Showing posts with label HDAC_inhibitors. Show all posts
Showing posts with label HDAC_inhibitors. Show all posts

Wednesday, 17 January 2018

Histone deacetylase inhibitors (HDACi)

I find a lot of information that histone deacetylase inhibitors (Trichostatin A (TSA), Vorinostat, 7-ureido-N-hydroxyheptanamide derivative (CKD5)) have potent anti-cancer effects in glioblastoma.

2017 https://www.ncbi.nlm.nih.gov/pubmed/27852054
"Our results demonstrate that the novel HDACI CKD5 is a promising therapeutic candidate for glioblastoma."

2017 https://www.ncbi.nlm.nih.gov/pubmed/27766591
"We conclude that the combined administration of TSA and CCNU eradicates GBM cells with a higher efficacy than either drug alone, thereby opening a novel avenue for the treatment of GBM."

2015 https://www.ncbi.nlm.nih.gov/pubmed/25634603
"...these results indicate that trichostatin A (TSA) suppresses ESCC cell growth by inhibiting the activation of the PI3K/Akt and ERK1/2 pathways. TSA also promotes cell apoptosis through epigenetic regulation of the expression of apoptosis‑related protein."

2014 https://www.ncbi.nlm.nih.gov/pubmed/24464841
"Here, we investigate the effects of the HDACi trichostatin A (TSA) in U87 GBM cultures and tumorsphere-derived cells. These findings indicate that HDACis can inhibit proliferation, survival, and tumorsphere formation, and promote differentiation of U87 GBM cells, providing further evidence for the development of HDACis as potential therapeutics against GBM."

The results of clinical trials, however, did not give a good result:

Phase I/II Trial of Vorinostat Combined with Temozolomide and Radiation Therapy for Newly Diagnosed Glioblastoma: Final Results of Alliance N0874/ABTC 02.
2017 https://www.ncbi.nlm.nih.gov/pubmed/29016887

Phase II Study of Bevacizumab and Vorinostat for Patients with Recurrent World Health Organization Grade 4 Malignant Glioma.
2017 https://www.ncbi.nlm.nih.gov/pubmed/29133513

"Valproic acid has also recently been demonstrated to be a potent histone deacetylase inhibitor."
Many patients with glioblastoma take valproic acid (Depakote) against epileptic attacks. However, this has no effect on overall survival. Perhaps it is necessary to increase the dose or combination with something? I found that disulfiram increases the content of valproic acid in the blood.

And by the way, I can not find any medicine containing Trichostatin A.