Emerging Role of the Macrophage Migration Inhibitory Factor Family of Cytokines in Neuroblastoma. Pathogenic Effectors and Novel Therapeutic Targets?

• Published in: Molecules (Basel, Switzerland) Vol. 25; no. 5; p. 1194
• Main Authors: Cavalli, Eugenio, Ciurleo, Rosella, Petralia, Maria Cristina, Fagone, Paolo, Bella, Rita, Mangano, Katia, Nicoletti, Ferdinando, Bramanti, Placido, Basile, Maria Sofia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 06.03.2020; MDPI
• Subjects: Age; Animals; Biomarkers, Tumor; Cancer; Cell cycle; Cytokines; Cytokines - antagonists & inhibitors; Cytokines - genetics; Cytokines - metabolism; d -dopachrome tautomerase; Disease Management; Disease Susceptibility; Dopachrome isomerase; Drug Discovery; Drug Repositioning; Homology; Humans; Immunotherapy; Intramolecular Oxidoreductases - antagonists & inhibitors; Intramolecular Oxidoreductases - genetics; Intramolecular Oxidoreductases - metabolism; Kinases; Macrophage migration inhibitory factor; macrophage migration inhibitory factor inhibitors; Macrophage Migration-Inhibitory Factors - antagonists & inhibitors; Macrophage Migration-Inhibitory Factors - genetics; Macrophage Migration-Inhibitory Factors - metabolism; Medical prognosis; Metastasis; Molecular Targeted Therapy; Multigene Family; Neuroblastoma; Neuroblastoma - drug therapy; Neuroblastoma - etiology; Neuroblastoma - metabolism; Neuroblastoma - pathology; Patients; Pediatrics; Phosphorylation; Physiology; Polymorphism; Proteins; Quality of life; Review; Signal transduction; Stem cells; Therapeutic applications; Transplants & implants; Tumor cell lines; Tumors; neuroblastoma; macrophage migration inhibitory factor; macrophage migration inhibitory factor inhibitors; d-dopachrome tautomerase
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules25051194

Neuroblastoma (NB) is the most frequent extracranial pediatric tumor. Despite the current available multiple therapeutic options, the prognosis for high-risk NB patients remains unsatisfactory and makes the disease a clear unmet medical need. Thus, more tailored therapeutic approaches are warranted to improve both the quality of life and the survival of the patients. Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that plays a key role in several diseases, including cancer. Preclinical and clinical studies in NB patients convergently indicate that MIF exerts pro-tumorigenic properties in NB. MIF is upregulated in NB tumor tissues and cell lines and it contributes to NB aggressiveness and immune-escape. To date, there are only a few data about the role of the second member of the MIF family, the MIF homolog d-dopachrome tautomerase (DDT), in NB. Here, we review the preclinical and clinical studies on the role of the MIF family of cytokines in NB and suggest that MIF and possibly DDT inhibitors may be promising novel prognostic and therapeutic targets in NB management.