Title:Molecular and Clinical Aspects of the Target Therapy with the Calcimimetic Cinacalcet in the Treatment of Parathyroid Tumors
Volume: 15
Issue: 7
Author(s): Alessandra Mingione, Chiara Verdelli, Annalisa Terranegra, Laura Soldati and Sabrina Corbetta
Affiliation:
Keywords:
Calcium-sensing receptor, cinacalcet, parathyroid tumors, primary hyperparathyroidism, single nucleotide
polymorphisms.
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.
