Title:Panobinostat: The Small Molecule Metalloenzyme Inhibitor with Marvelous Anticancer Activity
VOLUME: 16 ISSUE: 4
Author(s):Shabir Ahmad Ganai
Affiliation:Centre for Nanotechnology & Advanced Biomaterials (CeNTAB), School of Chemical & Biotechnology, SASTRA University, Thanjavur, Tamil Nadu, India.
Keywords:Cancer, Histone deacetylases, Histone deacetylase inhibitors, Metalloenzymes, Multiple myeloma, Panobinostat.
Abstract:Histone acetyl transferases (HATs) and histone deacetylases (HDACs) are antagonistic enzymes
regulating the turnover of histone acetylation thereby governing gene expression in a precise
manner. Histone acetylation deregulation caused by aberrant expression of classical HDACs plays a
crucial role in tumour onset and progression making these enzymes as striking targets for anticancer
drugs and therapy. Small molecule inhibitors targetting HDACs (HDACi) have shown multiple biological
effects including cell cycle arrest, differentiation and apoptosis in cancer cell models. The current
review deals with the recently approved pan-HDAC inhibitor panobinostat (LBH589) and its antiproliferative
activity against distinct cancers (breast, ovarian, lung and multiple myeloma). The intricate details about the
different mechanisms triggered by panobinostat to exert cytotoxic effect in these cancers have also been provided. The article
also highlights the different combination strategies of panobinostat which can be utilized for overcoming conventional
therapy resistant cases and for achieving the enhanced therapeutic benefit from this marvelous inhibitor in the upcoming
future.
