Somatostatin receptor ligands in the treatment of acromegaly.
First-generation somatostatin receptors ligands (SRL) are the mainstay in the medical treatment of acromegaly, however the percentage of patients controlled with these drugs significantly varies in the different studies. Many factors are involved in the resistance to SRL. In this review, we update the physiology of somatostatin and its receptors (sst), the use of SRL in the treatment of acromegaly and the factors involved in the response to these drugs. The SRL act through interaction with the sst, which up to now have been characterized as five subtypes. The first-generation SRL, octreotide and lanreotide, are considered sst2 specific and have biochemical response rates varying from 20 to 70%. Tumor volume reduction can be found in 36-75% of patients. Several factors may determine the response to these drugs, such as sst, AIP, E-cadherin, ZAC1, filamin A and β-arrestin expression in the somatotropinomas. In patients resistant to first-generation SRL, alternative medical treatment options include: SRL high dose regimens, SRL in combination with cabergoline or pegvisomant, or the use of pasireotide. Pasireotide is a next-generation SRL with a broader pattern of interaction with sst. In the light of the recent increase of treatment options in acromegaly and the deeper knowledge of the determinants of response to the current first-line therapy, a shift from a trial-and-error treatment to a personalized one could be possible.
Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil. mgadelha@hucff.ufrj.br.|Neuroendocrinology Section and Molecular Genetics Laboratory, Secretaria Estadual de Saúde do Rio de Janeiro, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil. mgadelha@hucff.ufrj.br.
Monica R
MR
Gadelha
Neuroendocrinology Research Center/Endocrinology Section, Medical School and Hospital Universitário Clementino Fraga Filho, Universidade Federal do Rio de Janeiro, Rua Prof. Rodolpho Paulo Rocco, 9th floor, Ilha do Fundão, Rio de Janeiro, 21941-913, Brazil.|Neuroendocrinology Section and Molecular Genetics Laboratory, Secretaria Estadual de Saúde do Rio de Janeiro, Instituto Estadual do Cérebro Paulo Niemeyer, Rio de Janeiro, Brazil.
Luiz Eduardo
LE
Wildemberg
Neuroendocrine Unit, Division of Endocrinology and Metabolism, Hospital das Clinicas, University of Sao Paulo Medical School, São Paulo, Brazil.
Marcello D
MD
Bronstein
Endocrinology Unit, Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.
Federico
F
Gatto
Endocrinology Unit, Department of Internal Medicine and Medical Specialties and Center of Excellence for Biomedical Research, University of Genoa, Genoa, Italy.|IRCCS AOU San Martino-IST Genoa, Genoa, Italy.
Diego
D
Ferone
D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D015282:Octreotide / Q000627:therapeutic use; D010456:Peptides, Cyclic / Q000627:therapeutic use; D017481:Receptors, Somatostatin / Q000819:agonists / Q000378:metabolism*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use
D010456:Peptides, Cyclic; D017481:Receptors, Somatostatin; C060347:lanreotide; D013004:Somatostatin; C517782:pasireotide; D015282:Octreotide
Acromegaly; Lanreotide; Octreotide; Pasireotide; Somatostatin receptor ligands; Somatostatin receptors