Department of Health Sciences, University of Jaén, Jaén E-23071, Spain.
Excellence Research Unit "Modeling Nature" (MNat), University of Granada, Granada, E- 18016, Spain; Biopathology and Regenerative Medicine Institute (IBIMER), Centre for Biomedical Research, University of Granada, Granada E-18100, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, E- 18016, Spain; Biosanitary Research Institute of Granada (ibs.GRANADA), University Hospitals of Granada-University of Granada, Granada, E-18071, Spain.
Crit Rev Oncol Hematol. 2018 Nov;131:35-45. doi: 10.1016/j.critrevonc.2018.08.004. Epub 2018 Aug 28.
The lack of an effective treatment against cancer is not only due to its huge heterogeneity, but also to the fact that we don't have an answer to the question on how cancer originates. Among the proposed models to explain the development of cancer, the hierarchical model has been widely accepted. Nevertheless, this model fails to explain several experimental observations such as the cancer stem cells (CSCs) location inside a tumour or the differences between primary and metastatic tumours. Moreover, increasing evidence shows that the CSC phenotype is not a rigid state. Here, we present a critical review on the assumed tumour development models emphasizing the relevance of the dynamic and changing nature of cancer and the CSCs population in which the tumour microenvironment plays a crucial role and we propose a new model of tumour origin that could have an impact on new therapeutic strategies.
癌症缺乏有效治疗方法的原因不仅在于其巨大的异质性，还在于我们还没有回答癌症起源的问题。在解释癌症发展的提出的模型中，等级模型得到了广泛的认可。然而，该模型无法解释肿瘤内癌症干细胞 (CSC) 的位置或原发性和转移性肿瘤之间的差异等几个实验观察结果。此外，越来越多的证据表明 CSC 表型不是一种固定状态。在这里，我们对假设的肿瘤发展模型进行了批判性的回顾，强调了肿瘤和 CSC 群体的动态和变化性质的重要性，其中肿瘤微环境起着至关重要的作用，并提出了一种新的肿瘤起源模型，可能对新的治疗策略产生影响。
