The Neurotensinergic System: A Target for Cancer Treatment

Abstract

Background: The scientific interest regarding the involvement of peptides in cancer has increased in the last few years. In tumor cells, the overexpression of peptides and their receptors is known, and new therapeutic targets for the treatment of cancer have been suggested. The overexpression of the neurotensinergic system has been associated with poor prognosis, tumor size, higher tumor aggressiveness, increased relapse risk, and worse sensitivity to chemotherapy agents.

Objective: The aim of this review is to update the findings regarding the involvement of the neurotensinergic system in cancer to suggest anticancer therapeutic strategies targeting this system. The neurotensin (NT) precursor, NT and its receptors (NTR), and the involvement of the neurotensinergic system in lung, breast, prostate, gastric, colon, liver, and pancreatic cancers, glioblastoma, neuroendocrine tumors, and B-cell leukemia will be mentioned and discussed as well as the signaling pathways mediated by NT. Some research lines to be developed in the future will be suggested, such as molecules regulating the expression of the NT precursor, the influence of the diet in the development of tumors, molecules and signaling pathways activated by NT, and antitumor therapeutic strategies targeting the neurotensinergic system.

Conclusion: NT, via the NTR, exerts oncogenic (tumor cell proliferation, invasion, migration, angiogenesis) and antiapoptotic effects, whereas NTR antagonists inhibit these effects. NTR expression can be used as a diagnostic tool/therapeutic target, and the administration of NTR antagonists as antitumor drugs could be a therapeutic strategy to treat tumors overexpressing NTR.

Keywords: Neurotensin; breast; gastrointestinal; liver; lung; neurotensin receptor antagonists; prostate; signaling pathways; tumor.