Abstract
Transcription and translation are fundamental cellular processes that govern the protein production of cells. These processes are generally up regulated in cancer cells, to maintain the enhanced metabolism and proliferative state of these cells. As such cancerous cells can be susceptible to transcription and translation inhibitors. There are numerous druggable proteins involved in transcription and translation which make lucrative targets for cancer drug development. In addition to proteins, recent years have shown that the “undruggable” transcription factors and RNA molecules can also be targeted to hamper the transcription or translation in cancer. In this review, we summarize the properties and function of the transcription and translation inhibitors that have been tested and developed, focusing on the advances of the last 5 years. To complement this, we also discuss some of the recent advances in targeting oncogenes tightly controlling transcription including transcription factors and KRAS. In addition to natural and synthetic compounds, we review DNA and RNA based approaches to develop cancer drugs. Finally, we conclude with the outlook to the future of the development of transcription and translation inhibitors.
Highlights
Cancer refers to a large group of diseases of uncontrolled cell growth and division where a general cure or containment is nowhere to be seen
The DNA binding site of transcription factors with its positively charged environment is a difficult target for developing small-molecule inhibitors, and most of the recent efforts have been aimed for the protein-protein interaction (PPI) inhibition, such as RG7388 (Arkin et al, 2014; Zhong et al, 2019)
There have been a few clinical successes in their development, such as the cyclin-dependent kinase (CDK) inhibitors, especially in combination with other chemotherapeutics. Targeting these central cellular processes has advantages to be more directed to cancer cells than nonspecific chemotherapeutic agents such as cisplatin
Summary
Cancer refers to a large group of diseases of uncontrolled cell growth and division where a general cure or containment is nowhere to be seen. While chemotherapy is directed to the inhibition of cell mitosis or inducing autophagy, targeted small molecules inhibitors act on the transcription and translation processes. CX-5461 CX-5461 (Figure 2) is the first selective Pol I inhibitor that has finished phase I clinical trials with promising results in advanced hematological cancers (Khot et al, 2019).
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