Ishii Hideshi, Iwatsuki Masaaki, Ieta Keisuke, Ohta Daisuke, Haraguchi Naotsugu, Mimori Koshi, Mori Masaki
Department of Gastroenterological Surgery, Osaka University, Graduate School of Medicine, Suita, Osaka, Japan.
Cancer Sci. 2008 Oct;99(10):1871-7. doi: 10.1111/j.1349-7006.2008.00914.x.
Cancer is a disease of genetic and epigenetic alterations, which are emphasized as the central mechanisms of tumor progression in the multistepwise model. Discovery of rare subpopulations of cancer stem cells (CSCs) has created a new focus in cancer research. The heterogeneity of tumors can be explained with the help of CSCs supported by antiapoptotic signaling. CSCs mimic normal adult stem cells by demonstrating resistance to toxic injuries and chemoradiation therapy. Moreover, they might be responsible for tumor relapse following apparent beneficial treatments. Compared with hematopoietic malignancies, conventional therapy regimes in solid tumors have improved the overall survival marginally, illustrating the profound impact of treatment resistance. This implies that the present therapies, which follow total elimination of rapidly dividing and differentiated tumor cells, need to be modified to target CSCs that repopulate the tumor. In this review article, we report on recent findings regarding the involvement of CSCs in chemoradiation resistance and provide new insights into their therapeutic implications in cancer.
癌症是一种发生基因和表观遗传改变的疾病,在多步骤模型中,这些改变被视为肿瘤进展的核心机制。癌症干细胞(CSCs)罕见亚群的发现为癌症研究带来了新的焦点。肿瘤的异质性可借助抗凋亡信号支持的癌症干细胞来解释。癌症干细胞通过表现出对毒性损伤和放化疗的抗性,来模拟正常成体干细胞。此外,它们可能是明显有效的治疗后肿瘤复发的原因。与血液系统恶性肿瘤相比,实体瘤的传统治疗方案仅略微提高了总生存率,这说明了治疗抗性的深远影响。这意味着,目前旨在完全消除快速分裂和分化的肿瘤细胞的疗法,需要加以改进,以靶向那些使肿瘤重新增殖的癌症干细胞。在这篇综述文章中,我们报告了关于癌症干细胞参与放化疗抗性的最新发现,并对其在癌症治疗中的意义提供了新的见解。