[Little Monkey]

New study about response to vorinostat (Zolinza)

by Little Monkey on Sat Mar 10, 2018 8:45 am

Here is a study I came across about the use of vorinostat (Zolinza) as a combination therapy in treatment for some types of myeloma.

Bruyer, A, et al, "DNMTi/HDACi combined epigenetic targeted treatment induces reprogramming of myeloma cells in the direction of normal plasma cells," British Journal of Cancer, March 2, 2018 (full text of article)

Abstract:

Background - Multiple myeloma is the second most common hematologic malignancy. Aberrant epigenetic modifications have been reported in multiple myeloma and could be promising therapeutic targets. As response rates are overall limited but deep responses occur, it is important to identify those patients who could indeed benefit from epigenetic-targeted therapy.

Methods - Since HDACi and DNMTi combination have potential therapeutic value in multiple myeloma, we aimed to build a GEP-based score that could be useful to design future epigenetic-targeted combination trials. In addition, we investigated the changes in GEP upon HDACi/DNMTi treatment.

Results - We report a new gene expression-based score to predict multiple myeloma cell sensitivity to the combination of DNMTi/HDACi. A high Combo score in multiple myeloma patients identified a group with a worse overall survival but a higher sensitivity of their multiple myeloma cells to DNMTi/HDACi therapy compared to a low Combo score. In addition, treatment with DNMTi/HDACi downregulated IRF4 and MYC expression and appeared to induce a mature BMPC plasma cell gene expression profile in myeloma cell lines.

Conclusion - In conclusion, we developed a score for the prediction of primary multiple myeloma cell sensitivity to DNMTi/HDACi and found that this combination could be beneficial in high-risk patients by targeting proliferation and inducing maturation.