title: Resistance to octreotide LAR in acromegalic patients with high SSTR2 expression: analysis of AIP expression.
abstract: We present here the clinical and molecular data of two patients with acromegaly treated with octreotide LAR after non-curative surgery, and who presented different responses to therapy. Somatostatin receptor type 2 and 5 (SSTR2 and SSTR5), and aryl hydrocarbon receptor-interacting protein (AIP) expression levels were analyzed by qPCR. In both cases, high SSTR2 and low SSTR5 expression levels were detected; however, only one of the patients achieved disease control after octreotide LAR therapy. When we analyzed AIP expression levels of both cases, the patient whose disease was controlled after therapy exhibited AIP expression levels that were two times higher than the patient whose disease was still active. These two cases illustrate that, although the currently available somatostatin analogs bind preferentially to SSTR2, some patients are not responsive to therapy despite high expression of this receptor. This difference could be explained by differences in post-receptor signaling pathways, including the recently described involvement of AIP.
authors.affiliation: Endocrinology Division, Clementino Fraga Filho University Hospital, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
authors.forename: Leandro
authors.initials: L
authors.lastname: Kasuki
authors.forename: Leandro M
authors.initials: LM
authors.lastname: Colli
authors.forename: Paula C L
authors.initials: PC
authors.lastname: Elias
authors.forename: Margaret de
authors.initials: Md
authors.lastname: Castro
authors.forename: Mônica R
authors.initials: MR
authors.lastname: Gadelha
mesh_terms: D000172:Acromegaly / Q000188:drug therapy* / Q000378:metabolism; D000328:Adult; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D015282:Octreotide / Q000627:therapeutic use*; D010911:Pituitary Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D017481:Receptors, Somatostatin / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D047908:Intracellular Signaling Peptides and Proteins; D017481:Receptors, Somatostatin; C103265:aryl hydrocarbon receptor-interacting protein; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2; D015282:Octreotide