for its strong antitumor activity and progression to clinical trials. Nonetheless, its clinical application has been impeded by challenges like poor bioavailability and dose-limiting toxicity. This review aims to provide a comprehensive analysis of the anticancer mechanisms of Didemnins, particularly Didemnin B, by examining studies that investigate their anticancer properties, mechanisms of action, pharmacokinetics, and clinical outcomes, while exploring their potential as therapeutic agents in cancer treatment. A comprehensive review of the literature was conducted using scientific databases, including PubMed, Google Scholar and ScienceDirect. Didemnin B has been shown to exert its anticancer effects primarily through the inhibition of protein synthesis, induction of apoptosis, and disruption of cell-cycle progression. Despite promising preclinical results, clinical trials have revealed substantial toxicity, particularly neuromuscular and hepatic, which significantly constrains its therapeutic potential. Recent progress in developing semisynthetic derivatives, including Dehydrodidemnin B (Plitidepsin, Aplidin), have led to improved efficacy and reduced toxicity. Didemnins, especially Didemnin B, hold promise as anticancer agents. However, future research should focus on optimizing delivery methods, reducing toxicity, and exploring combination therapies to enhance their therapeutic potential in oncology.
地棘蛙素是一类源自海洋生物的环缩肽，具有显著的抗癌特性。其中，地棘蛙素B因其强大的抗肿瘤活性以及进入临床试验阶段而受到广泛研究。尽管如此，其临床应用受到生物利用度低和剂量限制性毒性等挑战的阻碍。本综述旨在通过审视研究地棘蛙素，特别是地棘蛙素B的抗癌特性、作用机制、药代动力学和临床结果的研究，同时探索它们在癌症治疗中作为治疗药物的潜力，从而对地棘蛙素的抗癌机制进行全面分析。使用包括PubMed、谷歌学术和ScienceDirect在内的科学数据库对文献进行了全面综述。已表明地棘蛙素B主要通过抑制蛋白质合成、诱导细胞凋亡和破坏细胞周期进程发挥其抗癌作用。尽管临床前结果很有前景，但临床试验显示出显著的毒性，尤其是神经肌肉毒性和肝脏毒性极大地限制了其治疗潜力。开发半合成衍生物（包括脱氢地棘蛙素B（普利地辛，阿普利定））的最新进展已带来疗效的改善和毒性的降低。地棘蛙素，尤其是地棘蛙素B，有望成为抗癌药物。然而，未来的研究应集中在优化给药方法、降低毒性以及探索联合疗法，以提高它们在肿瘤学中的治疗潜力。
