Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, 620 University Avenue, Toronto, Ontario, Canada M5G 2M9.
Cancer Lett. 2012 Apr 28;317(2):115-26. doi: 10.1016/j.canlet.2011.11.028. Epub 2011 Nov 26.
The recognition of breast cancer as a molecularly heterogeneous disease where individual tumors display cellular hierarchy containing "primitive" stem-like tumor-initiating cells (TICs) and their derivatives, has directed efforts towards the development of personalized targeted therapies based on the characteristics of individual cancers. Targeted therapies are designed to attack processes that uniquely support cancer progression, including maintenance of TICs, invasion, metastasis, cell survival and tumor-related angiogenesis and thereby result in less collateral damage than conventional chemotherapy. Recently, it has been demonstrated that pathways such as Hedgehog (Hh), Wnt and Notch, which regulate development during embryonic life and somatic stem cells (SCs) in the adult organism, can be reactivated in malignancies and support the TIC compartment. Herein, we review the role of developmental pathways in stem cell biology and provide an up-to-date survey of pre-clinical and clinical trials of novel strategies to target them.
乳腺癌被认为是一种分子异质性疾病，其中单个肿瘤显示出细胞层次结构，包含“原始”的干细胞样肿瘤起始细胞（TICs）及其衍生物，这促使人们致力于开发基于个体癌症特征的个性化靶向治疗。靶向治疗旨在攻击独特地支持癌症进展的过程，包括 TIC 的维持、侵袭、转移、细胞存活以及与肿瘤相关的血管生成，从而比传统化疗造成的附带损伤更小。最近已经证明，在胚胎发育过程中以及成年生物体中的体干细胞（SCs）中调节发育的通路，如 Hedgehog（Hh）、Wnt 和 Notch 等，在恶性肿瘤中可以被重新激活，并支持 TIC 区室。在此，我们综述了发育途径在干细胞生物学中的作用，并提供了针对这些途径的新策略的临床前和临床试验的最新调查。
