The sensory neuropeptide CGRP promotes colorectal and gastric cancer cell growth through its receptor RAMP1, with tumors not only responding to but also producing their own CGRP—revealing a new tumor-nerve axis therapeutic target.
>50% of tumor cells express RAMP1CGRP receptor expression in colorectal and gastric cancers was linked to worse survival and tumor-driven CGRP production
What the researchers found
RAMP1 expression was associated with reduced survival in CRC and GC. Over 50% of CRC and 60% of GC cells expressed RAMP1. Tumor cells themselves produced CGRP (not just nerves). CGRP stimulation enhanced tumor growth in a RAMP1-dependent manner, activating proliferation, metabolism, and migration pathways.
Why it matters
This study reveals that gastrointestinal cancers can exploit and even produce neuropeptides to fuel their own growth, opening a new therapeutic avenue. CGRP-blocking drugs already exist for migraine—they could potentially be repurposed for cancer treatment.
The numbers in context
180 patient samples analyzed using multiplex immunohistochemistry. Included primary colorectal cancer, CRC liver metastases, and gastric cancers. RAMP1 expression correlated with pathological features and molecular subtypes. TCGA data used for survival analysis.
How the study worked
Analysis of 180 patient samples using multiplex immunohistochemistry, TCGA survival data analysis, in vitro stimulation assays on tumor cell lines and patient-derived organoids, and RNA sequencing for mechanistic pathway analysis.
Who was studied
Patients with colorectal cancer (primary and liver metastases) and gastric cancer
What this study cannot tell us
Primarily correlative in patient samples; mechanistic work limited to in vitro and organoid models. No in vivo tumor treatment studies. CGRP-blocking therapies for cancer remain untested. Association between RAMP1 expression and survival does not prove causation.
How to read the evidence
Strong translational study combining large patient cohort analysis (180 samples + TCGA), functional in vitro work, patient-derived organoids, and RNA sequencing. Well-designed but lacks in vivo therapeutic validation.
When this study was published
Published in 2025; represents cutting-edge research on the tumor-nerve axis in GI cancers.
The bigger picture
This work adds to growing evidence that the nervous system is not just a bystander in cancer but an active participant. The discovery that tumors produce their own CGRP creates an autocrine growth loop that could be targeted therapeutically, potentially with existing anti-CGRP drugs developed for migraines.
Questions still open
- Could anti-CGRP drugs used for migraines (erenumab, fremanezumab) be repurposed for GI cancer treatment?
- Is tumor-derived CGRP an autocrine growth signal or does it also recruit nerve growth toward the tumor?
- Could RAMP1 expression serve as a biomarker for patient selection in anti-CGRP cancer therapy trials?
Common questions
What is CGRP and how does it relate to cancer?
Could migraine drugs be used to treat GI cancers?
Read the original research
Sensory neuropeptide CGRP and its co-receptor RAMP1 drive tumour cell growth in gastrointestinal cancers.
BMJ oncology, 4(1), e000842
Citation
Parathan, Pavitha; Tran, Kelly; Neil, Liam; Tan, Tao; Carli, Annalisa L E; Liao, Yang; Mouradov, Dmitri; Da Gama Duarte, Jessica; Huber, Anne; Pal, Bhupinder; Gibbs, Peter; Sieber, Oliver M; Chiu, Isaac M; Kearney, Conor J; Shi, Wei; Mariadason, John M; Williams, David S; Buchert, Michael; Mielke, Lisa A. (2025). Sensory neuropeptide CGRP and its co-receptor RAMP1 drive tumour cell growth in gastrointestinal cancers.. BMJ oncology, 4(1), e000842. https://doi.org/10.1136/bmjonc-2025-000842