Mohan Amrutha, Raj R Reshma, Mohan Gayathri, K P Padmaja, Maliekal Tessy Thomas
Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
Centre for Doctoral Studies, Manipal Academy of Higher Education, Manipal, India.
Front Oncol. 2021 Apr 22;11:669250. doi: 10.3389/fonc.2021.669250. eCollection 2021.
In view of the importance of cancer stem cells (CSCs) in chemoresistance, metastasis and recurrence, the biology of CSCs were explored in detail. Based on that, several modalities were proposed to target them. In spite of the several clinical trials, a successful CSC-targeting drug is yet to be identified. The number of molecules screened and entered for clinical trial for CSC-targeting is comparatively low, compared to other drugs. The bottle neck is the lack of a high-throughput adaptable screening strategy for CSCs. This review is aimed to identify suitable reporters for CSCs that can be used to identify the heterogeneous CSC populations, including quiescent CSCs, proliferative CSCs, drug resistant CSCs and metastatic CSCs. Analysis of the tumor microenvironment regulating CSCs revealed that the factors in CSC-niche activates effector molecules that function as CSC markers, including pluripotency markers, CD133, ABCG2 and ALDH1A1. Among these factors OCT4, SOX2, NANOG, ABCG2 and ALDH1A1 are ideal for making reporters for CSCs. The pluripotency molecules, like OCT4, SOX2 and NANOG, regulate self-renewal, chemoresistance and metastasis. ABCG2 is a known regulator of drug resistance while ALDH1A1 modulates self-renewal, chemoresistance and metastasis. Considering the heterogeneity of CSCs, including a quiescent population and a proliferative population with metastatic ability, we propose the use of a combination of reporters. A dual reporter consisting of a pluripotency marker and a marker like ALDH1A1 will be useful in screening drugs that target CSCs.
鉴于癌症干细胞（CSCs）在化疗耐药性、转移和复发中的重要性，对CSCs的生物学特性进行了详细研究。在此基础上，提出了几种针对它们的方法。尽管进行了多项临床试验，但尚未确定一种成功的靶向CSC的药物。与其他药物相比，筛选并进入CSC靶向临床试验的分子数量相对较少。瓶颈在于缺乏一种适用于CSCs的高通量筛选策略。本综述旨在确定适用于CSCs的合适报告基因，可用于识别异质性CSC群体，包括静止CSCs、增殖性CSCs、耐药CSCs和转移性CSCs。对调节CSCs的肿瘤微环境的分析表明，CSC生态位中的因子激活了作为CSC标志物起作用的效应分子，包括多能性标志物、CD133、ABCG2和ALDH1A1。在这些因子中，OCT4、SOX2、NANOG、ABCG2和ALDH1A1是制备CSCs报告基因的理想选择。多能性分子，如OCT4、SOX2和NANOG，调节自我更新、化疗耐药性和转移。ABCG2是一种已知的耐药调节因子，而ALDH1A1调节自我更新、化疗耐药性和转移。考虑到CSCs的异质性，包括静止群体和具有转移能力的增殖群体，我们建议使用报告基因组合。由多能性标志物和ALDH1A1等标志物组成的双报告基因将有助于筛选靶向CSCs的药物。
