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.