Abstract

Targeting Chromatin Remodeling and Bromodomain in Cancer

Rakesh Kumar, Distinguished Professor and National Chair in Cancer Research, Rajiv Gandhi Centre for Biotechnology

Fundamental to the process of cancer progression and metastasis is the ability of cancer cells to respond to both extra- and intra-cellular milieu and translate resulting signals for the benefit of gene expression in an orderly manner through chromatin remodeling complexes. The functional outcome of the chromatin remodeling complexes is primarily influenced by the nature of enzymes and coregulatory proteins and its combinatorial post-translational modifications, among other mechanisms. At the molecular level, the process of gene expression in cancer cells is regulated by epigenomic interactions of chromatin remodelers, bromodomain-containing proteins, and histones in the context of target gene chromatin. Therefore, any dysfunction of genes for chromatin remodeling proteins and chromatin-interacting proteins with bromodomains may inappropriately alter the steady state levels of regulatory genes with roles in oncogenesis. Recent advances in cancer epigenetic re-emphasize the significance of studying epigenomic regulation of gene expression for identifying the next generation of cancer therapeutic targets. Consistent with this notion, there is a widespread dysregulation of chromatin remodeling and bromodomain-containing proteins in human cancer. Hence, specific chromatin remodeling factors and/or bromodomain-containing proteins have emerged as promising candidates for the development of anti-cancer therapeutics either alone or as a part of combination therapy. The lecture will provide an overview of the current status and approaches to target such molecules with a hope to develop superior anti-cancer agents.