After binding to the specific neurokinin-1 (NK-1) receptor, the peptide substance P (SP), which is widely distributed in both the central and peripheral nervous systems, induces tumor cell proliferation, angiogenesis, and migration of the tumor cells for invasion and metastasis. However, after binding to NK-1 receptors, NK-1 receptor antagonists inhibit the three above mechanisms. In fact, the antiproliferative action exerted by NK-1 receptor antagonists is because they induce cancer cells to die by apoptosis, whereas SP exerts an antiapoptotic effect. Moreover, it is known that NK-1 receptors are overexpressed in tumors and that tumor cells express several isoforms of the NK-1 receptor. All these data suggest that the SP/NK-1 receptor system could play an important role in the development of cancer; that SP may be a universal mitogen in NK-1 receptor-expressing tumor cells, and that NK-1 receptor antagonists could offer a promising therapeutic strategy for the treatment of human cancer, since they act as broad-spectrum antitumor agents. In sum, the NK-1 receptor may be a new and promising target in the treatment of human cancer.
Keywords: NK-1 receptor antagonist, substance P, mitogenesis, neoangiogenesis, metastasis, tumor cells, apoptosis, cancer, chemotherapy
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