The Pain Peptide Substance P Drives Colorectal Cancer Spread — And a Nausea Drug Can Block It

Human SW480 colorectal cancer cells were treated with varying concentrations of substance P, alone or combined with aprepitant. Cell viability was measured using the Resazurin assay. Metastatic potential was assessed by gelatin zymography (to measure MMP-2 and MMP-9 enzyme activity), RT-qPCR (gene expression), Western blot (protein expression), and scratch wound assay (cell migration).

Colorectal cancer is among the deadliest cancers, and metastasis — not the primary tumor — is what kills most patients. Finding that an already-approved drug (aprepitant) can block a key metastatic pathway opens the door to rapid clinical testing. Drug repurposing avoids the years of safety testing required for new drugs, potentially bringing an anti-metastatic therapy to patients faster.

Substance P and its receptor NK1R have been implicated in multiple cancer types, not just colorectal. This study adds to a growing body of evidence that neuropeptides — molecules traditionally associated with pain and inflammation — play active roles in cancer progression. Aprepitant is already in oncology clinics as an anti-nausea drug during chemotherapy. If it also has anti-metastatic properties, patients might already be receiving some unrecognized benefit, and intentional therapeutic use could significantly improve outcomes.

This was an in vitro study using a single colorectal cancer cell line (SW480), which may not represent the full heterogeneity of colorectal cancers. No animal models or clinical data were included. The concentrations of substance P and aprepitant used in the lab may not reflect what occurs in the tumor microenvironment. The study did not assess invasion through Matrigel or other 3D models that better simulate in vivo metastasis.