Involvement of the Orexinergic System in Cancer: Antitumor Strategies and Future Perspectives

Abstract

Peptides promote the mitogenesis and migration of tumor cells, and cancer cells overexpress peptide receptors. The involvement of the orexinergic system in cancer is reviewed here, including thirteen cancer types (e.g., adrenocortical adenoma, breast, colon, gastric, liver, neuroblastoma, pancreas, prostate). An upregulation of the orexinergic system has been reported in many tumors, and orexin receptors (OXRs) mediate a dual effect: apoptosis in some tumors and a proliferative action in others. OXR antagonists or agonists are potential antitumor agents against tumors expressing OXRs. The complexities of the biological processes associated with the orexigenic system are also described in the review, as they may provide the basis for the development of new therapies: OXR dimerization/oligomerization, epigenetic mechanisms controlling the orexinergic system, possible biomarkers of this system for tumor risk/prognosis, protective effects mediated by orexins against chemotherapeutic drugs, the combination therapy of OXR antagonists/agonists with radiotherapy or chemotherapy, and the anti-inflammatory effects mediated by orexins. Taking these data into account, future therapeutic applications as well as research lines to be developed are also mentioned and discussed. This knowledge will allow for the development of antitumor strategies in the future.