Interview with Gareth Veal

Gareth Veal

Newcastle University

Newcastle upon Tyne, UK

It was a real pleasure to meet Gareth Veal at last years’ congress and to hear about the national TDM programme to support paediatric oncology patients in the UK. The programme was awarded an important grant last year, reflecting the excellent work done by this research group to develop a service that is solicited and highly valued by clinicians nationwide. Gareth shares about the programme, some innovative approaches the group is developing, novel technologies to keep an eye on and his vision for the future of TDM.

Can you tell us a little bit about your respective roles? What is a typical day like for you?

I have worked in academia my whole career and one of the things that I really like is that a ‘typical day’ can vary week to week or month to month. I predominantly carry out research and enjoy spending time planning new studies, analysing data from ongoing studies, writing grants to bring in funding and drafting papers for publication. If I’ve spent weeks working on a grant application to meet a deadline, for example, then it’s great to be able to shift to working on something completely different for a while. I also spend some of my time teaching, whether this is lecturing to undergraduate or Master of Research students, supervising laboratory projects or discussing data with PhD students. The key thing is working with people who are enthusiastic about science and share the same research goals. In this respect I’m lucky to have a great team of scientists who I’m able to work with on a daily basis.

Is there anything that your laboratory does, or that is done at your hospital/center, that you would consider innovative?

The Newcastle Cancer Centre Pharmacology Group has a very translational approach to research and we are regularly tasked with the development of novel assays for the quantification of new drugs ahead of early phase trials and patient sample analysis. In the modern era of cancer research new drugs come in a wide range of shapes and sizes and each new assay will come with its own particular challenges. A recently published assay from our group involved the development of a novel drug penetration assay that allowed us to quantify levels of a PEGylated molecule in multiple levels of tumour material collected from punch biopsy specimens following topical administration. This was then applied in a clinical setting to investigate relative tumour drug exposure in patients participating in an early phase clinical trial of this drug.

What technological innovations have entered into use during your career that have permitted a change, or evolution, in practice?

The advances in mass spectrometry made over the past 20 years have been key to the evolution of clinical pharmacology studies and therapeutic drug monitoring approaches to treatment. LC/MS machines now widely available to researchers allow us to quantify drug levels from minimal volumes of clinical sample with an incredible degree of sensitivity. More recently advances such as the iKnife have the potential to genuinely revolutionise the treatment of cancer patients in terms of providing real-time analysis of tumour tissue in a surgical setting.

How did you become interested in your area of expertise?

I carried out my PhD studies at Liverpool University in the 1990s, a time when research into the treatment of HIV disease was very much at its height. My studies involved establishing assays for the quantification of zidovudine and other nucleoside analogues and their active triphosphate metabolites in peripheral blood lymphocytes collected from patients following treatment. This was my first introduction to HPLC assays and bioanalysis, working in a thriving research environment and I guess I never really looked back from this point on.

Is there anything that you’ve seen or heard about recently and thought “I’d like to incorporate that idea at my center”?

We are very keen to progress our work on the development of assays for the quantification of anticancer drug levels from dry blood spot or related micro blood sampling approaches. The development of such approaches to the point of their appropriate utilisation for clinical sample analysis could have a significant impact on the clinical trials that we are involved in. In particular, current studies involving neonates and very young children are commonly limited by the number of blood samples that it is safe to draw within a defined period of time. Micro blood sampling approaches would not only limit the volume of blood being collected but would also facilitate more intensive sampling strategies, with the potential for collecting samples when the patient is away from the hospital. We also have active collaborations with groups in countries, such as India, where the collection of clinical samples for research studies can be limited by the lack of a cold chain currently required to ensure sample integrity. The successful development of assays to provide sound data from samples collected by dry blood spot or micro blood sampling devices could have a really positive impact on the work that we do and we feel is well worth investing the required time and effort to progress.

What sort of research do you have on the horizon that you think might influence clinical practice in the future?

A major area of interest for my research group focuses on the development of a national Therapeutic Drug Monitoring (TDM) programme of work to assist in the treatment of particularly ‘hard to treat’ childhood cancer patients. Recent studies have focused on learning about the pharmacokinetics of anticancer drugs in preterm infants and neonates, an incredibly challenging patient subpopulation to treat in terms of determining the optimal dosing regimens to utilise. In this space we recently obtained a grant from the Research for Patient Benefit funding stream of the National Institute for Health Research (London, UK) for carrying out TDM approaches in hard to treat childhood cancer patient groups. This 3 year programme of work will allow us to roll out a national programme utilising real-time drug levels to maximize the chances that patient groups (including neonates, anephric and obese patients) achieve drug concentrations that are most likely to result in efficacy with acceptable toxicity profiles.

What do you consider is the future for TDM and CT? What are you excited about? What are the challenges we face?

One of the challenges I see in the future relates to the accessibility of LC–MS and other analytical equipment. We are increasingly identifying drugs and patient populations whereby TDM approaches are being shown to be the most appropriate approach to treatment. Currently our laboratory in Newcastle carry out the analysis of patient samples for centers treating childhood cancer patients across the UK, but as this area progresses it would be ideal for centers to be able to generate data on drug exposures at the point of care. This would realistically require the development of smaller and more cost-effective instruments which can be used more routinely in clinical centers.