MCT Research Talks – 5th December 2016
Cancer Genetics Group
Neuroblastoma is a childhood cancer caused by the abnormal growth and development of neural crest cells (1). The disease commonly affects children age 5 years or younger. Approximately 50% of children have cancer cells that have migrated to distant sites in the body and formed tumour masses at the time of diagnosis. The main challenge in treating neuroblastoma is to combat tumour metastasis and development of resistance to multiple chemotherapeutic drugs. Despite major advances in available therapies, children with drug resistant and/or recurrent neuroblastoma have a dismal outlook with 5 year survival rates of less than 20%.
Research of Prof. Stallings lab is focused on elucidating the molecular events that contribute to the development and progression of neuroblastoma (2). A major area of research involves the identification and functional analysis of microRNAs that contribute to chemotherapy resistance in neuroblastoma, along with the development of microRNA-mediated therapeutics.
The main research projects were presented at the Departmental meeting on December, 5th.
The first talk by Olga Piskareva has explored how current concepts of development of drug resistant, tumour microenvironment and cell-to-cell communication can be applied to reconstruct relapsed or drug resistant neuroblastoma microenvironment using 3D tumour models.
The second talk was presented by Ciara Fallon. Ciara is our StAR PhD student. She has selected the project ‘Exosome mediated drug resistance in high-risk neuroblastoma’ as her first choice. At the moment she is doing her lab placement in Cancer Genetics group as a part of the RCSI StAR PhD Programme. Built upon results of the former BioAt PhD Student Ross Conlon (3), Ciara’s project is focused on the validation of exosomal miR-548d-5p as a regulator of cell viability and proliferation in cisplatin sensitive and resistant neuroblastoma cell lines.
Finally, the last, but not least was a talk by John Nolan. His talk entitled “MiRNA-124-3p Reduces Cell Viability in Cisplatin Resistant Neuroblastoma Cell Models” was focused on the results submitted to the Royal College of Surgeons for the Degree of Doctor of Philosophy. His studies cover the development of cross resistance to other drugs, investigation of common altered proteins and signaling pathways in cisplatin resistant neuroblastoma cell lines and validation of miRNA that can target these proteins and stop cell proliferation. Part of the results was published last year in Cancer Letters (4).
The work carried out in Prof. Stallings lab is supported through the research grant to Prof. Ray Stallings and PhD fellowship to John Nolan by National Children’s Research Centre, Crumlin Hospital.
- Davidoff, A. M. Neuroblastoma. 2012 Semin. Pediatr. Surg. 21, 2–14.
- Piskareva, O., Stallings, R. Neuroblastoma. In: Epigenetic Cancer Therapy edited by Grey S., Elsevier 2015.
- Conlon, R., Analysis of microRNA bearing exosomes in models of drug resistant neuroblastoma. PhD Thesis. Dublin: Royal College of Surgeons in Ireland; 2015.
- Piskareva, O., Harvey, H., Nolan, J., Conlon, R., Alcock. L., Buckley, P., Dowling, P., O’Sullivan, F., Bray, I., Stallings, T.L. The development of cisplatin resistance in neuroblastoma is accompanied by epithelial to mesenchymal transition in vitro. 2015 Cancer Letters, 364:142-55.
Reported by Olga Piskareva