Thoracic Oncology Research Group, School of Clinical Medicine, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College, Dublin, Ireland.
Flow Cytometry Facility, Trinity Translational Medicine Institute, Trinity Centre for Health Sciences, St. James's Hospital and Trinity College, Dublin, Ireland.
Cancer Lett. 2018 Aug 1;428:117-126. doi: 10.1016/j.canlet.2018.04.008. Epub 2018 Apr 11.
Non-small cell lung cancer (NSCLC) is the most common cause of cancer-related deaths worldwide. While partial or complete tumor regression can be achieved in patients, particularly with cisplatin-based strategies, these initial responses are frequently short-lived and are followed by tumor relapse and chemoresistance. Identifying the root of cisplatin resistance in NSCLC and elucidating the mechanism(s) of tumor relapse, is of critical importance in order to determine the point of therapeutic failure, which in turn, will aid the discovery of novel therapeutics, new combination strategies and a strategy to enhance the efficacy of current chemotherapeutics. It has been hypothesized that cancer stem cells (CSCs) may be the initiating factor of resistance. We have previously identified and characterized an aldehyde dehydrogenase 1 CSC subpopulation in cisplatin resistant NSCLC. BBI608 is a small molecule STAT3 inhibitor known to suppress cancer relapse, progression and metastasis. Here, we show that BBI608 can inhibit stemness gene expression, deplete CSCs and overcome cisplatin resistance in NSCLC.
非小细胞肺癌（NSCLC）是全球癌症相关死亡的最常见原因。虽然患者，特别是使用顺铂为基础的策略的患者，可以实现部分或完全肿瘤消退，但这些初始反应往往是短暂的，随后是肿瘤复发和化疗耐药。确定 NSCLC 中顺铂耐药的根源，并阐明肿瘤复发的机制，对于确定治疗失败的关键点至关重要，这反过来又将有助于发现新的治疗方法、新的联合策略和增强现有化疗药物疗效的策略。有人假设癌症干细胞（CSC）可能是耐药的起始因素。我们之前已经在顺铂耐药的 NSCLC 中鉴定并表征了一种醛脱氢酶 1 CSC 亚群。BBI608 是一种已知可以抑制癌症复发、进展和转移的小分子 STAT3 抑制剂。在这里，我们表明 BBI608 可以抑制干性基因表达，耗竭 CSC 并克服 NSCLC 中的顺铂耐药性。
