Bukowska Barbara, Rogalska Aneta, Marczak Agnieszka
Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Str, 90-236 Lodz, Poland.
Department of Medical Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143 Str, 90-236 Lodz, Poland.
Life Sci. 2016 Apr 15;151:86-92. doi: 10.1016/j.lfs.2016.02.095. Epub 2016 Mar 2.
Despite more modern therapeutics approaches and the use of new drugs for chemotherapy, patients with ovarian cancer still have poor prognosis and therefore, new strategies for its cure are highly needed. One of the promising ways is combined therapy, which has many advantages as minimizing drug resistance, enhancing efficacy of treatment, and reducing toxicity. Combined therapy has rich and successful history in the field of ovarian cancer treatment. Currently use therapy is usually based on platinum-containing agent (carboplatin or cisplatin) and a member of taxanes (paclitaxel or docetaxel). In the mid-2000s this standard regimen has been expanded with bevacizumab, monoclonal antibody directed to Vascular Endothelial Growth Factor (VEGF). Another drug combination with promising perspectives is WP 631 given together with epothilone B (Epo B). WP 631 is a bisanthracycline composed of two molecules of daunorubicin linked with a p-xylenyl linker. Epo B is a 16-membered macrolide manifesting similar mechanism of action to taxanes. Their effectiveness against ovarian cancer as single agents is well established. However, the combination of WP 631 and Epo B appeared to act synergistically, meaning that it is much more potent than the single drugs. The mechanism lying under its efficacy includes disturbing essential cell cycle-regulating proteins leading to mitotic slippage and following apoptosis, as well as affecting EpCAM and HMGB1 expression. In this article, we summarized the current state of knowledge regarding combined therapy based on WP 631 and Epo B as a potential way of ovarian cancer treatment.
尽管有了更现代的治疗方法以及使用新药进行化疗,但卵巢癌患者的预后仍然很差,因此,迫切需要新的治愈策略。一种有前景的方法是联合治疗,它具有许多优点,如将耐药性降至最低、提高治疗效果以及降低毒性。联合治疗在卵巢癌治疗领域有着丰富且成功的历史。目前常用的治疗方法通常基于含铂药物(卡铂或顺铂)和紫杉烷类药物(紫杉醇或多西他赛)中的一种。在21世纪中叶,这种标准方案因加入贝伐单抗(一种针对血管内皮生长因子(VEGF)的单克隆抗体)而得到扩展。另一种前景广阔的药物组合是WP 631与埃坡霉素B(Epo B)联合使用。WP 631是一种双蒽环类药物,由两个柔红霉素分子通过对二甲苯基连接子连接而成。Epo B是一种16元大环内酯类药物,其作用机制与紫杉烷类药物相似。它们作为单一药物对卵巢癌的有效性已得到充分证实。然而,WP 631和Epo B的组合似乎具有协同作用,这意味着它比单一药物的效力要强得多。其疗效背后的机制包括干扰关键的细胞周期调节蛋白,导致有丝分裂滑脱并随后引发凋亡,以及影响上皮细胞黏附分子(EpCAM)和高迁移率族蛋白B1(HMGB1)的表达。在本文中,我们总结了关于基于WP 631和Epo B的联合治疗作为卵巢癌潜在治疗方法的当前知识状态。