Lewis Alexander C, Wallington-Beddoe Craig T, Powell Jason A, Pitson Stuart M
Centre for Cancer Biology, University of South Australia and SA Pathology, UniSA CRI Building, North Terrace, Adelaide, SA, 5001, Australia.
Adelaide Medical School, University of Adelaide, Adelaide, SA, 5000, Australia.
Cell Death Discov. 2018 Jun 28;4:72. doi: 10.1038/s41420-018-0075-0. eCollection 2018.
Conventional chemotherapy-based drug combinations have, until recently, been the backbone of most therapeutic strategies for cancer. In a time of emerging rationale drug development, targeted therapies are beginning to be added to traditional chemotherapeutics to synergistically enhance clinical responses. Of note, the importance of pro-apoptotic ceramide in mediating the anti-cancer effects of these therapies is becoming more apparent. Furthermore, reduced cellular ceramide in favour of pro-survival sphingolipids correlates with tumorigenesis and most importantly, drug resistance. Thus, agents that manipulate sphingolipid metabolism have been explored as potential anti-cancer agents and have recently demonstrated exciting potential to augment the efficacy of anti-cancer therapeutics. This review examines the biology underpinning these observations and the potential use of sphingolipid manipulating agents in the context of existing and emerging therapies for haematological malignancies.
直到最近，基于传统化疗的药物组合一直是大多数癌症治疗策略的核心。在合理药物开发不断涌现的时代，靶向治疗开始被添加到传统化疗药物中，以协同增强临床反应。值得注意的是，促凋亡神经酰胺在介导这些疗法的抗癌作用中的重要性正变得越来越明显。此外，细胞内神经酰胺减少而有利于促生存鞘脂与肿瘤发生相关，最重要的是与耐药性相关。因此，调节鞘脂代谢的药物已被探索作为潜在的抗癌药物，并且最近已显示出增强抗癌治疗疗效的令人兴奋的潜力。这篇综述探讨了这些观察结果背后的生物学原理，以及鞘脂调节药物在现有和新兴血液系统恶性肿瘤治疗中的潜在用途。
