Signal Transduction Lab, Queensland Institute of Medical Research, 300 Herston Road, Brisbane, Queensland 4006, Australia.
Carcinogenesis. 2011 May;32(5):650-8. doi: 10.1093/carcin/bgr028. Epub 2011 Feb 10.
The clinical and pathologic heterogeneity of human breast cancer has long been recognized. Now, molecular profiling has enriched our understanding of breast cancer heterogeneity and yielded new prognostic and predictive information. Despite recent therapeutic advances, including the HER2-specific agent, trastuzumab, locoregional and systemic disease recurrence remain an ever-present threat to the health and well being of breast cancer survivors. By definition, disease recurrence originates from residual treatment-resistant cells, which regenerate at least the initial breast cancer phenotype. The discovery of the normal breast stem cell has re-ignited interest in the identity and properties of breast cancer stem-like cells and the relationship of these cells to the repopulating ability of treatment-resistant cells. The cancer stem cell model of breast cancer development contrasts with the clonal evolution model, whereas the mixed model draws on features of both. Although the origin and identity of breast cancer stem-like cells is contentious, treatment-resistant cells survive and propagate only because aberrant and potentially druggable signaling pathways are recruited. As a means to increase the rates of breast cancer cure, several approaches to specific targeting of the treatment-resistant cell population exist and include methods for addressing the problem of radioresistance in particular.
人类乳腺癌的临床和病理异质性早已为人所知。现在，分子谱分析丰富了我们对乳腺癌异质性的理解，并提供了新的预后和预测信息。尽管最近在治疗方面取得了进展，包括 HER2 特异性药物曲妥珠单抗，但局部和全身疾病的复发仍然对乳腺癌幸存者的健康和幸福构成了持续的威胁。根据定义，疾病的复发源于残留的治疗耐药细胞，这些细胞至少会再生最初的乳腺癌表型。正常乳腺干细胞的发现重新激发了人们对乳腺癌类干细胞的特性和特性的兴趣，以及这些细胞与治疗耐药细胞的再增殖能力的关系。乳腺癌发展的癌症干细胞模型与克隆进化模型相反，而混合模型则借鉴了两者的特征。尽管乳腺癌类干细胞的起源和特性存在争议，但只有通过招募异常且潜在可靶向的信号通路，治疗耐药细胞才能存活和增殖。作为提高乳腺癌治愈率的一种手段，存在几种针对治疗耐药细胞群体的特定靶向方法，包括解决特别是放射性耐药问题的方法。
