2015
DOI: 10.2147/rred.s78255
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Profile of pegvisomant in the management of acromegaly: an evidence based review of its place in therapy

Abstract: Pegvisomant (PEG) is a genetically engineered growth hormone (GH) analog able to bind and block the GH receptor. PEG blocks all metabolic effects of GH hypersecretion, normalizes insulin-like growth factor I (IGF-I) level and paradoxically produces an increase in GH secretion. When PEG was commercialized, there were some concerns regarding whether the increased GH secretion could cause growth of the residual tumor or cause the overcoming of receptor blockade with loss of efficacy. PEG commercialization was fol… Show more

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Cited by 7 publications
(8 citation statements)
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“…Escape to PEG has been previously reported, but, to our knowledge, there is no precise and specific definition for this phenomenon in the literature, and it has not been fully characterized. Several factors recently reviewed may influence the required PEG dose and could be related to the development of escapes to PEG, including sex, weight, baseline GH and IGF‐I levels, previous radiotherapy, diabetes mellitus, GH‐receptor (GHR) genotype and/or IGF‐I and IGFBP3 polymorphisms. Additionally, the progressive clearance of previous SSA treatments, long‐term changes in GH and GHBP levels or modifications in GHR expression induced by treatments could also promote the need for increasing doses of PEG.…”
Section: Discussionmentioning
confidence: 99%
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“…Escape to PEG has been previously reported, but, to our knowledge, there is no precise and specific definition for this phenomenon in the literature, and it has not been fully characterized. Several factors recently reviewed may influence the required PEG dose and could be related to the development of escapes to PEG, including sex, weight, baseline GH and IGF‐I levels, previous radiotherapy, diabetes mellitus, GH‐receptor (GHR) genotype and/or IGF‐I and IGFBP3 polymorphisms. Additionally, the progressive clearance of previous SSA treatments, long‐term changes in GH and GHBP levels or modifications in GHR expression induced by treatments could also promote the need for increasing doses of PEG.…”
Section: Discussionmentioning
confidence: 99%
“…Several reasons for this lower than expected efficacy of PEG in observational studies have been recently outlined . For instance, problems with dose titration or compliance, change in the IGF‐I measuring method, temporary loss of IGF‐I control requiring dose adjustments or the use of different criteria to assess IGF‐I normalization in preclinical versus observational and clinical studies (IGF‐I normalization at any time versus IGF‐I normalization at last evaluation) have been identified.…”
Section: Introductionmentioning
confidence: 99%
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“…El GHR está conformado por un dominio N-terminal que contiene la región extracelular donde se une la hormona, un dominio transmembrana hidrófobo y un dominio C-terminal que contiene estructuras importantes en la señalización intercelular (19,21). El receptor se elimina mediante su degradación proteolítica y un proceso continuo de internalización dependiente de ubiquitina y degradación endolisosómica (29). La escisión proteolítica del dominio extracelular genera GHBP (19,23) y aunque su función no es clara, se considera que funciona como un reservorio de GH, modula su actividad al competir con el GHR (19), reduce la tasa de eliminación (17) y sirve como marcador de la renovación de GHR (20).…”
Section: Ghr E Interacción Gh-ghrunclassified
“…El GHR carece de actividad quinasa intrínseca, por lo cual induce al reclutamiento y la activación de tirosinas-quinasas citoplasmáticas para la señalización, como Janus quinasa 2 (JAK2) (17,19), constituyendo así la más utilizada por el GHR (19). Esta unión desencadena la fosforilación de la quinasa 2 de Janus (JAK2) que induce al reclutamiento y la posterior fosforilación de STATs -1, -3, -5a y -5b (transductores de señal y activadores de la transcripción) (21,29,31). Posteriormente, las STAT fosforiladas se disocian del receptor y se translocan al núcleo, donde se unen a una secuencias de ADN específicas y activan la transcripción de genes sensibles a GH (figura 1) (19,29).…”
Section: Ghr E Interacción Gh-ghrunclassified