Involvement of the Opioid Peptide Family in Cancer Progression

Abstract

Peptides mediate cancer progression favoring the mitogenesis, migration, and invasion of tumor cells, promoting metastasis and anti-apoptotic mechanisms, and facilitating angiogenesis/lymphangiogenesis. Tumor cells overexpress peptide receptors, crucial targets for developing specific treatments against cancer cells using peptide receptor antagonists and promoting apoptosis in tumor cells. Opioids exert an antitumoral effect, whereas others promote tumor growth and metastasis. This review updates the findings regarding the involvement of opioid peptides (enkephalins, endorphins, and dynorphins) in cancer development. Anticancer therapeutic strategies targeting the opioid peptidergic system and the main research lines to be developed regarding the topic reviewed are suggested. There is much to investigate about opioid peptides and cancer: basic information is scarce, incomplete, or absent in many tumors. This knowledge is crucial since promising anticancer strategies could be developed alone or in combination therapies with chemotherapy/radiotherapy.

Low-Dose Naltrexone as an Adjuvant in Combined Anticancer Therapy

“…According to the authors, the presented results from the in vitro and in vivo models suggest that LDN has a high anticancer potential, and that its mechanism of action is pleiotropic. There are studies describing the use of OGF as a potential anticancer therapy [ 77 , 78 , 79 ]. The fact that the therapeutic effects of LDN in the context of inhibiting carcinogenesis are primarily associated with the transient inhibition of the OGF–OGFr pathway and a compensatory increase in OGF concentration further confirms the need for more research on the use of LDN in the context of treating oncological diseases.…”

Antitumor Strategies Targeting Peptidergic Systems

“…Many in vitro and in vivo experiments have demonstrated the fundamental roles that peptides and their receptors play in cancer progression [1]. After binding to their respective receptors, peptides promote proliferative and antiproliferative effects in cancer cells: the same peptide (e.g., galanin, orexin) can exert both effects in tumor cells (the reason for this being the G protein type and the subtype of receptor involved, for example, galanin 1, 2, and 3 receptors), whereas other peptides (e.g., substance P, neurotensin) mainly induce a proliferative action (oncogenic effect) in many types of tumor cells [2,3].…”