Journal
CANCER CELL INTERNATIONAL
Volume 14, Issue -, Pages -Publisher
BMC
DOI: 10.1186/1475-2867-14-18
Keywords
Transcription inhibition; Cancer therapy; Gene expression; RNA polymerase
Categories
Funding
- Programa de Apoyo a Proyectos de Investigacion e Inovacion Tecnologica (PAPIIT)/Universidad Nacional Autonoma de Mexico (UNAM)
- Consejo Nacional de Ciencia y Tecnologia (CONACYT)
- Miguel Aleman Foundation
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General transcription is required for the growth and survival of all living cells. However, tumor cells require extraordinary levels of transcription, including the transcription of ribosomal RNA genes by RNA polymerase I (RNPI) and mRNA by RNA polymerase II (RNPII). In fact, cancer cells have mutations that directly enhance transcription and are frequently required for cancer transformation. For example, the recent discovery that MYC enhances the transcription of the majority genes in the genome correlates with the fact that several transcription interfering drugs preferentially kill cancer cells. In recent years, advances in the mechanistic studies of the basal transcription machinery and the discovery of drugs that interfere with multiple components of transcription are being used to combat cancer. For example, drugs such as triptolide that targets the general transcription factors TFIIH and JQ1 to inhibit BRD4 are administered to target the high proliferative rate of cancer cells. Given the importance of finding new strategies to preferentially sensitize tumor cells, this review primarily focuses on several transcription inhibitory drugs to demonstrate that the basal transcription machinery constitutes a potential target for the design of novel cancer drugs. We highlight the drugs' mechanisms for interfering with tumor cell survival, their importance in cancer treatment and the challenges of clinical application.
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