Groner Bernd, Vafaizadeh Vida, Brill Boris, Klemmt Petra
Georg Speyer Haus, Institute for Biomedical Research, Frankfurt, Germany.
Womens Health (Lond). 2010 Mar;6(2):205-19. doi: 10.2217/whe.10.5.
Breast cancer remains a significant public health problem despite advances in the understanding of the molecular and cellular events that underlie the disease. Crucial pathways regulating the cell cycle, proliferation and survival of breast cancer cells have been investigated and aberrant components of these pathways have been exploited as new drug targets. However, the mortality from breast cancer is only slowly declining. Recently, a model has been proposed that might explain the heterogeneous biological features of breast cancer cell populations and their differential response to therapeutic agents, which has interesting implications for further progress in therapy. This model links the emergence of breast cancer cells to stem cells and progenitors, an observation originally made in other cancer entities. It hypothesizes that the tumors originate from a small population of undifferentiated cells. These cells can undergo self-renewal and are able to generate a large number of partially differentiated cells, which constitute the bulk of the tumor. These cancer stem cells resemble adult stem and progenitor cells found in the normal breast, but are deregulated in their patterns of proliferation and differentiation. They could originate from normal stem cells or from more differentiated progenitors and lose their normal growth restraints through a series of oncogenic mutations that deregulate a small number of central signaling pathways. If breast cancer really is a stem and progenitor cell disease, this will have important implications for the understanding of the emergence of cancer cells. A combination of the cell-type of origin, stem cells, early or late progenitors and the particular oncogenic mutations acquired could provide a new classification of the different types of breast cancer. These parameters might determine the mechanisms of cancer progression and the responsiveness of patients to drug treatment. Stem cell-specific features could possibly be exploited as innovative drug targets.
尽管在对乳腺癌潜在的分子和细胞事件的理解方面取得了进展，但乳腺癌仍然是一个重大的公共卫生问题。调控乳腺癌细胞周期、增殖和存活的关键信号通路已得到研究，这些信号通路中的异常成分已被开发为新的药物靶点。然而，乳腺癌死亡率仅在缓慢下降。最近，有人提出了一个模型，该模型可能解释乳腺癌细胞群体的异质性生物学特征及其对治疗药物的不同反应，这对治疗的进一步进展具有有趣的启示。该模型将乳腺癌细胞的出现与干细胞和祖细胞联系起来，这一观察最初是在其他癌症实体中发现的。它假设肿瘤起源于一小群未分化细胞。这些细胞能够自我更新，并能够产生大量部分分化的细胞，这些细胞构成了肿瘤的主体。这些癌症干细胞类似于正常乳腺中发现的成体干细胞和祖细胞，但在增殖和分化模式上失调。它们可能起源于正常干细胞或更分化的祖细胞，并通过一系列使少数核心信号通路失调的致癌突变而失去正常的生长限制。如果乳腺癌真的是一种干细胞和祖细胞疾病，这将对理解癌细胞的出现具有重要意义。起源细胞类型（干细胞、早期或晚期祖细胞）与获得的特定致癌突变的组合，可能会为不同类型的乳腺癌提供一种新的分类方法。这些参数可能决定癌症进展的机制以及患者对药物治疗的反应。干细胞特异性特征可能被开发为创新的药物靶点。
