Intratumor MAPK and PI3K signaling pathway heterogeneity in glioblastoma tissue correlates with CREB signaling and distinct target gene signatures
PM Daniel, G Filiz, MJ Tymms, RG Ramsay, AH Kaye, SS Stylli, T Mantamadiotis
Experimental and Molecular Pathology | Elsevier | Published : 2018
Limitations in discovering useful tumor biomarkers and drug targets is not only due to patient-to-patient differences but also due to intratumor heterogeneity. Heterogeneity arises due to the genetic and epigenetic variation of tumor cells in response to microenvironmental interactions and cytotoxic therapy. We explored specific signaling pathway activation in glioblastoma (GBM) by investigating the intratumor activation of the MAPK and PI3K pathways. We present data demonstrating a striking preponderance for mutual exclusivity of MAPK and PI3K activation in GBM tissue, where MAPK activation correlates with proliferation and transcription factor CREB activation and PI3K activation correlates..View full abstract
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Awarded by CASS Foundation Grant
Parts of this work were funded by a CASS Foundation Grant (7941) and Brain Foundation Award (Brain Tumours Award 2017)- Better drugs for Brain Cancer.