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Updated: May 28, 2025
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
Radiotherapy Plus the Neurokinin-1 Receptor Antagonist Aprepitant: A Potent Therapeutic Strategy for the Treatment of
1Research Laboratory on Neuropeptides, Institute of Biomedicine of Seville (IBIS), 41013 Seville, Spain.
Abstract:
Background: Diffuse intrinsic pontine glioma (DIPG) is a devastating childhood brainstem tumor. The median survival of DIPG is 16-24 months independent of the treatment received. Therefore, new therapeutic strategies against DIPG are urgently needed. Substance P (SP) peptide, through the neurokinin neurokinin-1 receptor (NK-1R), is involved in glioma progression. It induces glioma cell proliferation by activating MAPKs (p38 MAPK, ERK1/2, and JNK), c-Myc, AP-1, and NF-κB and induces antiapoptotic effects via PI3K/Akt/mTOR in glioma cells. SP favors glycogen breakdown that is essential for glycolysis. The SP/NK-1R system also regulates the migration and invasion of glioma cells, stimulates angiogenesis, and triggers inflammation which contributes to glioma progression. Moreover, all glioma cells express NK-1R, and NK-1R is essential for the viability of glioma cells and not of normal cells. In contrast, in glioma, NK-1R antagonists, such as the drug aprepitant, penetrate the brain and reach therapeutic concentrations, thereby inhibiting mitogenesis, inducing apoptosis, and inhibiting the breakdown of glycogen in glioma cells. In addition, they inhibit angiogenesis and exert antimetastatic and anti-inflammatory effects. The combination of radiotherapy with NK-1R antagonists produces radiosensitization and radioneuroprotection, reduces both peritumoral- and radiation-induced inflammation, and also provides antinausea and antivomiting effects. Objective: This review updates the involvement of the SP/NK-1R system in glioma promotion and progression and the potential clinical application of NK-1R antagonist drugs in DIPG therapy. Conclusions: NK-1R plays a crucial role in glioma progression and NK-1R antagonists such as aprepitant could be used in combination with radiotherapy as a potent therapeutic strategy for the treatment of patients with DIPG.
Insights
New therapies are needed for diffuse intrinsic pontine glioma (DIPG). Targeting the Substance P (SP)/neurokinin-1 receptor (NK-1R) system with antagonists like aprepitant shows promise for DIPG treatment.
Area of Science:
- Oncology
- Neuro-oncology
- Pharmacology
Background:
- Diffuse intrinsic pontine glioma (DIPG) is a fatal childhood brainstem tumor with poor prognosis.
- The Substance P (SP)/neurokinin-1 receptor (NK-1R) system is implicated in glioma growth, proliferation, and survival.
- NK-1R is highly expressed in glioma cells and essential for their viability, unlike in normal cells.
Purpose of the Study:
- To review the role of the SP/NK-1R system in glioma promotion and progression.
- To explore the potential of NK-1R antagonists in treating DIPG.
Main Methods:
- Literature review of studies on SP/NK-1R signaling in gliomas.
- Analysis of NK-1R antagonist mechanisms and clinical applications.
Main Results:
- SP/NK-1R signaling promotes glioma proliferation, survival, migration, invasion, angiogenesis, and inflammation.
- NK-1R antagonists, such as aprepitant, inhibit these processes and are brain-penetrant.
- Combination therapy with radiotherapy and NK-1R antagonists shows radiosensitization and anti-inflammatory effects.
Conclusions:
- NK-1R is a critical target in glioma progression.
- NK-1R antagonists, particularly aprepitant, represent a promising therapeutic strategy for DIPG, especially when combined with radiotherapy.
