Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, 62210 Cuernavaca, Mor., Mexico.
Departamento de Genética del Desarrollo y Fisiología Molecular, Instituto de Biotecnología, Universidad Nacional Autónoma de México, 62210 Cuernavaca, Mor., Mexico.
Biochim Biophys Acta Rev Cancer. 2021 Dec;1876(2):188620. doi: 10.1016/j.bbcan.2021.188620. Epub 2021 Aug 26.
Cancer cells require high levels of transcription to survive and maintain their cancerous phenotype. For several years, global transcription inhibitors have been used in the treatment of cancer. However, recent advances in understanding the functioning of the basal transcription machinery and the discovery of new drugs that affect the components of this machinery have generated a new boom in the use of this type of drugs to treat cancer. Inhibiting transcription at the global level in the cell generates a stress situation in which the cancer cell responds by overexpressing hundreds of genes in response to this transcriptional stress. Many of these over-transcribed genes encode factors that may be involved in the selection of cells resistant to the treatment and with a greater degree of malignancy. In this study, we reviewed various examples of substances that inhibit global transcription, as well as their targets, that have a high potential to be used against cancer. We also analysed what kinds of genes are overexpressed in the response to transcriptional stress by different substances and finally we discuss what types of studies are necessary to understand this type of stress response to have more tools to fight cancer.
癌细胞需要高水平的转录来存活并维持其癌变表型。多年来，全球转录抑制剂一直被用于癌症治疗。然而，近年来对基础转录机制功能的深入了解，以及发现影响该机制组件的新药，为使用这类药物治疗癌症带来了新的热潮。在细胞的全转录水平上抑制转录会产生一种应激状态，癌细胞会通过过度表达数百个基因来应对这种转录应激。其中许多过度转录的基因编码的因子可能参与了对治疗有抗性的细胞的选择，并且具有更高的恶性程度。在这项研究中，我们回顾了各种抑制全转录的物质及其靶点的例子，这些物质具有很高的潜力可用于对抗癌症。我们还分析了不同物质对转录应激的反应中哪些基因过度表达，并最终讨论了需要进行哪些类型的研究来理解这种应激反应，以便拥有更多对抗癌症的工具。
