Miguel Munoz*, Marisa Rosso and Rafael Covenas Pages 1465 - 1476 ( 12 )
Background: Many studies support the involvement of the substance P (SP)/neurokinin-1 receptor (NK-1R) system in cancer. SP, after binding to the NK-1R, regulates cancer cell proliferation, induces cell migration and invasion, which are steps of the metastatic process, exerts an antiapoptotic effect, and triggers endothelial cell proliferation necessary for neoangiogenesis. Lung cancer is the first cause of cancer-related deaths in the western world and despite trials using cytotoxic chemotherapeutic agents, no significant progress in extending the survival of patients suffering the disease has been reported. New strategies must be developed. The NK-1R is involved in the viability of lung cancer cells. In lung cancer, SP and NK-1Rs are expressed in human samples while human non-small-(NSCLC) and small (SCLC)-cell lung cancer cells overexpress these receptors. Non-peptide NK-1R antagonists (aprepitant (Emend), L-733,060, L-732,138) and the peptide NK- 1R antagonist [D-Arg1, D-Phe5, D-Trh7,9, Leu11]-SP exert, via the NK-1R and in a concentrationdependent manner, an antiproliferative action against human lung cancer cells (inhibit cell proliferation and induce the death of tumor cells by apoptosis). NK-1R antagonists also inhibit the migration of tumor cells and exert an antiangiogenic action. The SP/NK-1R system is an important target for the treatment of lung cancer and NK-1R antagonists could act as specific drugs against lung cancer cells. The use of NK-1R antagonists (e.g., the drug aprepitant, used as antiemetic in clinical practice) as antitumor agents could be a promising therapeutic innovation.
Conclusion: In this review, we update and discuss the data regarding the possible use of NK-1R antagonists in the treatment of lung cancer.
Substance P, non-small-cell lung cancer cell, small-cell lung cancer cell, aprepitant, antitumor, apoptosis, metastasis, signalling pathway.
Hospital Infantil Virgen del Rocio, Unidad de Cuidados Intensivos Pediatricos, Av. Manuel Siurot s/n, 41013-Sevilla, Research Laboratory on Neuropeptides (IBIS), Virgen del Rocio University Hospital, Sevilla, Institute of Neurosciences of Castilla y Leon (INCYL), Laboratory of Neuroanatomy of the Peptidergic Systems, University of Salamanca, Salamanca