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.