Journal article

Intratumoral MAPK and PI3K signaling pathway heterogeneity in glioblastoma tissue correlates with selective CREB signaling and specific functional gene signatures

Paul Daniel, Gulay Filiz, Martin Tymms, Robert Ramsay, Andrew Henry Kaye, Stanley Stylli, Theo Mantamadiotis

Experimental and Molecular Pathology | Elsevier | Published : 2018

Abstract

Limitations in discovering useful tumor biomarkers and drug targets is not only due to patient-to-patient differences but also due to intratumoral 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 intratumoral 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 correl..

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