Abstract 1867: Gene expression profiles obtained from ex vivo human scalp hair to determine the effects of drug response following exposure to HDAC inhibitors

Background Plucked human scalp hair represents an ideal surrogate tissue to enable non-invasive monitoring of drug response in clinical trials. Congruence of patterns of transcriptome activity within the bulb region of plucked scalp hair show high concordance and to that of primary target tumour tissues. The ex vivo plucked scalp hair culture technique involves exposing healthy normal volunteer hair to different concentrations of a number of HDAC inhibitors and ascertain the effects that they have on gene expression. This technique is an ideal approach to identifying desirable non-invasive transcriptional biomarkers to demonstrate target engagement and define a PK/PD relationship, as well as enabling the monitoring of a well tolerated dose schedule with maximal biological effect. Materials and Methods In this study, we deployed our proprietary ex vivo culture technique to ascertain the effects that three different HDAC inhibitors had on gene expression in plucked hair. Three different concentrations of each HDAC inhibitor were incubated in culture for a period of 18 hours. RNA was extracted from the hair bulb following the culture technique and gene expression was assessed following microarray analysis. Statistically significant biomarkers (p