# The Involvement of the Peptidergic Systems in Breast Cancer Development

## TL;DR

This paper explores how peptides and their receptors can both promote and inhibit breast cancer, suggesting they could be used to develop new treatments.

## Contribution

The paper systematically categorizes peptides with oncogenic, anticancer, or dual effects and highlights their potential as antitumor agents.

## Key findings

- Peptides and their receptors can inhibit cancer cell proliferation, migration, and invasion.
- Peptidergic systems offer potential for imaging, diagnosis, and targeted therapies in breast cancer.
- Peptide receptor agonists and antagonists show promise as antitumor agents with diverse mechanisms.

## Abstract

Breast cancer cells overexpress peptide receptors and interact with peptides that (a) exert an oncogenic action, (b) exert an anticancer action or (c) exert dual oncogenic and anticancer effects. This indicates that peptides, as well as peptide receptor agonists and antagonists, may serve as antitumor agents due to their diverse actions against breast cancer development, including the inhibition of cell proliferation, migration, and invasion, the induction of apoptosis, and anti-angiogenic effects. Peptidergic systems have great anti-breast-cancer clinical potential which must be exploited and developed. A greater understanding of the roles played by the peptidergic systems in breast cancer will serve to improve diagnosis and treatment.

The current known data on the involvement of the peptidergic systems in breast cancer progression is overwhelmingly vast. Peptidergic systems are useful tools for imaging, diagnosis, prognosis and treatment of breast cancer. These systems play a crucial role in both basic and clinical breast cancer research by enabling the exploration of novel molecular mechanisms, signaling pathways, and the development of effective drug design strategies. Breast cancer cells overexpress peptide receptors; at the same time they are known to interact with peptides that (a) exert an oncogenic action (adrenomedullin 2, endothelin, gastrin-releasing peptide, neurokinin A, neuromedin, neuropeptide Y, neurotensin, substance P, vasoactive intestinal peptide), (b) exert an anticancer action (angiotensin (1–7), ghrelin, peptide YY) or (c) exert dual oncogenic and anticancer effects (adrenomedullin, angiotensin II, bradykinin, corticotropin-releasing factor, β-endorphin, glucagon-like peptide 1, gonadotropin-releasing hormone, kisspeptin, methionine-enkephalin, oxytocin). This indicates that peptides, as well as peptide receptor agonists and antagonists, may serve as antitumor agents due to their diverse actions against breast cancer development, including the inhibition of cell proliferation, migration and invasion, induction of apoptosis, and anti-angiogenesis. Multiple strategies have been developed to combat breast cancer, including peptide receptor silencing; antibodies conjugated to specific signaling proteins; antibodies targeting specific peptide receptors or oncogenic peptides; and the use of peptides or peptide receptor agonists/antagonists loaded with antitumor cargo. Future lines of research are suggested in breast cancer using promising anti-breast-cancer peptide receptor antagonists (HOE-140, exendin (9–39), bosentan, macitentan, PD168,368, CGP71,683A, SR48,692, aprepitant) or agonists (FR190,997, semaglutide, exendin 4, goserelin) mentioned in this review. Peptidergic systems have tremendous anti-breast-cancer clinical potential which must be exploited and developed. Taken together, the available data highlight the enormous promise of translational research into breast cancer and peptidergic systems for the development of effective treatments. A full understanding of the roles played by the peptidergic systems in breast cancer will serve to improve diagnosis and treatment.