Funded by the Little Princess Trust in partnership with CCLG
Lead investigator: Dr Roisin Kelly-Laubscher, University College Cork
Award: £52,097.00
Awarded July 2023
Because there are more cancer survivors and they are now living longer, the long-term detrimental effects of the drugs used to treat cancer, particularly doxorubicin, are being seen more frequently. When no alternative treatment is available, the choice is between treating with doxorubicin which might damage the heart, or no drug at all. Considering that treating with no drug likely means death, doctors are forced to choose the drug. However, a potential solution would be giving a second drug at the same time as doxorubicin, which would protect the heart. Only one such drug, dexrazoxane, has been approved for this purpose. However, there is mixed evidence about its use in children. Therefore, there is still a need for drugs that can minimise the heart damaging effects of doxorubicin.
Dr Roisin Kelly-Laubscher at University College Cork plans to find out whether another drug, called ethanolamine, could protect the heart if given before doxorubicin treatment. Her lab has evidence that this drug can decrease damage caused by doxorubicin one type of heart cell in the lab, called fibroblasts. However, whilst fibroblasts are very important in the heart, another type of cell, called cardiomyocytes, are the cells responsible for the heart’s contraction. This makes them the most important to protect.
In this project, Dr Kelly-Laubscher will assess the effects of ethanolamine on cardiomyocyte heart cells. There is also the chance that ethanolamine may indirectly protect the cardiomyocytes by protecting the fibroblasts. Therefore, she will also treat cardiomyocytes with the leftover liquid which the ethanolamine-treated fibroblasts were grown in. This liquid will contain any proteins or molecules released by the fibroblast cells, and these could protect the cardiomyocytes.
Once the team has identified a dose of ethanolamine that can protect cardiomyocytes (either directly or indirectly), they will run experiments to find out how best to treat the cells for optimal protection. They will look at how long to give the drug for and when to give it to give cells the best protection (i.e. just before doxorubicin treatment, during doxorubicin treatment and so on). The researchers will use this data to inform further experiments in model systems.
Heart damage caused by doxorubicin can be seen either during treatments (acute) or months and years later (chronic). Whilst the acute form is usually reversible if treatment is stopped, this may mean that the patient is deprived of the best treatment for their cancer. Chronic damage caused by doxorubicin is not reversible and can lead to heart failure. Therefore, an important part of this project is looking at the effects of ethanolamine in model systems treated with doxorubicin dosing strategies that lead to acute and chronic damage to the heart.
If successful, Dr Kelly-Laubscher hopes to use data from this project to apply for further research that would bring this important treatment one step closer to clinical trials.