The Neurokinin-1 Receptor Antagonist Aprepitant: An Intelligent Bullet against Cancer?

SIMPLE SUMMARY: Due to the lack of selectivity and the severe side-effects, cytostatics are the drugs of the present but not of the future and consequently new anticancer strategies must be developed. After binding to the neurokinin-1 receptor (NK-1R), NK-1R antagonists exert antitumor actions (antiproliferative, antimetastasis), are safe and do not cause serious side-effects. Aprepitant, a non-peptide NK-1R antagonist, is currently used in clinical practice as antiemetic but this compound also shows antitumor effects against a broad-spectrum of cancers. Our aim is to review the multiple antitumor actions exerted by aprepitant and to show the potential use of this drug as an antitumor agent. Aprepitant could be considered as an intelligent bullet against cancer. The data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent. The administration of aprepitant in cancer patients to prevent recurrence/metastasis after surgical procedures, thrombosis and thromboembolism is also suggested. ABSTRACT: Neurokinin-1 receptor (NK-1R) antagonists exert antitumor action, are safe and do not cause serious side-effects. These antagonists (via the NK-1R) exert multiple actions against cancer: antiproliferative and anti-Warburg effects and apoptotic, anti-angiogenic and antimetastatic effects. These multiple effects have been shown for a broad spectrum of cancers. The drug aprepitant (an NK-1R antagonist) is currently used in clinical practice as an antiemetic. In in vivo and in vitro studies, aprepitant also showed the aforementioned multiple antitumor actions against many types of cancer. A successful combination therapy (aprepitant and radiotherapy) has recently been reported in a patient suffering from lung carcinoma: the tumor mass disappeared and side-effects were not observed. Aprepitant could be considered as an intelligent bullet against cancer. The administration of aprepitant in cancer patients to prevent recurrence and metastasis after surgical procedures, thrombosis and thromboembolism is discussed, as is the possible link, through the substance P (SP)/NK-1R system, between cancer and depression. Our main aim is to review the multiple antitumor actions exerted by aprepitant, and the use of this drug is suggested in cancer patients. Altogether, the data support the reprofiling of aprepitant for a new therapeutic use as an antitumor agent.