Since their discovery from natural sources, the potent cytotoxic effects of combretastatins were widely studied for the application in antitumor therapy. However, major pharmacokinetic issues as low water solubility and chemical instability of the double bond configuration prevented their use in therapy. A lot of efforts have been directed towards the search of novel strategies, allowing a safer use of combretastatins as anticancer agents. This review analyses the recent landscape in combretastatin research, characterized by the identification of hybrids, prodrugs, and novel combination treatments. Interestingly, the potent cytotoxic agent combretastatin A4 (CA4) was recently proposed as payload in the construction of novel antibody-drug conjugates (ADCs), allowing an efficient targeting of the cytotoxic agent to specific tumors.

中文翻译：

---

抗肿瘤 combretastatins 的新生活：杂交种、前药、联合疗法和抗体-药物偶联物的最新发展


自从他们从天然来源发现以来，combretastatins 的强大细胞毒作用被广泛研究用于抗肿瘤治疗。然而，水溶性低和双键构型的化学不稳定性等主要药代动力学问题阻止了它们在治疗中的应用。已经投入了大量精力来寻找新的策略，允许更安全地使用 combretastatins 作为抗癌剂。本综述分析了 combretastatin 研究的最新情况，其特征是鉴定杂交种、前药和新型联合治疗。有趣的是，最近提议将强效细胞毒性药物 combretastatin A4 （CA4） 作为构建新型抗体-药物偶联物 （ADC） 的有效载荷，从而允许细胞毒性药物有效靶向特定肿瘤。