TY - JOUR
TI - Targeting the interplay between hdacs and dna damage repair for myeloma therapy
AU - Gkotzamanidou, M.
AU - Terpou, E.
AU - Kentepozidis, N.
AU - Terpos, E.
JO - International Journal of Molecular Sciences
PY - 2021
VL - 22
TODO - 19
SP - null
PB - MDPI
SN - 1422-0067
TODO - 10.3390/ijms221910406
TODO - histone deacetylase;  histone deacetylase inhibitor;  histone deacetylase;  histone deacetylase inhibitor;  tumor protein, base excision repair;  cancer therapy;  carcinogenesis;  DNA cross linking;  DNA damage;  DNA damage response;  DNA repair;  drug targeting;  epigenetics;  genomic instability;  histone acetylation;  homologous recombination;  human;  multiple myeloma;  nonhomologous end joining repair;  nonhuman;  nucleotide excision repair;  plasma cell;  regulatory mechanism;  Review;  animal;  DNA repair;  drug effect;  gene expression regulation;  genetic epigenesis;  hematologic disease;  immunology;  metabolism;  multiple myeloma;  pathology, Animals;  DNA Damage;  DNA Repair;  Epigenesis, Genetic;  Gene Expression Regulation, Neoplastic;  Hematologic Neoplasms;  Histone Deacetylase Inhibitors;  Histone Deacetylases;  Humans;  Multiple Myeloma;  Neoplasm Proteins
TODO - Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells, and accounts for 10% of all hematologic malignancies and 1% of all cancers. MM is characterized by genomic instability which results from DNA damage with certain genomic rearrangements being prognostic factors for the disease and patients’ clinical response. Following genotoxic stress, the evolutionary conserved DNA damage response (DDR) is activated and, in turn, coordinates DNA repair with cell‐cycle events. However, the process of carcinogenesis cannot be attributed only to the genetic alterations, but also involves epigenetic processes. Regulation of expression and activity of key players in DNA repair and checkpoint proteins are essential and mediated partly by post-translational modifications (PTM), such as acetylation. Crosstalk between different PTMs is im-portant for regulation of DNA repair pathways. Acetylation, which is mediated by acetyltransfer-ases (HAT) and histone deacetylases (HDAC), not only affects gene expression through its modulation of histone tails but also has recently been implicated in regulating non‐histone proteins. Currently, several HDAC inhibitors (HDACi) have been developed both in pre‐clinical and clinical studies, with some of them exhibiting significant anti‐MM activities. Due to reversibility of epigenetic changes during the evolutionary process of myeloma genesis, the potency of epigenetic therapies seems to be of great importance. The aim of the present paper is the summary of all data on the role of HDACi in DDR, the interference with each DNA repair mechanism and the therapeutic implications of HDACi in MM. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
ER -