BioCentury
ARTICLE | Distillery Therapeutics

Cancer

December 13, 2016 8:01 PM UTC

Patient sample, cell culture and mouse studies suggest HDAC inhibitors could help treat patients with B cell precursor ALL expressing gene fusions involving MEF2D. Levels of HDAC9 in leukemic cells from bone marrow were higher and survival was poorer in B cell precursor ALL patients harboring MEF2D chromosomal rearrangements than in patients without MEF2D chromosomal rearrangements. In primary bone marrow and spleen cells from four xenograft mouse models of B cell precursor ALL harboring MEF2D-BCL9 gene fusions, the HDAC inhibitor Farydak panobinostat inhibited growth with IC50 values of 0.005-13.4 µM. In primary bone marrow and spleen cells from another four xenograft mouse models of B cell precursor ALL harboring MEF2D-BCL9 gene fusions, the HDAC inhibitor Zolinza vorinostat inhibited growth with IC50 values of 60-930 nM. Next steps include testing HDAC inhibitors in animal models of B cell precursor ALL harboring MEF2D gene fusions.

Merck & Co. Inc. and Taiho Pharmaceutical Co. Ltd. market Zolinza to treat cutaneous T cell lymphoma (CTCL) and have the compound in Phase III testing to treat mesothelioma, Phase I/II testing to treat graft-versus-host disease (GvHD) and Phase I testing to treat brain cancer...