Department of Health Sciences, Campus de las Lagunillas SN, University of Jaén, E-23071 Jaén, Spain.
Excellence Research Unit "Modeling Nature" (MNat), University of Granada, E-18016 Granada, Spain.
Int J Mol Sci. 2022 Aug 5;23(15):8720. doi: 10.3390/ijms23158720.
The increase in cancer incidences shows that there is a need to better understand tumour heterogeneity to achieve efficient treatments. Interestingly, there are several common features among almost all types of cancers, with chronic inflammation induction and deaminase dysfunctions singled out. Deaminases are a family of enzymes with nucleotide-editing capacity, which are classified into two main groups: DNA-based and RNA-based. Remarkably, a close relationship between inflammation and the dysregulation of these molecules has been widely documented, which may explain the characteristic intratumor heterogeneity, both at DNA and transcriptional levels. Indeed, heterogeneity in cancer makes it difficult to establish a unique tumour progression model. Currently, there are three main cancer models-stochastic, hierarchic, and dynamic-although there is no consensus on which one better resembles cancer biology because they are usually overly simplified. Here, to accurately explain tumour progression, we propose interactions among chronic inflammation, deaminases dysregulation, intratumor genetic heterogeneity, cancer phenotypic plasticity, and even the previously proposed appearance of cancer stem-like cell populations in the edges of advanced solid tumour masses (instead of being the cells of origin of primary malignancies). The new tumour development model proposed in this study does not contradict previously accepted models and it may open up a window to interesting therapeutic approaches.
癌症发病率的增加表明，有必要更好地了解肿瘤异质性，以实现有效的治疗。有趣的是，几乎所有类型的癌症都有几个共同的特征，其中包括慢性炎症的诱导和脱氨酶功能障碍。脱氨酶是一类具有核苷酸编辑能力的酶，可分为两类：基于 DNA 的和基于 RNA 的。值得注意的是，炎症与这些分子的失调之间的密切关系已被广泛记录在案，这可能解释了肿瘤内的特征异质性，无论是在 DNA 还是转录水平上。事实上，癌症的异质性使得建立一个独特的肿瘤进展模型变得困难。目前，有三种主要的癌症模型——随机、层次和动态——尽管对于哪种模型更能反映癌症生物学尚无共识，因为它们通常过于简化。在这里，为了准确地解释肿瘤的进展，我们提出了慢性炎症、脱氨酶失调、肿瘤内遗传异质性、癌症表型可塑性之间的相互作用，甚至是之前提出的癌症干细胞样细胞群在晚期实体瘤边缘出现的现象（而不是原发性恶性肿瘤的起源细胞）。本研究提出的新肿瘤发展模型并不与以前接受的模型相矛盾，它可能为有趣的治疗方法开辟了一扇窗。
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