There is still a great deal we don’t know about FA, and while research to date has helped extend the lives of many people born with FA, our hope is that we can find more effective treatments of FA cancers. Fanconi Hope is currently supporting research being done by biomedical scientist Joseph Hallett, a 4th year PhD student at The University of Manchester. A typical day counting colonies!
We chatted with Joseph to find out what he’s working on and how it might change the lives of people with FA.
So what is your research all about?
My project aims to understand the effects of proton beam vs conventional radiation/x-rays on Fanconi cells. We want to understand how protons and conventional x-rays compare in non-cancerous as well as cancerous cells to understand the toxicity and efficacy of both forms of radiotherapy.
Why is this important for people born with FA?
People will FA often develop head and neck cancers in their late twenties and early thirties. While in non-Fanconi patients, these cases may be dealt with using chemo and radiotherapy, in FA patients, because they have a DNA repair defect, these DNA damaging treatments are generally not offered. However, the evidence against their use in FA is by no means concrete.
Furthermore, proton beam therapy, a type of radiotherapy using protons, is much more precise, meaning that less normal tissue is affected, and the tumor can be targeted. This is because the particles that make up the radiation are much bigger, and they deliver their energy differently. We know that most energy is delivered just before they stop, so we can calculate their trajectory to make them hit the tumor at that moment, reducing damage to non-cancerous cells.
How do you go about researching something like that?
There are many experiments in which flasks containing a single layer of FA or non-FA cells are exposed to either protons or x-rays. We can then compare the cellular response using many different types of assays, which typically examine cell survival and DNA damage. For example, colony forming assays are the assay of choice for assessing the radiosensitivity of cell lines. Here we expose the different cells to radiation and then measure how many of the single cells survive, by counting how many were able to grow into large colonies/groups of fifty cells or more after 2 weeks. This all helps us to understand how cancerous and non-cancerous cells from FA patients tolerate each form of radiation and whether they are more radiosensitive than non-FA cells.
What have you found out so far?
We have seen that the non-cancerous cells react in the same way to each radiation type whether they are Fanconi or not. Whereas the Fanconi cancerous cells seem to be more radio-sensitive than normal cancerous cells. Furthermore, we also see that conventional radiation is a little more radio-lethal than protons in the cancer cells. This is interesting and may mean that we can reduce the radiation dose for FA cancer patients and only offer protons in select clinical cases.
What’s next for you?
I’m in year four of four in my PhD so I’m currently finishing the final large-scale experiments, which look in detail at how and why thousands of proteins within the cells change in response to the two types of radiation, in cancer and non-cancer cells, with and without FA. As you can imagine this is producing a lot of complex, but highly informative data. I am presenting this work at this year’s FCF (Fanconi Cancer Foundation) symposium in Charlotte North Carolina in September! Afterwards I will write up my PhD thesis and publish my data in the form of a paper in a leading journal, so that it can be taken to the next level.
What will happen next to your research?
The next stage might be to do some animal work, for example looking at how Fanconi mice react to each radiation type. Equally, once my results have been shared in a journal, it might be taken forward into a clinical trial, or lead to a change in clinical practice. My expertise is the cell biology, so it would be up to clinicians, but my hope is that my data can be used to one day inform clinical practice and extend the lives of people living with FA today.
Joseph’s PhD programme is fully funded by Fanconi Hope
If you’d like to be interviewed for our next newsletter, please contact katie@fanconihope.org