Department of Cancer Biology, Wake Forest University School of Medicine, 1 Medical Center Blvd., Winston-Salem, NC 27157, USA.
Stem Cell Rev Rep. 2011 Jun;7(2):307-14. doi: 10.1007/s12015-010-9205-7.
While cancer treatment modalities are gradually improving due to increased knowledge about tumor heterogeneity and the cancer stem cell hypothesis, there remains a disconnect between tumor detection and mortality rates. The increasing knowledge of stem cell biology and its contribution to cancer progression illuminates the potential for chemopreventative regimens that effectively target the tissue-specific stem cell. Several signaling pathways have emerged that are critical for regulating stem cell self-renewal and multilineage differentiation over a range of tissue types, including Wnt, Hedgehog, and Notch signaling. Dysregulation of these genes can lead to cancer, which supports the cancer stem cell hypothesis. Several known chemopreventative agents have recently been shown to impact these and other pathways in the stem cell population, suggesting that their efficacies may be attributed in part to maintaining homeostasis of tissue-specific stem cells. Further understanding of the mechanisms of action of chemopreventative agents and of stem cell biology will generate better chemoprevention regimens that can be recommended especially to those in high-risk populations.
尽管由于对肿瘤异质性和癌症干细胞假说的认识不断提高，癌症治疗方法逐渐得到改善，但肿瘤检测和死亡率之间仍然存在脱节。对干细胞生物学的认识不断提高，以及它对癌症进展的贡献，为开发能够有效针对特定组织干细胞的化学预防方案提供了潜力。已经出现了几种信号通路，这些信号通路对于调节干细胞的自我更新和多谱系分化至关重要，包括 Wnt、Hedgehog 和 Notch 信号通路。这些基因的失调可导致癌症，这支持癌症干细胞假说。最近已经证明，几种已知的化学预防剂可影响干细胞群体中的这些和其他通路，这表明它们的疗效部分归因于维持特定组织干细胞的体内平衡。进一步了解化学预防剂和干细胞生物学的作用机制将产生更好的化学预防方案，特别是可以推荐给高危人群。
