Poster Presentation 27th Lorne Cancer Conference 2015

Reducing Glioblastoma Multiform malignancy through the reactivation of the cAMP/PKA/CREB pathway (#147)

Paul Daniel 1 , Daniel Brown 1 , Gulay Filiz 1 , Theo Mantamadiotis 1
  1. Melbourne Uni, Parkville, Vic, Australia
Glioblastoma Multiforme (GBM) is the most commonly diagnosed and deadly glioma type yet remains uncurable despite the advances in understanding the underlying biology of this disease. Targeted therapies looking to exploit oncogenic pathways involved in malignancy have reached clinical trials however lack of success in effecting outcome highlight the inadequacy of current targets and need for novel approaches. Using the TCGA and Rembrandt databases, we have identified the cAMP/PKA/CREB pathway as a tumour inhibitory pathway which is activated in patients which have better overall survival and prognosis. Reactivation of this pathway selectively induces apoptosis in a subset of GBM cell lines expressing the mesenchymal marker CD44 through CREB mediated transcription of the pro-apoptotic factor BIM.  Furthermore, we have found that activation of cAMP/PKA/CREB enhances the cytotoxic effect of the alkylating agent Temozolomide (TMZ). Finally, we identify a clinically relevant patient population in which reactivation of the cAMP/PKA/CREB pathway may be used as a novel target for the treatment of GBM.