In many clinical trial settings, repeated access to the primary target tissue of interest is difficult or impossible. In these cases, sampling of a surrogate tissue is essential to understand engagement of test compounds or agents, for example by measuring dose dependent transcriptional regulation of specific genes or pathways.
Plucked scalp anagen hair represents an ideal surrogate tissue, particularly in oncology. Anagen hair's epithelial composition, rapidly proliferating cells and high degree of vascularisation make it biologically relevant given that 80-90% of solid tumours are epithelial in origin. In addition, its non-invasive nature means patients are more likely to consent to providing samples.
A recent paper by Tanis et al 2016, examined the transcriptional response to gamma-secretase inhibition of Notch pathway signalling in human and non-human primate hair follicles and blood and supports the utility of plucked hair as a peripheral surrogate biomarker tissue. Plucked hair and blood transcriptomes were analysed in healthy human volunteers following oral dosing with a gamma-secretase inhibitor (GSI).
Of a pre-determined signature of 11 target genes in the Notch pathway investigated for pharmacodynamic response to GSI treatment, only one gene in blood showed modulation, whilst 5 genes in hair exhibited a pharmacodynamic response to GSI treatment.
An improved gene expression biomarker signature was developed from genome-wide analysis in anagen hair that indicated engagement with the Notch signaling pathway and exhibited an excellent PK/PD relationship. Such correlations could not be established in peripheral blood.