Séronie-Vivien Sophie
Service de biochimie, de biologie moléculaire et de biotechnologie, Institut Claudius Regaud et Faculté des sciences pharmaceutiques, Université Paul Sabatier, Toulouse III, France.
Ann Biol Clin (Paris). 2014 Mar-Apr;72(2):153-77. doi: 10.1684/abc.2014.0945.
Circulating tumor cells (CTCs) can be detected in the blood of patients with nearly all types of locally and metastatic adenocarcinomas. CTCs are epithelial cells whose release from a primitive tumor or a metastatic localization may be mediated by an epithelial-mesenchymal transition. Their pro-metastatic potential is still under debate because their phenotypes may be very heterogeneous, even within the same patient (expression of stem-cells markers, apoptotic status...). They often exhibit discrepancies with the primitive tumor, especially concerning the molecular basis of sensitivity/resistance to targeted therapies (expression of HER2 and hormone receptors, mutations responsible for resistance to tyrosine-kinase inhibitors). Many methods for CTCs analysis are commercially available but very few are evaluated and standardized enough for clinical applications. The CellSearch device is the only one which is validated by the FDA for managing metastatic breast, prostate and colo-rectal cancer. It was used in most of the studies having demonstrated the prognostic and predictive value of CTCs in many tumoral localizations. Other studies are wanted to assess the ability of CTCs to optimize the therapeutic choices, to monitor drug efficiency in real-time as well as to become a surrogate end-point for evaluation of new therapies. Beyond CTCs enumeration, their biological features will need to be investigated.
在几乎所有类型的局部和转移性腺癌患者的血液中都能检测到循环肿瘤细胞(CTC)。CTC是上皮细胞,其从原发性肿瘤或转移部位释放可能由上皮-间质转化介导。它们的促转移潜力仍存在争议,因为即使在同一患者体内,其表型也可能非常异质(干细胞标志物的表达、凋亡状态等)。它们常常与原发性肿瘤存在差异,尤其是在对靶向治疗的敏感性/耐药性的分子基础方面(HER2和激素受体的表达、对酪氨酸激酶抑制剂耐药的突变)。有许多用于CTC分析的方法在市场上有售,但对于临床应用而言,经过充分评估和标准化的却很少。CellSearch设备是唯一经美国食品药品监督管理局(FDA)验证可用于管理转移性乳腺癌、前列腺癌和结直肠癌的设备。在大多数证明CTC在许多肿瘤部位具有预后和预测价值的研究中都使用了该设备。还需要其他研究来评估CTC优化治疗选择、实时监测药物疗效以及成为评估新疗法替代终点的能力。除了对CTC进行计数外,还需要研究它们的生物学特性。