Potential inhibition of the neuro-neoplastic interactions: the clue of a GPCR-targeted therapy.

Abstract

Other sections of this monograph, dedicated to neuronal activities in tumor tissue, have highlight the chief influence of neurotrophins, neurotransmitters, adhesion, guidance molecules and different nerve cell markers in the progression, but also for the prognostic, therapy and survey of cancers. The G-protein-coupled receptors (GPCR) are among the most successful and promising target proteins for drug discovery and therapeutic research. GPCR are frequently overexpressed in cancer cells, an interesting property for tumor imaging or for a targeted radiotherapy, using radiolabeled ligand derivatives. The tumor microenvironment contains a number of GPCR ligands (e.g., bioactive peptides, biogenic amines, purins, chemokines), known to regulate the proliferation, migration or survival of both tumoral and neural cells and that may be key actors of the neuro-neoplastic interactions. Here will be reviewed the potential utilization of substances that target a selected choice of GPCR, especially neuropeptide receptors, for a novel concept of therapy, concerning the numerous types of cancers where neurons infiltrate the tumoral mass or those where the malignant cells invade nerve branches (perineural invasion). Some molecular mechanisms linked to these GPCR (or linking GPCR to other types of membrane receptors or co-receptors), involved in these processes, will also be considered.