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. Author manuscript; available in PMC: 2024 Jun 1.
Published in final edited form as: Nat Rev Neurosci. 2023 Oct 19;24(12):733–746. doi: 10.1038/s41583-023-00744-3

Table 1 |.

Glioma cell state heterogeneity drives distinct mechanisms of network communication which informs potential therapeutic strategies

Glioma type Cell state resemblance Network interactions Molecular mechanisms and therapeutic targets Clinically available drugs that impact glioma preclinical models
Paediatric low-grade OPC, astrocyte161 Paracrineb, neuronal hyperexcitabilityb NLGN3b, HCNb ADAM10 inhibitorsb, lamotrigineb
IDH and H3 wild-type high-grade glioma OPC, astrocyte, MES, NPC87 Neuron–glioma synapse, tumour microtube, neuronal hyperexcitability, paracrine, hub cells (also called pacemaker or oscillatory cells) AMPAR, potassium channels, CX43, NLGN3, KCa, TSP1, IGF1 Perampanel, meclofenamate, senicapoc, gabapentin, ADAM10 inhibitors
IDH-mutant astrocytoma NPC and OPC, astrocyte, oligodendrocyte85 Neuron–glioma synapse, tumour microtube, neuronal hyperexcitability AMPAR, CX43 Perampanelc, meclofenamatec
IDH-mutant oligodendroglioma NPC and OPC, astrocyte, oligodendrocyte85,162 Paracrine, neuronal hyperexcitability NLGN3 ADAM10 inhibitorsc
H3 G34R/V-mutant DHG INPC, NPC, astrocyte152 Unknown Unknown Unknown
H3 K27M-mutant DMG OPC, astrocyte, oligodendrocyte, MESa,86,163 Neuron–glioma synapse, tumour microtube, neuronal hyperexcitability, paracrine, hub cells AMPAR, potassium channels, CX43, NLGN3 Perampanel, meclofenamate, ADAM10 inhibitors, senicapocc, gabapentinc

ADAM10, a disintegrin and metalloproteinase domain-containing protein 10; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; CX43, connexin 43; DHG, diffuse hemispheric glioma; DMG, diffuse midline glioma; HCN, hyperpolarization-activated cyclic nucleotide-gated channel; IGF1, insulin-like growth factor 1; INPC, interneuron progenitor cell; MES, mesenchymal cell; NLGN3, neuroligin 3; KCa, calcium-activated potassium channel; NPC, neural precursor cell; OPC, oligodendrocyte precursor cell; TSP1, thrombospondin 1.

a

Chiefly in older patients.

b

Studied in neurofibromatosis type 1 (NF1)-associated low-grade optic gliomas.

c

Drug mechanism has been identified but the drugs have not yet been tested in that specific glioma type.