Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn

PhD: Dr Brona Murphy - Improving Treatment Options for Glioblastoma Patients

The aim of this PhD is to investigate the therapeutic efficacy of CDK inhibitors for GBM patients.

Project description

Glioblastoma (GBM) is the most aggressive form of primary brain tumour, with dismal patient outcome. The reasons for treatment failure are multi-facetted including, the tumour’s extreme resistance to apoptotic death which the treatment strategies of radiation and chemotherapy attempt to induce, the challenge of successfully delivering drugs across the blood brain barrier and the extensive molecular heterogeneity found between tumours.

My group aims to address these complex issues by assessing novel treatment options, employing both in vitro and in vivo models of this disease.

The aim of this study is to investigate the therapeutic efficacy of cyclin-dependent-kinase (CDK) inhibitors for GBM patients. There has been a great deal of interest in the utilisation of these inhibitors as a means to induce apoptosis in treatment-resistant cancer cells.

My group has previously demonstrated that R-roscovitine, a first generation CDK inhibitor re-establishes apoptotic sensitivity in GBM. Newer, second generation CDK inhibitors have the potential to be greater therapeutic candidates due to their significantly improved potency and metabolic stability. This project will specifically utilise patient-derived cells to thoroughly assess the preclinical efficacy of these second generation CDK inhibitors for GBM patients, both on their own and as part of combinatorial approaches.

  • Research theme: Cancer
  • Keyword: Glioblastoma, CDK inhibitors, patient samples

Á. C. Murphy, B. Weyhenmeyer, J. Noonan, S. M. Kilbride, S. Schimansky, K P Loh, D. Kögel, A. G. Letai, J. H. M. Prehn, B. M. Murphy (2014). Modulation of Mcl-1 sensitizes glioblastoma to TRAIL-induced apoptosis. Apoptosis Apr;19(4):629-42. PMID: 24213561

Application process

Interested candidates please email Dr Brona Murphy .

Mentors Dr Brona Murphy