肿瘤细胞对各种治疗方法产生抗性的发展是肿瘤学治疗的一个重要问题，降低了治疗的有效性。二十多年来，通过对肿瘤细胞在不同对电离辐射和化疗药物敏感性之间进行比较的转录组研究，以确定背后的原因和机制，从而识别发展治疗抗性的机制已经展开。然而，这些研究的结果千差万别且常常相互矛盾。我们假设对大量这类研究进行系统分析将为肿瘤细胞产生治疗抗性的机制提供新的知识。我们比较了98篇论文中发表的123个差异表达基因(DEGs)列表，结果显示研究结果的一致性非常低。按类型的遗传毒剂和肿瘤类型对数据进行分组并没有增加相似性。最常见的过度表达基因是编码转运蛋白ABCB1和抗病毒防御蛋白IFITM1的基因。我们提出一个假设，即后者的过度表达在抗性的发展中的作用可能不仅与增殖刺激有关，还与外泌体通讯的限制有关，从而导致旁观者效应的减少。在下调的DEGs中，BNIP3出现的频率最高。在对非铂类遗传毒剂具有耐药性的细胞中，BNIP3和BNIP3L的表达通常被抑制，然而在对电离辐射具有耐药性的细胞中表达增加。这些观察结果可能通过这些基因产物对细胞存活、凋亡和自噬的二元效应进行中介。这些综合数据还表明，即使像抑制凋亡和增加增殖这样明显的机制也并非普遍存在，而是显示出多方向变化。版权所有 © 2023 Elsevier B.V. 保留所有权利。

The development of resistance by tumor cells to various types of therapy is a significant problem that decreases the effectiveness of oncology treatments. For more than two decades, comparative transcriptomic studies of tumor cells with different sensitivities to ionizing radiation and chemotherapeutic agents have been conducted in order to identify the causes and mechanisms underlying this phenomenon. However, the results of such studies have little in common and often contradict each other. We have assumed that a systematic analysis of a large number of such studies will provide new knowledge about the mechanisms of development of therapeutic resistance in tumor cells. Our comparison of 123 differentially expressed gene (DEG) lists published in 98 papers suggests a very low degree of consistency between the study results. Grouping the data by type of genotoxic agent and tumor type did not increase the similarity. The most frequently overexpressed genes were found to be those encoding the transport protein ABCB1 and the antiviral defense protein IFITM1. We put forward a hypothesis that the role played by the overexpression of the latter in the development of resistance may be associated not only with the stimulation of proliferation, but also with the limitation of exosomal communication and, as a result, with a decreasing of the bystander effect. Among downregulated DEGs, BNIP3 was observed most frequently. The expression of BNIP3, together with BNIP3L, is often suppressed in cells resistant to non-platinum genotoxic chemotherapeutic agents, whereas it is increased in cells resistant to ionizing radiation. These observations are likely to be mediated by the binary effects of these gene products on survival, and regulation of apoptosis and autophagy. The combined data also show that even such obvious mechanisms as inhibition of apoptosis and increase of proliferation are not universal but show multidirectional changes.Copyright © 2023 Elsevier B.V. All rights reserved.