The transcriptional stress response and its implications in cancer treatment

Abstract

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.

Keywords: Cancer therapy; Chemotherapy resistance; Pre-initiation complex; RNA polymerase II; Stress response; Transcription addiction; Transcription inhibitors.