The safety of a new generation epigenetic drug has been proven
Epigenetics is a research field that studies changes in gene expression and, accordingly, variations in the cellular phenotype caused by mechanisms other than changes in the sequence of nucleotides in DNA. These mechanisms consist in changing the activity of synthesis of the corresponding proteins due to their modification (cleavage or attachment to DNA of various chemical groupings) and play a huge role in many natural processes – for example, they provide the ability of a caterpillar to turn into a butterfly without changing DNA.
The target of the drug, developed by British scientists from the Institute of Cancer Research and the company Chroma Therapeutics, working under the guidance of Dr. Udai Banerji, is the enzyme histone deacetylase, which controls the expression of genes by activating or inactivating them by modifying histones – proteins that ensure the ordering and packaging of DNA chains. Errors in the work of this enzyme can lead to the development of cancer due to a violation of the normal process of decoding information encoded in DNA.
In the field of clinical epigenetics, to date, the greatest success has been achieved in the development of histone deacetylase inhibitors. Two drugs of this group have already been approved for use for the treatment of a certain type of lymphoma, but their use is limited by serious side effects, as well as the need for injecting one of them.
The new generation inhibitor CHR-3996 selectively suppresses the activity of one of the variants of this enzyme – histone deacetylase class I. The developers hope that this will avoid side effects caused by existing drugs without reducing the severity of the antitumor effect. When conducting experiments in the laboratory, they demonstrated the ability of CHR-3996 to destroy cells of various types of cancer.
The drug has also been successfully tested for safety in the framework of phase I clinical trial. The results obtained demonstrated its activity when taken in tablet form, as well as the absence of serious side effects. Moreover, one of the patients had a decrease in the size of the pancreatic tumor, while the condition of the remaining 9 patients remained stable for at least two months. According to the results of blood tests, the drug affected its target, while its concentration in the body corresponded to the concentration sufficient to destroy the tumor in the preclinical model.
Experts believe that an epigenetic approach to therapy, the purpose of which is to influence the chemical "switches" of gene activity, and not directly on DNA, is a very promising direction for the development of new drugs.
Article by Udai Banerji et al. A Phase I Pharmacokinetic and Pharmacodynamic Study of CHR-3996, an Oral Class I Selective Histone Deacetylase Inhibitor in Refractory Solid Tumors is published in the journal Clinical Cancer Research.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of Clinical Cancer Research:
Epigenetic Cancer Pills Are Safe.
03.05.2012