title: Pharmacotherapeutic Targeting of G Protein-Coupled Receptors in Oncology: Examples of Approved Therapies and Emerging Concepts.
abstract: G protein-coupled receptors (GPCRs) are involved in numerous physio-pathological processes, including the stimulation of cancer progression. In this regard, it should be mentioned that although GPCRs may represent major pharmaceutical targets, only a few drugs acting as GPCR inhibitors are currently used in anti-tumor therapies. For instance, certain pro-malignancy effects mediated by GPCRs are actually counteracted by the use of small molecules and peptides that function as receptor antagonists or inverse agonists. Recently, humanized monoclonal antibodies targeting GPCRs have also been developed. Here, we review the current GPCR-targeted therapies for cancer treatment, summarizing the clinical studies that led to their official approval. We provide a broad overview of the mechanisms of action of the available anti-cancer drugs targeting gonadotropin-releasing hormone, somatostatin, chemokine, and Smoothened receptors. In addition, we discuss the anti-tumor potential of novel non-approved molecules and antibodies able to target some of the aforementioned GPCRs in different experimental models and clinical trials. Likewise, we focus on the repurposing in cancer patients of non-oncological GPCR-based drugs, elucidating the rationale behind this approach and providing clinical evidence on their safety and efficacy.
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy. lappanorosamaria@yahoo.it.
authors.forename: Rosamaria
authors.initials: R
authors.lastname: Lappano
authors.affiliation: Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, Rende, Italy. marcellomaggiolini@yahoo.it.
authors.forename: Marcello
authors.identifier: http://orcid.org/0000-0002-9374-9701
authors.initials: M
authors.lastname: Maggiolini
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015195:Drug Design; D058492:Drug Repositioning; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019707:Receptors, Chemokine / Q000037:antagonists & inhibitors; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use
chemical_list: D000970:Antineoplastic Agents; D019707:Receptors, Chemokine; D043562:Receptors, G-Protein-Coupled; D007987:Gonadotropin-Releasing Hormone; D013004:Somatostatin