Involvement of the Substance P/Neurokinin-1 Receptor System in Cancer.

Abstract

New, promising molecular targets to block tumor development and new compounds capable of specifically destroying cancer cells must be urgently investigated. In recent years, the knowledge on the involvement of the substance P (SP)/ neurokinin-1 receptor (NK-1R) system in cancer has attracted increasing interest [1–5]. This has opened up new research lines and possibilities to improve cancer diagnosis and to explore new therapeutic strategies targeting tumor -specific molecular derangements since SP/NK-1R expression has been associated with cancer development and poor prognosis [1–5]. SP, an undecapeptide that binds preferentially to NK-1R, plays crucial roles in cancer development [1–6]: (1) it promotes the mitogenesis/migration of tumor cells ; (2) it exerts antiapoptotic action; (3) it increases the glycolytic rate (Warburg effect); (4) it stimulates the growth of blood vessels, and (5) tumor cells also synthesize and release SP, which acts through autocrine, paracrine, and neuroendocrine ( tumor mass) mechanisms.