There are many clinically successful anti-cancer agents that target pathways involved in cancer initiation and development. However, FDA has estimated that the elimination rate for investigational new drugs entering clinical trials is up to 80%. One feasible approach to raise the success drug discovery in clinical trials is using predictive biomarkers to evaluate the response of tumors to certain drugs.
Histone deactylase (HDAC), one kind of znic dependent proteases, can remove the acetyl moieties from histones, leading to the reaction between histones and DNA, while blocking the access of transcriptional machinery to the DNA template. Alteration of HDACs has been found in both hematological and solid tumors, which makes it a good anti-cancer target.
So far, three drugs targeting HDAC have been approved and more than 20 are in clinical studies, among which vorinostat (SAHA) was the first approved HDAC inhibitor for clinical treatment of T cell lymphoma by FDA in 2006, romidepsin (FK228) for CTCL in 2009 and resminostat for Hodgkin’s Lymphoma in 2011. Biomarkers elucidating the effect and mechanism of HDAC inhibitors in clinical trials mainly include histone acetylation, induction of p21 and Hsp90, HDAC enzyme activity, gene signatures, HDAC enzymes expression, predictive biomarkers HR23B, tolerances to oxidative stress, and the level of phosphocholine. However, there is still a question that the correlation between the therapeutic response and the biomarkers or any other target proteins was not found precisely.