National Cancer Institute, Division of Cancer Treatment and Diagnosis, Cancer Therapy Evaluation Program, Investigational Drug Branch, EPN7131, 6130 Executive Boulevard, Rockville, Bethesda, MD 20852, USA.
Nat Rev Clin Oncol. 2011 Feb;8(2):97-106. doi: 10.1038/nrclinonc.2010.196. Epub 2010 Dec 14.
Tumor relapse and metastasis remain major obstacles for improving overall cancer survival, which may be due at least in part to the existence of cancer stem cells (CSCs). CSCs are characterized by tumorigenic properties and the ability to self-renew, form differentiated progeny, and develop resistance to therapy. CSCs use many of the same signaling pathways that are found in normal stem cells, such as Wnt, Notch, and Hedgehog (Hh). The origin of CSCs is not fully understood, but data suggest that they originate from normal stem or progenitor cells, or possibly other cancer cells. Therapeutic targeting of both CSCs and bulk tumor populations may provide a strategy to suppress tumor regrowth. Development of agents that target critical steps in the Wnt, Notch, and Hh pathways will be complicated by signaling cross-talk. The role that embryonic signaling pathways play in the function of CSCs, the development of new anti-CSC therapeutic agents, and the complexity of potential CSC signaling cross-talk are described in this Review.
肿瘤复发和转移仍然是提高癌症总体生存率的主要障碍，这可能至少部分归因于癌症干细胞 (CSC) 的存在。CSC 的特征是具有致瘤特性和自我更新能力，能够形成分化后代，并对治疗产生耐药性。CSC 使用与正常干细胞相同的信号通路，例如 Wnt、Notch 和 Hedgehog (Hh)。CSC 的起源尚不完全清楚，但数据表明它们起源于正常干细胞或祖细胞，或者可能来自其他癌细胞。针对 CSC 和肿瘤群体的治疗靶向可能提供抑制肿瘤再生的策略。开发针对 Wnt、Notch 和 Hh 途径关键步骤的药物将因信号转导交叉对话而变得复杂。本综述描述了胚胎信号通路在 CSC 功能中的作用、新的抗 CSC 治疗药物的开发以及潜在 CSC 信号转导交叉对话的复杂性。
