‘Another weapon in the arsenal’: Creating drug hybrids for treating cancer

30 Nov 2021

Sheila Fitzgerald. Image: SSPC

SSPC researcher Sheila Fitzgerald discusses giving additional functionalities to medicines and how the ‘misplaced fear of new drugs’ coming to market can be tackled with science communication.

While studying biopharmaceutical chemistry at NUI Galway, Sheila Fitzgerald got first-hand experience in the industry by undertaking a placement in Bristol Myers Squibb – and decided that this was the career path for her.

She went on to work as a quality control chemist for Regeneron in Limerick, gaining an insight into the complexity of scaling up production of medicines to meet clinical demand, before beginning her PhD studies.

Now, Fitzgerald is a PhD researcher with SSPC, the Science Foundation Ireland research centre for pharmaceuticals, based at the Royal College of Surgeons in Ireland. In the O’Shea Lab, she is working on creating drug hybrids using continuous flow chemistry.

‘I hope that the drug hybrids I create might someday be selected for use in a clinical setting, improving surgical outcomes for cancer patients’

What inspired you to become a researcher?

Both of my parents have backgrounds in science and have always encouraged my curiosity about STEM subjects in school.

My degree course in NUI Galway really gave me a sense of the variety in the sector. During my degree I spent some time in industry and the continual demand for new and innovative medicines fascinated me. I knew this was an area that I really wanted to contribute to and try to make a difference.

Tell us about the research you’re currently working on.

My research focuses on generating drug hybrids. This is essentially taking existing medicines and giving them an additional functionality. By using different chemistries, I can attach an imaging agent to these compounds and then they can function as both a therapeutic drug and a diagnostic imaging agent.

The advantage of this is that a cancer drug that acts on specific cancer cells can be tagged with an imaging agent so that it can also be used to find and image these cells in people. When we do this on a cellular level under a microscope, we can gain a greater insight into how these treatments work and interact with cancer cells.

Furthermore, in an operating theatre it means tumours can be made light up during surgery, distinguishing the tumour edge from healthy tissue giving real-time guidance to the surgical team. It is this combination of drug therapy with improved surgical outcomes that we hope will be of patient benefit.

I undertake the key chemistry step of linking the drug and imaging agent in a glass flow reactor, where the reactions take place while flowing through narrow channels that are not much wider than a few strands of hair. This gives me greater control over the reactions in terms of mixing and heat transfer with attractive safety and environmental benefits.

In your opinion, why is your research important?

For cancer patients undergoing tumour resection, the goal is to achieve tumour-free surgical margins. If any cancerous cells are remaining it can unfortunately result in tumour reoccurrence.

Fluorescence image-guided surgery can give a surgeon another weapon in their arsenal when undertaking these procedures. I hope that the drug hybrids I create might someday be selected for use in a clinical setting, improving surgical outcomes for cancer patients.

What commercial applications do you foresee for your research?

The beauty of continuous flow chemistry is how readily transferrable it is from research lab scale to an industrial setting. A major advantage in flow is the ease that it can be scaled up in contrast with traditional batch scale-up. It is achieved by continually running the process for longer time periods, known as ‘scaling out’.

My work focuses on real-time reaction monitoring and ease of purification, or eliminating it altogether. Purification is quite possibly the number-one cause of heartbreak for a synthetic chemist, so being able to scale up and eliminate it is very desirable.

What are some of the biggest challenges you face as a researcher in your field?

I think every PhD student has a fear in the beginning of their research career about not knowing enough and being terrified of failure. You quickly start to realise you are discovering new things, creating new knowledge and that any failures you might encounter are just signposts for redirection.

Research is very collaborative and our group meets regularly to brainstorm any roadblocks we’re experiencing.

Are there any common misconceptions about this area of research?

There is often a lot of misplaced fear of new drugs coming to market and unknown side effects. I’ve seen it a lot of late with the vaccine roll-out.

Every drug that becomes commercially available undergoes an extremely rigorous validation process beforehand. Post-approval, the production of these medicines is continually under review from a number of health authorities or agencies ensuring the highest level of quality and safety is achieved.

The best way to alleviate these fears is through effective science communication. The science behind these technologies can be daunting if it’s not accessible.

What are some of the areas of research you’d like to see tackled in the years ahead?

As a flow chemist, I would love to see continuous flow synthesis become common place in industrial settings. Climate change and global warming are at the forefront of people’s minds and moves towards sustainable change are more important than ever.

Flow synthesis is performed at high concentration with minimal solvent consumption, which yields huge environmental and economic benefits. This is advantageous for planet and patient in making medicines more affordably produced.

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