Transcriptional corepressors in cancer

Emerging targets for therapeutic intervention


  • Petros D. Grivas MD, PhD,

    1. Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan
    Search for more papers by this author
  • Athanasios G. Papavassiliou MD, PhD

    Corresponding author
    1. Department of Biological Chemistry, University of Athens Medical School, Athens, Greece
    • Department of Biological Chemistry, Medical School, University of Athens, 75, M. Asias Street, GR-11527 Athens, Greece

    Search for more papers by this author
    • Fax: (011) 30-210-779-1207


The normal cell transcriptional process entails a high degree of combinatorial effects and time-dependent “flexibility” to translate cellular signaling into differential gene expression levels. Transcriptional corepressors can function as histone-modifying enzymes to regulate epigenetic events, modulate chromatin structure, and hence control transcriptional activity. Various corepressor complexes have been described; qualitative and quantitative alterations of corepressors can crucially influence the transcriptional output of both normal and malignant cells. Because these molecules can exert epigenetic control of tumorigenic signaling pathways, they can be considered potential regulators of cancer cell-related phenomena. Alterations of the expression level and/or function of transcriptional corepressors have been reported in a wide range of human cancers; thus, corepressors may present rational therapeutic targets as well as potential biomarkers of response to selective therapeutic interventions. Deeper insights into the context-specific and time-specific physical connections among transcription factors, coregulators, and gene regulatory elements, as well as epigenetic modifications, and their interactions, can enhance the capacity to interfere with small molecules that may restore the normal transcriptome/interactome in a cancer cell. There are several conceivable mechanisms of corepressor targeting in cancer that create enthusiasm. However, design, discovery, and testing of such innovative treatment approaches require extensive elaboration before they can achieve practical implementation in the clinic. Cancer 2013. © 2012 American Cancer Society.