Substance P/NK-1R signaling promotes glioblastoma growth, anti-apoptosis, invasion, and vascularization, making NK-1R antagonists a promising additional therapeutic target for this deadly brain tumor.
<1 yearoverall survival for GBM patients, highlighting urgent need for new therapeutic approaches like NK-1R antagonists
What the researchers found
SP/NK-1R signaling controls GBM cell growth, exerts anti-apoptotic effects, stimulates invasion/metastasis, and activates vascularization. NK-1R antagonists can block these cancer-promoting effects and represent a potential additional treatment target.
Why it matters
GBM survival remains dismal despite decades of research. Repurposing NK-1R antagonists (already FDA-approved for other uses) could provide an accessible new treatment option, either alone or in combination with standard therapies.
The numbers in context
GBM survival <1 year; NK-1R antagonists inhibited growth, invasion, and apoptosis resistance in preclinical GBM studies.
How the study worked
Review of published literature on substance P/NK-1R pathway roles in glioblastoma and other cancers, with evaluation of NK-1R antagonist therapeutic potential.
Who was studied
Preclinical glioblastoma models and NK-1R antagonist studies
What this study cannot tell us
Review-level evidence — clinical trials of NK-1R antagonists in GBM have not been conducted. Blood-brain barrier penetration of NK-1R antagonists varies. The relative contribution of SP/NK-1R signaling versus other oncogenic pathways in GBM is unclear.
How to read the evidence
Review of preclinical and mechanistic evidence supporting NK-1R as a GBM target. No clinical trial data for this indication yet.
When this study was published
Published in 2021. NK-1R antagonist repurposing for cancer continues to be explored in preclinical and early clinical settings.
The bigger picture
The discovery that neuropeptides drive brain tumor progression reveals the nervous system as an active participant in cancer biology. Targeting neurotransmitter pathways in brain cancer represents an innovative approach that leverages the brain's own signaling molecules.
Questions still open
- Would NK-1R antagonists enhance the efficacy of temozolomide or radiation in GBM?
- What is the optimal NK-1R antagonist for brain tumor penetration?
- Could NK-1R pathway biomarkers predict which GBM patients would benefit most?
Common questions
What is glioblastoma?
How could an anti-nausea drug treat brain cancer?
Read the original research
Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme.
Current medicinal chemistry, 28(24), 4877-4892
Citation
Afshari, Amir R; Motamed-Sanaye, Ali; Sabri, Hamed; Soltani, Arash; Karkon-Shayan, Sepideh; Radvar, Sarvin; Javid, Hossein; Mollazadeh, Hamid; Sathyapalan, Thozhukat; Sahebkar, Amirhossein. (2021). Neurokinin-1 Receptor (NK-1R) Antagonists: Potential Targets in the Treatment of Glioblastoma Multiforme.. Current medicinal chemistry, 28(24), 4877-4892. https://doi.org/10.2174/0929867328666210113165805