Cancer Drug Resistance Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Expression Regulation in Cancer Group, Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal.
Int J Cancer. 2014 Mar 15;134(6):1270-8. doi: 10.1002/ijc.28478. Epub 2013 Oct 21.
Tumour drug resistance is a major issue in the management of lung cancer patients as almost all lung tumours are either intrinsically resistant or quickly develop acquired resistance to chemotherapeutic drugs. Cancer drug resistance has recently been linked, at least in part, to the existence of cancer stem-like cells (CSLCs), a small sub-population of cells within the tumour that possess stem-like properties. CSLCs are often isolated by fluorescence activated cell sorting (FACS) according to the expression of certain stem-like cell membrane markers. Conflicting results regarding the specificity of particular stem cell surface markers for isolating CSLCs have, however, been recently reported. Therefore, alternative strategies enabling the identification and study of CSLCs should be considered, particularly in tumour types where appropriate stem cell markers are not well established and validated, like in lung cancer. In this article, we review data indicating therapy-selection as a valid approach for putative lung CSLCs enrichment. We believe that this strategy would be determinant for correctly assessing and characterising the sub-populations of CSLCs that are able to survive chemo or radiotherapy regimens and, at the same time, also have the ability to recapitulate and sustain tumour growth. Using therapy-induced enrichment of CSLCs may, therefore, prove to be an extremely useful method for studying CSLCs and provide new clues regarding potential therapeutic targets for their efficient elimination, which will undoubtedly play a decisive role in improving lung cancer patients' survival.
肿瘤耐药性是肺癌患者管理中的一个主要问题,因为几乎所有的肺癌肿瘤要么天生耐药,要么很快对化疗药物产生获得性耐药。最近,癌症耐药性至少部分与癌症干细胞样细胞(CSLCs)的存在有关,CSLCs 是肿瘤内具有干细胞样特性的一小部分细胞。CSLCs 通常通过荧光激活细胞分选(FACS)根据某些干细胞样细胞膜标记物的表达来分离。然而,最近有报道称,关于特定干细胞表面标记物用于分离 CSLCs 的特异性存在矛盾的结果。因此,应该考虑其他能够识别和研究 CSLCs 的替代策略,特别是在适当的干细胞标记物尚未得到很好的建立和验证的肿瘤类型中,如肺癌。在本文中,我们回顾了表明治疗选择是富集潜在肺 CSLCs 的有效方法的数据。我们认为,这种策略对于正确评估和表征能够耐受化疗或放疗方案并同时具有重新复制和维持肿瘤生长能力的 CSLC 亚群至关重要。因此,使用治疗诱导的 CSLCs 富集可能被证明是研究 CSLCs 的一种非常有用的方法,并为其有效消除提供新的线索,这无疑将在提高肺癌患者的生存率方面发挥决定性作用。