Mashima Tetsuo
Division of Molecular Biotherapy, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research.
Yakugaku Zasshi. 2017;137(2):129-132. doi: 10.1248/yakushi.16-00229-1.
The emergence of drug resistance is a major obstacle to the successful pharmacological treatment of cancer. Tumor heterogeneity is one of the key factors underlying drug resistance. Cancer cell heterogeneity in tumors is caused by genetic mutation and by the existence of cancer stem cells (CSCs). CSCs are defined as a subpopulation of highly tumorigenic cancer cells with self-renewal activity. It has been reported that various types of cancer involve CSCs, and that CSCs are generally resistant to anticancer drugs. Therefore, CSC-targeting agents could allow for more effective pharmacological treatment of cancer. Using a comprehensive gene expression study and functional genomic approach, we are trying to identify CSC-specific survival factors, as well as candidate compounds that interfere with CSC-selective survival signaling. These CSC-targeting drugs could be promising new therapeutic agents which would suppress the emergence of drug-resistant cells and enhance the effect of antitumor agents.
耐药性的出现是癌症药物治疗成功的主要障碍。肿瘤异质性是耐药性的关键因素之一。肿瘤中的癌细胞异质性是由基因突变和癌症干细胞(CSCs)的存在引起的。癌症干细胞被定义为具有自我更新活性的高致瘤性癌细胞亚群。据报道,各种类型的癌症都涉及癌症干细胞,并且癌症干细胞通常对抗癌药物具有抗性。因此,靶向癌症干细胞的药物可以实现更有效的癌症药物治疗。通过全面的基因表达研究和功能基因组学方法,我们试图识别癌症干细胞特异性存活因子以及干扰癌症干细胞选择性存活信号的候选化合物。这些靶向癌症干细胞的药物可能是有前景的新型治疗药物,它们将抑制耐药细胞的出现并增强抗肿瘤药物的效果。