Wei Wei, Lewis Michael T
Baylor College of MedicineLester and Sue Smith Breast Center, Houston, Texas, USADepartments of Molecular and Cellular BiologyRadiologyBaylor College of Medicine, One Baylor Plaza, BCM600, Room N1210, Houston, Texas 77030, USA Baylor College of MedicineLester and Sue Smith Breast Center, Houston, Texas, USADepartments of Molecular and Cellular BiologyRadiologyBaylor College of Medicine, One Baylor Plaza, BCM600, Room N1210, Houston, Texas 77030, USA.
Baylor College of MedicineLester and Sue Smith Breast Center, Houston, Texas, USADepartments of Molecular and Cellular BiologyRadiologyBaylor College of Medicine, One Baylor Plaza, BCM600, Room N1210, Houston, Texas 77030, USA Baylor College of MedicineLester and Sue Smith Breast Center, Houston, Texas, USADepartments of Molecular and Cellular BiologyRadiologyBaylor College of Medicine, One Baylor Plaza, BCM600, Room N1210, Houston, Texas 77030, USA Baylor College of MedicineLester and Sue Smith Breast Center, Houston, Texas, USADepartments of Molecular and Cellular BiologyRadiologyBaylor College of Medicine, One Baylor Plaza, BCM600, Room N1210, Houston, Texas 77030, USA
Endocr Relat Cancer. 2015 Jun;22(3):R135-55. doi: 10.1530/ERC-14-0447. Epub 2015 Apr 15.
Breast cancer is the most common cancer in women (excluding skin cancer), and it is the second leading cause of cancer-related deaths. Although conventional and targeted therapies have improved survival rates, there are still considerable challenges in treating breast cancer, including treatment resistance, disease recurrence, and metastasis. Treatment resistance can be either de novo - because of traits that tumor cells possess before treatment - or acquired - because of traits that tumor cells gain in response to treatment. A recently proposed mechanism of de novo resistance invokes the existence of a specialized subset of cancer cells defined as tumor-initiating cells (TICs), or cancer stem cells (CSCs). TICs have the capacity to self-renew and to generate new tumors that consist entirely of clonally derived cell types present in the parental tumor. There are data to suggest that TICs are resistant to many conventional cancer therapies and that they can survive treatment in spite of dramatic shrinkage of the tumor. Residual TICs can then eventually regrow, which results in disease relapse. It has also been hypothesized that TIC may be responsible for metastatic disease. If these hypotheses are correct, targeting TICs may be imperative for achieving a cure. In the present review, we discuss evidence for breast TICs and their apparent resistance to conventional chemotherapy and radiotherapy as well as to various targeted therapies. We also address the potential impact of breast TIC plasticity and metastatic potential on therapeutic strategies. Finally, we describe several genes and signaling pathways that appear to be important for TIC function and may represent promising therapeutic targets.
乳腺癌是女性中最常见的癌症（不包括皮肤癌），也是癌症相关死亡的第二大主要原因。尽管传统疗法和靶向疗法提高了生存率，但在治疗乳腺癌方面仍存在相当大的挑战，包括治疗耐药性、疾病复发和转移。治疗耐药性可以是原发性的——由于肿瘤细胞在治疗前就具有的特性——或者是获得性的——由于肿瘤细胞在对治疗的反应中获得的特性。最近提出的一种原发性耐药机制涉及一种特殊的癌细胞亚群的存在，这种亚群被定义为肿瘤起始细胞（TICs）或癌症干细胞（CSCs）。TICs具有自我更新的能力，并能产生完全由亲代肿瘤中存在的克隆衍生细胞类型组成的新肿瘤。有数据表明，TICs对许多传统癌症疗法具有抗性，并且尽管肿瘤显著缩小，它们仍能在治疗中存活。残留的TICs最终可能会重新生长，从而导致疾病复发。也有人推测TIC可能是转移性疾病的原因。如果这些假设是正确的，那么靶向TICs对于实现治愈可能至关重要。在本综述中，我们讨论了乳腺TICs的证据及其对传统化疗、放疗以及各种靶向疗法的明显抗性。我们还探讨了乳腺TIC可塑性和转移潜能对治疗策略的潜在影响。最后，我们描述了几个似乎对TIC功能很重要且可能代表有前景治疗靶点的基因和信号通路。
