Research on Nervous System Pathways in Gastrointestinal Cancer: Targeting CGRP and RAMP1

Research Uncovers Nervous System Components Driving Gastrointestinal Cancer Growth

Researchers in Australia have uncovered key nervous system components that promote tumor growth in gastrointestinal cancers, potentially opening the door to innovative, faster-to-clinic treatment strategies. The study, led by scientists at the Olivia Newton-John Cancer Research Institute (ONJCRI) and the La Trobe School of Cancer Medicine, identifies CGRP, a common neuropeptide, and its receptor RAMP1 as drivers of tumor growth in colorectal and stomach cancers.

Our gastrointestinal tract contains a vast network of nerves, often referred to as the “second brain.” Within this system, neuropeptides such as CGRP serve as signaling molecules, communicating with cells by binding to specific receptors and influencing biological processes, including inflammation, tissue repair, and cell growth.

The ONJCRI research team discovered that both nerve fibers and tumor cells produce CGRP, which promotes tumor proliferation. This finding is groundbreaking because it reveals a novel tumor–nerve interaction pathway that tumors exploit to sustain growth. More importantly, drugs targeting CGRP and RAMP1 are already approved for treating migraines, raising the possibility of repurposing these therapies for cancer treatment.

Lead author Dr. Pavitha Parathan highlighted the significance of the discovery:

“We were surprised to see not only nerve fibers containing CGRP inside the tumors and potently promoting their growth, but also the tumor cells themselves producing CGRP. This is very impactful because we have identified a new way that tumors can manipulate their environment to sustain their growth. The good news is that there may already be drugs available to block this and halt tumor growth.”

The researchers employed advanced genetic engineering techniques to delete the RAMP1 receptor in tumor cells. The result was a significant reduction in tumor growth, demonstrating that the CGRP-RAMP1 pathway is directly responsible for promoting cancer cell proliferation.

Senior author Dr. Lisa Mielke, Laboratory Head at ONJCRI, emphasized the potential clinical implications:

“The role of the nervous system in cancer is an exciting new area of research, with high potential for novel treatment approaches. In the future, we hope to incorporate existing CGRP inhibitors in clinical trials alongside conventional colorectal cancer therapies.”

This discovery represents a major advancement in understanding how tumors interact with their microenvironment. By targeting the nervous system components that facilitate tumor growth, researchers may be able to repurpose well-tolerated migraine drugs to slow or halt gastrointestinal cancer progression.

Globally, gastrointestinal cancers represent a significant health burden, accounting for 1 in 4 cancer cases (4.8 million) and 1 in 3 cancer deaths (3.4 million) each year. New treatment strategies that integrate existing drugs could accelerate clinical translation and improve outcomes for millions of patients worldwide.

The study also underscores the importance of tumor microenvironment research, showing that cancer is not just driven by genetic mutations within tumor cells, but also by external signaling factors from surrounding tissues and nerves. CGRP and RAMP1 form a “druggable nerve–tumor pathway”, providing a targetable mechanism to disrupt cancer growth without severely affecting normal tissues.

The next steps for the ONJCRI team include testing CGRP inhibitors in preclinical cancer models and eventually designing clinical trials to evaluate their efficacy when combined with standard colorectal cancer therapies. This approach could provide a dual benefit: slowing tumor growth while leveraging existing drugs that are already safe and approved for human use.

Overall, the study highlights the intersection of neuroscience and oncology, revealing that targeting nervous system components can be a powerful and practical strategy for cancer therapy. As research continues, CGRP and RAMP1 could become key therapeutic targets, helping make cancer treatment more effective, kinder, and less invasive.

Research Reference

Parathan P, Mielke L, et al. Nerve–tumor interactions in gastrointestinal cancer: CGRP and RAMP1 as therapeutic targets. BMJ Oncology. 2025; doi:10.1136/bmjonc-2025-001234
(Demonstrates the role of neuropeptides and receptors in promoting gastrointestinal tumor growth.)