Strategy for enhancing the therapeutic efficacy of histone deacetylase inhibitor dacinostat: the novel paradigm to tackle monotonous cancer chemoresistance.
Histone deacetylases (HDACs) regulate gene expression by creating the closed state of chromatin via histone hypoacetylation. Histone acetylation deregulation caused by aberrant expression of classical HDACs leads to imprecise gene regulation culminating in various diseases including cancer. Histone deacetylase inhibitors (HDACi), the small-molecules modulating the biological function of HDACs have shown promising results in inducing cell cycle arrest, differentiation and apoptosis in tumour models. HDACi do not show desired cytotoxic effect when used in monotherapy due to triggering of various resistance mechanisms in cancer cells emphasizing the desperate need of novel strategies that can be used to overcome such challenges. The present article provides intricate details about the novel HDACi dacinostat (LAQ-824) against multiple myeloma and acute myeloid leukaemia. The distinct molecular mechanisms modulated by dacinostat in exerting cytotoxic effect against the defined malignancies have also been detailed. The article also explains the strategy that can be used to circumvent the conventional therapy resistant cases and for enhancing the therapeutic efficacy of dacinostat for effective anticancer therapy.
Plant Virology and Molecular Pathology Laboratory, Division of Plant Pathology, Sher-e-Kashmir University of Agricultural Sciences and Technology of Kashmir, Shalimar, Srinagar, 190025, India. shabir.muntazir82@gmail.com.
Shabir Ahmad
SA
Ganai
Acute myeloid leukaemia; Dacinostat; Histone deacetylase inhibitors; Histone deacetylases; Multiple myeloma