Targeting key proteins involved in transcriptional regulation for cancer therapy: Current strategies and future prospective

Abstract

The key proteins involved in transcriptional regulation play convergent roles in cellular homeostasis, and their dysfunction mediates aberrant gene expressions that underline the hallmarks of tumorigenesis. As tumor progression is dependent on such abnormal regulation of transcription, it is important to discover novel chemical entities as antitumor drugs that target key tumor‐associated proteins involved in transcriptional regulation. Despite most key proteins (especially transcription factors) involved in transcriptional regulation are historically recognized as undruggable targets, multiple targeting approaches at diverse levels of transcriptional regulation, such as epigenetic intervention, inhibition of DNA‐binding of transcriptional factors, and inhibition of the protein–protein interactions (PPIs), have been established in preclinically or clinically studies. In addition, several new approaches have recently been described, such as targeting proteasomal degradation and eliciting synthetic lethality. This review will emphasize on accentuating these developing therapeutic approaches and provide a thorough conspectus of the drug development to target key proteins involved in transcriptional regulation and their impact on future oncotherapy.

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“…Tumor metastasis plays a key role in tumor development and deterioration and is responsible for >90% of cancer deaths. , Therefore, compounds ( 5j , 5m , 6f , and 6g ) with potent antiproliferative activities as well as high binding affinities were subjected to migration experiments to assess their effects against osteosarcoma cell migration. As listed in Figure A, compounds 5j , 6f , and 6g showed potent antimigration efficacy with IC 50 values of <0.60 μM against 143B cells, which is approximately 8–10 times better than that of positive control 1d .…”

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