title: Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors.
abstract: Parathyroid tumors are almost invariably associated with parathormone (PTH) hypersecretion resulting in primary (PHPT) or secondary (SHPT) hyperparathyroidism. PHPT is the third most common endocrine disorder with a prevalence of 1-2% in post-menopausal women; SHPT is a major complication of chronic kidney failure, the prevalence of which is increasing. The calciumsensing receptor (CASR) is the key molecule regulating PTH synthesis and release from the parathyroid cells in response to changes in extracellular calcium concentrations. A potent calcimimetic, cinacalcet, has been developed in the last ten years and made available for medical treatment of both PHPT and SHPT. Cinacalcet has been demonstrated to be effective in inhibiting PTH secretion, though the drug fails to normalize PTH release, both in PHPT and SHPT patients with different degrees of disease severity, including patients with parathyroid carcinomas and with MEN1-related parathyroid tumors. Here we reviewed the molecular aspects of CASR target therapy and the effect of the CASR gene single nucleotide polymorphisms. Clinical data concerning the efficacy and safety of cinacalcet in controlling hyperparathyroidism are reported, focusing on the treatment of the different types of parathyroid tumors. Finally, limits of this target therapy are analyzed, pointing out the lack of efficacy in improving kidney and bone morbidities in PHPT and cardiovascular diseases in SHPT. Though cinacalcet is a target therapeutic option for parathyroid tumors, further approaches are warranted to fully control these metabolic disorders and the underlying tumors.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Mingione
authors.forename: Chiara
authors.initials: C
authors.lastname: Verdelli
authors.forename: Annalisa
authors.initials: A
authors.lastname: Terranegra
authors.forename: Laura
authors.initials: L
authors.lastname: Soldati
authors.affiliation: Endocrinology Unit, Department of Biomedical Sciences for Health, University of Milan, IRCCS Policlinico San Donato, Via Morandi 30, 20097, San Donato Milanese (MI), Italy. sabrina.corbetta@unimi.it.
authors.forename: Sabrina
authors.initials: S
authors.lastname: Corbetta
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D057966:Calcimimetic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D020013:Calcium Signaling / Q000187:drug effects; D000069449:Cinacalcet / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D006961:Hyperparathyroidism / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D058990:Molecular Targeted Therapy; D010281:Parathyroid Hormone / Q000378:metabolism; D010282:Parathyroid Neoplasms / Q000150:complications* / Q000378:metabolism / Q000473:pathology; D044169:Receptors, Calcium-Sensing / Q000819:agonists / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor; C095550:CASR protein, human; D057966:Calcimimetic Agents; C470125:PTH protein, human; D010281:Parathyroid Hormone; D044169:Receptors, Calcium-Sensing; D000069449:Cinacalcet