CGRP, substance P, and PACAP from trigeminal nerves may link migraine biology to glioblastoma invasion | Research

The takeaway

Trigeminal nerve-released CGRP, substance P, and PACAP promote glioblastoma invasion through MMP upregulation, integrin activation, and cAMP-MAPK signaling, with anti-CGRP gepants and NK1 antagonist aprepitant showing anti-tumor potential.

Migraine drugs may fight brain cancer
CGRP blockers (gepants) and substance P antagonist (aprepitant)—approved for migraine—show preclinical activity against glioblastoma invasion and survival

What the researchers found

CGRP and SP upregulate MMPs and integrins in GBM. PACAP modulates cAMP-MAPK signaling. GBM spreads along trigeminal pathways on MRI. Aprepitant: GBM apoptosis. Gepants: reduce GBM invasion. Radiolabeled SP: focal alpha-therapy. Epidemiological: higher migraine antecedents in brain tumor patients.

Why it matters

This reveals that migraine drugs could be repurposed for brain cancer treatment—a completely unexpected therapeutic connection with immediate translational potential since these drugs already exist.

How the study worked

Comprehensive literature review integrating neurobiology, oncology, and pharmacology evidence for trigeminal neurogenic inflammation in GBM.

What this study cannot tell us

Review based on correlative and preclinical evidence. Epidemiological link needs stronger studies. Drug repurposing potential is based on preclinical data. Mechanisms largely demonstrated in vitro.

How to read the evidence

Literature review synthesizing preclinical, epidemiological, and imaging evidence. Novel hypothesis with multiple supporting lines of evidence.

When this study was published

Published in 2025.

The bigger picture

This paradigm-shifting review connects two seemingly unrelated conditions through shared neuropeptide biology, opening multiple drug repurposing pathways and suggesting migraine history may be a GBM risk factor worth investigating.

Questions still open

Should GBM patients with migraine history receive anti-CGRP therapy?
Could gepants slow GBM progression as adjunct therapy?
Does migraine treatment with CGRP blockers reduce brain tumor risk?

Common questions

Can migraines cause brain cancer?

Migraines do not directly cause brain cancer, but this review reveals that the same nerve chemicals (CGRP, substance P, PACAP) released during migraines can promote brain tumor growth and spread if a tumor is already present. Some studies also show people with migraines may have slightly higher rates of later brain tumor diagnosis.

Could migraine drugs treat brain cancer?

Preclinical evidence suggests yes. The CGRP-blocking gepant drugs used for migraines reduce brain tumor invasiveness, while the substance P blocker aprepitant triggers tumor cell death. Radiolabeled substance P analogues can deliver targeted radiation. These drugs could be repurposed for clinical trials in glioblastoma.

Read the original research

Trigeminal nerve-driven neurogenic inflammation linking migraine to glioblastoma invasion: a literature review.

Frontiers in immunology, 16, 1632154

View on PubMed ↗Publisher’s paper ↗

Citation

Song, Xiaoli; Zhu, Qian; Zhang, Jieying; Yang, Jin; Zhang, Xinxin; Song, Qian. (2025). Trigeminal nerve-driven neurogenic inflammation linking migraine to glioblastoma invasion: a literature review.. Frontiers in immunology, 16, 1632154. https://doi.org/10.3389/fimmu.2025.1632154