NK-1 as a melanoma target

Melanoma expresses both neurokinin-1 (NK-1) receptors and substance P (SP). After binding to the NK-1 receptor, SP induces tumor cell proliferation in melanoma cells, whereas after binding to the same NK-1 receptor, antagonists inhibit melanoma cell proliferation and cause tumor cell death by apoptosis. Thus, the NK-1 receptor could be a new and promising target in melanoma therapy.

This review provides an overview of the underlying mechanism of action of the SP/NK-1 receptor system, and NK-1 receptor antagonists in human melanoma, over the last 7 years.

In stages III - IV, no effective treatment exists for melanoma and hence there is an urgent need to improve therapy in melanoma patients. The NK-1 receptor is a promising new target in human melanoma treatment, since preclinical assays (most of them in vitro assays) have reported that NK-1 receptor antagonists exert an antitumor action against melanoma. The NK-1 receptor antagonist aprepitant is used in clinical practice and exerts an antitumor action against human melanoma in vitro. In the future, such antitumor action should be tested in human clinical trials. This should be faster compared with less investigated NK-1 receptor antagonists, because a great part of the required safety and characterization studies for aprepitant have already been carried out.