Glioma and Peptidergic Systems: Oncogenic and Anticancer Peptides

Abstract

Glioma cells overexpress different peptide receptors that are useful for research, diagnosis, management, and treatment of the disease. Oncogenic peptides favor the proliferation, migration, and invasion of glioma cells, as well as angiogenesis, whereas anticancer peptides exert antiproliferative, antimigration, and anti-angiogenic effects against gliomas. Other peptides exert a dual effect on gliomas, that is, both proliferative and antiproliferative actions. Peptidergic systems are therapeutic targets, as peptide receptor antagonists/peptides or peptide receptor agonists can be administered to treat gliomas. Other anticancer strategies exerting beneficial effects against gliomas are discussed herein, and future research lines to be developed for gliomas are also suggested. Despite the large amount of data supporting the involvement of peptides in glioma progression, no anticancer drugs targeting peptidergic systems are currently available in clinical practice to treat gliomas.

Keywords: anticancer peptides; glioblastoma; glioma; oncogenic peptides; peptide receptor; peptide receptor antagonist; peptidergic systems; peptides.

Figure 1

Oncogenic and anticancer peptides involved in glioma development.

Figure 2

Oncogenic peptides favoring (red rectangles) and anticancer peptides counteracting (green rectangles) the hallmarks (proliferative signaling maintenance, replicative immortality, invasion and metastasis activation, angiogenesis promotion, cell death resistance, immune destruction evasion, and energy metabolism reprogramming) responsible for glioma development.

Figure 3

Anti-glioma therapeutic strategies: peptides, monoclonal antibodies, peptide receptor knockdown, peptide receptor antagonists, miR upregulation, drugs, and inhibitors.

Figure 4

Chemical structures of peptide receptor antagonists showing anti-glioma effects. These structures were illustrated using KingDraw free software [142], except for VIPhyp, which was illustrated using the PepDraw program [143].