Nervous System Component CGRP/RAMP1 Drives Gastrointestinal Cancer Growth
- Oct 24
- 2 min read
Gastrointestinal Cancer (GI cancer), encompassing malignancies like colorectal, gastric, esophageal, pancreatic, and liver cancers, presents an immense global health challenge, accounting for approximately one-quarter of all cancer diagnoses and one-third of cancer-related deaths worldwide. New research offers a pivotal shift in understanding these aggressive diseases by illuminating how the nervous system actively promotes tumor survival.
Australian researchers have identified a novel mechanism centering on two key nervous system components: the sensory neuropeptide Calcitonin Gene-Related Peptide (CGRP) and its co-receptor, Receptor Activity Modifying Protein 1 (RAMP1). Both CGRP and RAMP1 were found to be significant drivers of tumor proliferation in colorectal and stomach cancers.
This breakthrough confirms the profound, often critical, role of neurobiology in cancer progression. The human GI tract possesses its own intricate network, the enteric nervous system (ENS), commonly referred to as the “second brain”. Within the tumor microenvironment (TME), CGRP is present in nerve fibers infiltrating the tissue. Critically, the sources reveal that the cancer cells themselves aberrantly synthesize CGRP, thereby establishing an autocrine signaling loop that maliciously sustains the malignancy. Researchers employed sophisticated genetic engineering techniques to selectively knock out the RAMP1 receptor gene in cancer cells, resulting in a marked attenuation of tumor growth. This experimental confirmation underscores RAMP1’s vital role in this proliferative pathway.
The discovery dovetails with broader findings in neuro-oncology, which examines the indispensable roles of the nervous system in GI tumorigenesis and malignancy. Beyond CGRP/RAMP1, neural signaling pathways involving neuropeptides, β-adrenergic receptors (β-ARs), and acetylcholine receptors (AChRs) fuel aggressive tumor characteristics such as invasion, chemoresistance, and immune evasion. Furthermore, external factors like chronic stress are linked to increased GI cancer risk, often operating via neuroendocrine pathways that promote systemic low-grade inflammation.
Perhaps the most compelling implication of the CGRP/RAMP1 finding is its high translational potential for drug repurposing. Existing pharmaceutical agents designed to target CGRP and RAMP1 are already approved and widely prescribed for treating migraine headaches. This offers a unique opportunity to circumvent the time-consuming process typically associated with developing new cancer drugs, dramatically shortening the timeline for clinical application.
As lead author Dr. Pavitha Parathan noted, existing CGRP-inhibiting drugs provide a readily available means to disrupt this nerve-tumor crosstalk, potentially halting cancer progression using agents that are already well-tolerated. Dr. Lisa Mielke confirmed that the next phase involves evaluating the efficacy of existing migraine medications to combat colorectal cancer, with the aim of incorporating them into clinical trials alongside conventional therapies. This novel, neurologically targeted approach is poised to usher in a new era of precision oncology.
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