Novel epigenetic therapy to treat mantle cell lymphoma

Scientists at Bellvitge Biomedical Research Institute have developed a small molecule epigenetic drug, targeting HDAC6, which could slow down cell growth in mantle cell lymphoma.

Go to the profile of Jasmine Harris
Jun 13, 2018
0
0

A recent study published in Haematologica describes a novel small molecule for the treatment of mantle cell lymphoma (MCL), an aggressive cancer characterized by a typically late diagnosis and originating from the B lymphocytes. The epigenetic drug inhibiting histone deacetylase 6 (HDAC6) could increase long-term survival of the disease.

"Our laboratory is interested in finding new compounds with epigenetic activity and anti-tumor effects. Working together with organic chemists and the Quimatryx company we obtained a molecule that inhibits the HDAC6 gene, a protein that chemically modifies another protein by acetylation," commented lead author of the study, Manel Esteller, Director of the Epigenetics and Cancer Biology Program at the Bellvitge Biomedical Research Institute (Barcelona, Spain).

The team synthesized a potential selective HDAC6 inhibitor, QTX125 [3-(3-furyl)-N-{4-[(hydroxyamino)carbonyl]benzyl}-5-(4-hydroxyphenyl)-1H-pyrrole-2-carboxamide], through a seven step synthesis, which is suitable for kilogram-scale production. In an assay of 48 human cancer cell lines, QTX125 demonstrated the strongest growth-inhibitory effect in Burkitt’s cell lymphoma, follicular lymphoma and MCL.

"After testing it on several types of cancer, we realized that the efficacy of the new molecule was at its peak in this type of lymphoma. This beneficial effect was observed in cultured cells, murine studies and cells extracted from patients. In addition, the substance is very specific when it comes to reaching its target, with apparent little toxicity to healthy cells of the same patient, such as T lymphocytes," added Esteller.

In in vivo mouse models, the drug QTX125 also exhibited anti-tumor properties. The researchers hope the small molecule can be taken forward to clinical trials for the epigenetic treatment of MCL.

 

Sources:
Perez-Salvia M, Aldaba E, Vara Y et al. In vitro and in vivo activity of a new small-molecule inhibitor of HDAC6 in mantle cell lymphoma. Haematologica. doi:10.3324/haematol.2018.189241 (Epub ahead of print) (2018); www.idibell.cat/en/whats-on/noticies/new-epigenetic-drug-against-mantle-cell-lymphoma

Go to the profile of Jasmine Harris

Jasmine Harris

Digital Editor, Future Science Group

No comments yet.