The prospect of a single human hair being used as a biomarker source for oncology drug development has moved closer to reality with the successful completion of a feasibility study on technology developed by UK biotech Epistem.

The study was conducted by Epistem, whose research efforts focus on the regulation of adult stem cells found in epithelial tissue, in collaboration with AstraZeneca. Epistem’s proprietary plucked hair biomarker platform is designed as a minimally invasive tool for measuring the effects of new cancer treatments over time. In this way, informed decisions on whether to proceed with investigational compounds can be taken before the drug candidates move into more expensive stages of development.

The procedure involves taking individual plucked hairs at various points during cancer treatment and analysing gene expression changes in RNA extracted from the bulb of cells at the base of each hair. As Epistem points out, hair follicles are highly sensitive to therapeutic agents, including radiation and chemotherapy, with gene changes apparent within hours of exposure or dosing. The changes in gene expression can then be used to identify core gene sets or biomarkers that will help to steer the drug development programme.

The technology has applications in both the preclinical and clinical phases of the development process. In the first case, RNA is extracted from hair follicles during subcutaneous xenografting studies and amplified into cDNA using Epistem’s proprietary technology. Gene expression profiling is then performed on the RNA from excised tumours and hair follicles. Identified gene sets with the potential to predict efficacy, drug exposure and toxicity can be taken forward to Phase I trials.

With the clinical biomarker platform, single hairs are plucked from human subjects before and after treatment in Phase I. RNA is again extracted from the hair follicles and amplified into cDNA. Gene expression profiling is conducted to identify a core gene set with potential to demonstrate drug exposure (the level of drug and length of time required to affect signalling pathways); dose and schedule (the duration of drug effects over dose ranges and time); early indications of toxicity (maximum tolerated dose); and biological activity as a surrogate marker for tumour regression.

In the feasibility study with AstraZeneca, the two companies demonstrated that single plucked hairs sampled over multiple time points provided effective levels of DNA for gene expression measurement. The process was well tolerated by participants, while samples proved to be robust during shipment and storage. More than 85% of the hairs sampled were evaluable for measurement, Epistem said. Further analysis also established reliable detection of more than 13,000 genes in single hairs.

Pathways of interest
Epistem and AstraZeneca plan to explore hair follicle core gene sets based on drug-induced gene expression in pathways of interest for specific therapeutics. Identified gene expression changes in the hair follicle will be linked to changes in tumours to determine drug exposure, toxicity and dose response, hence guiding patient selection.

As Epistem observes, the identification of appropriate biomarkers for drug development gained traction last year with the launch of the Biomarkers Consortium, set up in the US by the Foundation for the National Institutes of Health (FNIH), the National Institutes of Health (NIH), the Food and Drug Administration (FDA) and Pharmaceutical Research and Manufacturers of America (PhRMA). AstraZeneca is an active member of this consortium.

A joint scientific abstract of the hair biomarker feasibility study was recently presented by Epistem and AstraZeneca at the International Conference on Molecular Targets and Cancer Therapeutics held by the American Association for Cancer Research, the US National Cancer Institute and the European Organisation for Research and Treatment of Cancer in San Francisco.