title: Neurokinin-1 receptor antagonists as antitumor drugs in gastrointestinal cancer: A new approach.
abstract: Gastrointestinal (GI) cancer is the term for a group of cancers affecting the digestive system. After binding to the neurokinin-1 (NK-1) receptor, the undecapeptide substance P (SP) regulates GI cancer cell proliferation and migration for invasion and metastasis, and controls endothelial cell proliferation for angiogenesis. SP also exerts an antiapoptotic effect. Both SP and the NK-1 receptor are located in GI tumor cells, the NK-1 receptor being overexpressed. By contrast, after binding to the NK-1 receptor, NK-1 receptor antagonists elicit the inhibition (epidermal growth factor receptor inhibition) of the proliferation of GI cancer cells in a concentration-dependent manner, induce the death of GI cancer cells by apoptosis, counteract the Warburg effect, inhibit cancer cell migration (counteracting invasion and metastasis), and inhibit angiogenesis (vascular endothelial growth factor inhibition). NK-1 receptor antagonists are safe and well tolerated. Thus, the NK-1 receptor could be considered as a new target in GI cancer and NK-1 receptor antagonists (eg, aprepitant) could be a new promising approach for the treatment of GI cancer.
authors.affiliation: Rafael Coveñas, Institute of Neurosciences of Castilla and León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, Salamanca, Spain.
authors.forename: Miguel
authors.initials: M
authors.lastname: Muñoz
authors.affiliation: Rafael Coveñas, Institute of Neurosciences of Castilla and León (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, Salamanca, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: Coveñas
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D009361:Neoplasm Invasiveness; D064729:Neurokinin-1 Receptor Antagonists / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D064729:Neurokinin-1 Receptor Antagonists