Division of Medical Oncology, Sapienza University of Rome, Rome, Italy.
Curr Cancer Drug Targets. 2010 Aug;10(5):496-508. doi: 10.2174/156800910791517154.
The cancer stem cell (CSC) hypothesis provides an attractive model of tumour development and progression, holding that solid tumours are hierarchically organized and sustained by a minority of the tumour cell population with stem cell properties, such as self-renewal, tumorigenicity and multilineage differentiation capacity. Therapeutic resistance, underlying tumour recurrence and the lack of curative treatments in metastatic disease, raise the question if conventional anticancer therapies target the right cells. Indeed, these treatments might miss CSCs, which represent a more chemoresistant and radioresistant subpopulation within cancer. Recently, a direct link between the epithelial-mesenchymal transition process and the gain of stem cell competence were demonstrated in cultured breast cells. In particular, it was shown that the induction of EMT program not only allow cancer cells to disseminate from the primary tumor, but also promotes their self-renewal capability. Furthermore, the expression of stemness and EMT markers in CTCs were associated with resistance to conventional anti-cancer therapies and treatment failure, highlighting the urgency of improving tools for detecting and eliminating minimal residual disease.
癌症干细胞(CSC)假说为肿瘤的发生和发展提供了一个有吸引力的模型,认为实体瘤是由具有干细胞特性的肿瘤细胞的少数群体分层组织和维持的,例如自我更新、致瘤性和多能分化能力。治疗耐药性、肿瘤复发的潜在原因以及转移性疾病缺乏治愈性治疗,这引发了一个问题,即传统的抗癌疗法是否针对正确的细胞。事实上,这些治疗方法可能会错过 CSC,CSC 是癌症中更具化疗耐药性和放射抗性的亚群。最近,在培养的乳腺细胞中证明了上皮-间充质转化过程与获得干细胞能力之间存在直接联系。具体来说,已经表明 EMT 程序的诱导不仅允许癌细胞从原发性肿瘤扩散,而且还促进了它们的自我更新能力。此外,CSC 中干细胞和 EMT 标志物的表达与对传统抗癌疗法的耐药性和治疗失败相关,这凸显了改进用于检测和消除微小残留疾病的工具的紧迫性。