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Targeting Transcription Factors in Cancer

2015; Elsevier BV; Volume: 1; Issue: 1 Linguagem: Inglês

10.1016/j.trecan.2015.07.001

2405-8033

Anand S. Bhagwat, Christopher R. Vakoc,

Ubiquitin and proteasome pathways

TFs are commonly deregulated in the pathogenesis of human and are a major class of cancer cell dependencies. This makes TFs attractive targets for cancer therapy. Drugs that target nuclear hormone receptors are among the most impactful targeted therapies in all of oncology. Insights into their mechanism of action and mechanisms of resistance have illuminated fundamental concepts of TF-targeting therapeutics. Therapeutic targeting of general transcriptional cofactors can lead to remarkable efficacy in animal cancer models with surprisingly little toxicity to normal tissues. Chemical targeting of TFs for proteolysis is among the few curative strategies in cancer therapeutics today and is an emerging approach to suppress intractable protein targets. Transcription factors (TFs) are commonly deregulated in the pathogenesis of human cancer and are a major class of cancer cell dependencies. Consequently, targeting of TFs can be highly effective in treating particular malignancies, as highlighted by the clinical efficacy of agents that target nuclear hormone receptors. In this review we discuss recent advances in our understanding of TFs as drug targets in oncology, with an emphasis on the emerging chemical approaches to modulate TF function. The remarkable diversity and potency of TFs as drivers of cell transformation justifies a continued pursuit of TFs as therapeutic targets for drug discovery. Transcription factors (TFs) are commonly deregulated in the pathogenesis of human cancer and are a major class of cancer cell dependencies. Consequently, targeting of TFs can be highly effective in treating particular malignancies, as highlighted by the clinical efficacy of agents that target nuclear hormone receptors. In this review we discuss recent advances in our understanding of TFs as drug targets in oncology, with an emphasis on the emerging chemical approaches to modulate TF function. The remarkable diversity and potency of TFs as drivers of cell transformation justifies a continued pursuit of TFs as therapeutic targets for drug discovery.