Trinity researchers have made a groundbreaking discovery that could fight resistance to radiotherapy in cases of oesophageal cancer.
The new discovery made by Dr Stephen Maher, Ussher Assistant Professor of Translational Oncology, and his team, which includes scientists from Trinity, St James’s Hospital, the Coombe Women and Infants University Hospital and the University of Hull, could help to overcome a major obstacle to treatment of oesophageal cancer. Their research, which was published in the scientific journal Oncotarget, has revealed that the loss of a powerful gene-regulating molecule called miR-17 from cancer stem cells plays an important role in driving oesophageal tumour resistance to radiotherapy.
Currently resistance to radiotherapy is a major problem with oesophageal cancer, with the majority of patients having some resistance, causing delays in surgery. The research, largely funded by the Health Research Board (HRB), demonstrated that populations of tumour cells that had higher numbers of cancer stem cells formed larger, more aggressive tumours. They demonstrated that the cancer stem cells were more resistant to radiation-induced cell death. The research also showed that that the population of cancer stem cells could be further broken down into smaller groups, which had distinct radiation sensitivity profiles.
Further genetic analysis revealed that the levels of miR-17 were particularly low in the cancer stem cells that were most resistant to radiation. In patient samples, miR-17 was found to be much lower in the tumours of patients who did not respond to treatment. The work also made the key discovery that by placing a synthetic version of miR-17 into the resistant cells, they became more sensitive to radiation which the team believe could be used to enhance the effectiveness of radiotherapy treatment in the future.
Dr Maher described the research as “extremely important in understanding why tumours are inherently resistant to radiotherapy, and how they can acquire resistance”.
Oesophageal cancer is a major problem in Ireland and the rest of the western world. Cases of this type of cancer have increased by 600% over the past three decades, making it the largest increase in incidence of any disease of any kind over the same time period. Rates are expected to continue increasing over the next 20 years.
