Although in colon cancer the activation of H4R induced cell proliferation and VEGF expression, in other cancer subtypes including, melanoma, cholangiocarcinoma, oral squamous cell carcinoma, and breast, esophageal and lung cancers, histamine via H4R reduced proliferation, epithelial to mesenchymal transition, or tumor spread [11,18,38,39,40,41,42]. This evidence concerns the gene HRH4 and malignant colon neoplasm.