An alliance between two UK companies and the University of Manchester aims to validate the emerging field of serological pharmacodynamic (PD) biomarkers as a less invasive and time-consuming means of tracking drug effects in clinical trials of new cancer therapies.

The two commercial partners are Cancer Research Technology Limited (CRT), the London-based development and commercialisation arm of Cancer Research UK, and AstraZeneca (AZ). The two companies will support a research programme at the University of Manchester investigating biomarkers of tumour cell death using specialist PD assays.

The work will be carried out in the laboratories of the Clinical and Experimental Pharmacology Group at the university’s Paterson Institute of Cancer Research (PICR). AZ’s financial contribution is undisclosed, but it will help pay for five full-time research scientists at the PICR, which is one of four research institutes core-funded by Cancer Research UK. CRT will have exclusive rights to commercialise any novel biomarkers identified in the course of the three-year collaboration.

The agreement builds on a clinical pharmacology biomarker research and discovery collaboration formed between CRT, AZ and the University of Manchester last November. That partnership reinforced existing collaborative links between the two companies and the PICR by setting up two clinical pharmacology research fellowships, jointly funded by Cancer Research UK and AstraZeneca, and geared to identifying and validating circulating biomarkers for use in conjunction with targeted cancer therapies.

As CRT noted, targeted treatments call for robust biomarkers that reflect the molecular pathology of tumours and predict or indicate drug responsiveness. Potential applications include effective determination of optimal biological doses, establishing proof of concept for target modulation, selecting patients most likely to respond to therapy, and detecting subsequent resistance to treatment. “Ultimately, biomarkers help explain or predict clinical outcomes and reduce the costs of drug development,” CRT commented.

Skills deficit

The extended CRT-AZ-PICR collaboration will take this work forward, as well as further addressing the current skills deficit in clinical pharmacology that is compromising the UK’s status in early-stage drug development. Within the alliance, the PICR’s Clinical and Experimental Pharmacology Group, jointly led by Professor Caroline Dive and Dr Malcolm Ranson, will provide “cutting-edge” expertise in PD assay development and implementation, CRT said.

This group specialises in using immunohistochemical, flow cytometric and ELISA (Enzyme-Linked Immunosorbent Assay)-based techniques for progressing and validating biomarkers related to cancer. “These expertises have previously been used to validate biomarkers of angiogenesis and cell death that are now being employed in a clinical trial setting,” CRT pointed out.

Serum biomarkers make it easier in clinical trials to track a new drug and “what it’s doing," commented CRC spokesman Michael Regnier. At the moment, researchers rely on tumour biopsies, which are invasive and take time. Serological PD biomarkers are a developing field but the tools need validating before they can be applied to drug development, Regnier said.

“Tumour cell death is the final event which we seek for many of our molecularly targeted agents,” stated Professor Andrew Evans, AZ’s clinical director of discovery medicine. “If we can measure this event in a blood sample rather than from a tumour biopsy – the current gold standard – it minimises the intervention for the patient and maximises the opportunity of detecting what is likely to be a dynamic event by allowing for repeat sampling.”