Role of scaffold proteins in the heterogeneity of glioblastoma

Cell Commun Signal. 2024 Oct 7;22(1):477. doi: 10.1186/s12964-024-01809-1.

Abstract

Glioblastoma (GB) is a highly heterogeneous type of incurable brain cancer with a low survival rate. Intensive ongoing research has identified several potential targets; however, GB is marred by the activation of multiple pathways, and thus common targets are highly sought. The signal regulatory scaffold IQGAP1 is an oncoprotein implicated in GB. IQGAP1 nucleates a myriad of pathways in a contextual manner and modulates many of the targets altered in GB like MAPK, NF-κB, and mTOR/PI3K/Akt1, thus positioning it as a plausible common therapeutic target. Here, we review the targets that are subjects of GB treatment clinical trials and the commonly used animal models that facilitate target identification. We propose a model in which the dysfunction of various IQGAP1 pathways can explain to a larger extent some of the GB heterogeneity and offer a platform for personalized medicine.

Keywords: Glioblastoma; IQGAP1; Precision medicine; Scaffold proteins.

Publication types

  • Review

MeSH terms

  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / pathology
  • Glioblastoma* / genetics
  • Glioblastoma* / metabolism
  • Glioblastoma* / pathology
  • Humans
  • Signal Transduction
  • ras GTPase-Activating Proteins / genetics
  • ras GTPase-Activating Proteins / metabolism

Substances

  • ras GTPase-Activating Proteins
  • IQ motif containing GTPase activating protein 1