Faculty of Science, University of Oradea, Oradea 410087, Romania.
School of Physical Sciences, The University of Adelaide, SA 5005, Australia.
Sci Rep. 2016 Aug 30;6:32332. doi: 10.1038/srep32332.
Head and neck cancers (HNC), like most solid tumours, contain a subpopulation of cancer stem cells (CSC) that are commonly responsible for treatment failure. Conventional therapies are unsuccessful in controlling CSCs, thus novel, targeting therapies are needed. A promising agent is ATRA (All-trans-retinoic acid) that was shown to induce CSC differentiation, cell cycle redistribution and CSCs radiosensitisation. To add to the limited data, this work simulated the effects of ATRA on a virtual HNC and evaluated tumour response to radiotherapy. A Monte Carlo technique was employed to grow a HNC consisting of all lineages of cancer cells. The biologically realistic input parameters led to a pre-treatment CSC population of 5.9%. The Linear Quadratic model was employed to simulate radiotherapy. ATRA-induced differentiation, cell arrest and apoptosis were modelled, based on literature data. While the effect of differentiation was marginal, the strongest influence on CSC subpopulation was displayed by ATRA's cell arrest effect via an exponential behaviour of the dose-response curve. The apoptotic effect induced by ATRA shows linear correlation between the percentage of apoptotic cells and dose required to eradicate CSCs. In conclusion, ATRA is a potent CSC-targeting agent with viable impact on tumour control when combined with radiotherapy.
头颈部癌症（HNC）与大多数实体瘤一样，含有一小部分癌症干细胞（CSC），这些细胞通常是导致治疗失败的原因。传统疗法无法控制 CSC，因此需要新的靶向治疗方法。一种有前途的药物是 ATRA（全反式维甲酸），它已被证明可以诱导 CSC 分化、细胞周期再分布和 CSCs 放射增敏。为了增加有限的数据，这项工作模拟了 ATRA 对头颈部癌症的影响，并评估了肿瘤对放射治疗的反应。采用蒙特卡罗技术来生长由所有癌细胞谱系组成的头颈部癌症。生物学上合理的输入参数导致治疗前 CSC 群体为 5.9%。采用线性二次模型来模拟放射治疗。基于文献数据，对 ATRA 诱导的分化、细胞阻滞和细胞凋亡进行了建模。虽然分化的效果微不足道，但 ATRA 通过剂量反应曲线的指数行为对细胞阻滞的影响对 CSC 亚群的影响最大。ATRA 诱导的细胞凋亡与消灭 CSC 所需的剂量之间呈线性相关。总之，ATRA 是一种有效的 CSC 靶向药物，与放射治疗联合使用时对肿瘤控制具有可行的影响。
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