Recent Scholar Graduates in Focus
Today we’re featuring PhD students funded by the Irish Cancer Society who submitted their PhD thesis and/or passed their Viva in recent months. Through their great work and enormous efforts, each has made an important contribution to cancer research.
Elspeth Ward
From Dublin, Elspeth graduated from UCD in 2013 and soon after began her four-year PhD programme studying breast cancer in RCSI in Dublin. More than 3000 woman in Ireland are diagnosed with breast cancer each year.
Due to improvements in treatment strategies and early detection, breast cancer survival rates are consistently improving. However, many patients do not respond or become resistant to their treatments after initial response. The progression of breast cancer to a resistant state is attributed to genetic and epigenetic alterations. Elspeth’s research focussed on these epigenetic alterations, specifically DNA methylation controlled by a breast cancer protein, SRC-1.
Within this study a novel mechanism utilised by breast tumour cells was discovered which allow these resistant cells to alter the aggressive capacity of the tumour. Fortunately, DNA methylation is a readily reversible event leaving the possibility for treatment-driven reversal of this aggressive event. This work is in review in clinical cancer research currently.
Federico Lucantoni
BREAST-PREDICT PhD student Federico’s research in RCSI in Dublin focussed on using mathematics to predict responses of patient-derived breast cancer cells to chemotherapy. Using this formula, he found that he could precisely predict the extent of cell death in triple negative breast cancer cells
Additionally, Federico and his colleagues established that they can use this formula to identify whether breast cancer cells respond to a new class of agents that enhance the response of cancer cells to chemotherapy. These new types of agents are called BCL2 inhibitors, and represent a new class of drugs already approved for the therapy of specific types of leukaemia.
Standard chemotherapy is the treatment of choice for triple negative breast cancer (TNBC). But it is only effective in a small portion of the patients. At the moment, no targeted therapies are available for TNBC. The tool the research team has developed may predict if a patient will respond to standard chemotherapy. This could potentially help clinicians in deciding the optimal treatment for this type of cancer, and to spare patients who will likely not respond from the toxic effects of unwanted chemotherapy.
Additionally, this study opens the possibility to use BCL2 inhibitors in combination with chemotherapy, for TNBC. It shows that BCL2 inhibitors can restore the tumour’s ability to engage cell death when chemotherapy is applied. This has the potential to improve the effectiveness of chemotherapy in non-responding patients.
Under the supervision of Professor Jochen Prehn, Federico and his colleagues are currently working on testing their models further in more advanced breast cancer models. This will help improve the model and understand how this will perform in a clinical setting. The final aim is to make personalised medicine tools a reality for oncologists and cancer patients.
Federico recently had his work published in the ‘Nature’ scientific journal ‘Cell Death and Disease’.
Killian O’Brien
From Bishopstown, Co Cork, Killian studied biochemtry in UCC before beginning his BREAST-PREDICT PhD under the supervision of supervision of Dr Róisín Dwyer in NUI Galway. The work of Killian and his research team recently received national attention when it was highlighted on RTE News after they recently published a paper in the journal Oncogene.
Dr Dwyer explains this research:
“There have been great advances in detection and treatment of breast cancer, but patients in whom the disease has spread to other organs still have a poor outcome. New treatments for advanced disease are urgently required. microRNAs are short sequences that play an important role controlling expression of genes involved in cancer.
“In a diseased cell, microRNAs that suppress cancer are often lost. We identified one such microRNA, miR-379, and demonstrated that it plays an important role in controlling breast cancer growth. Based on this, we wanted to develop a way to replace lost miR-379 in cancer cells, with a view to treating the disease.
“When cancer has spread it is difficult to deliver therapy to many sites of disease while protecting healthy tissue. However, adult Mesenchymal Stem Cells (MSCs) have the natural ability to home to the sites of tumours. We engineered MSCs to express high levels of the therapeutic microRNA, miR-379, and used them as vehicles to deliver it to the tumour site.
“The MSCs were found to release the microRNA in tiny vesicles. We then isolated the vesicles to determine if they could be used to treat the cancer, without the cells. This could reduce potential side effects. The released vesicles, enriched with miR-379 were shown to reduce breast cancer growth in models of disease. This exciting data preliminary suggests that MSC-secreted vesicles may home to sites of disease and could represent a novel, safe and effective way to treat breast cancer when it has spread to other organs.”
Killian’s PhD was funded through BREAST-PREDICT. You can read an abstract of Killian’s paper here or watch the RTE News report featuring Dr Dwyer here.
