Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acromegaly is an insidious disorder characterized by excess secretion of growth hormone (GH) and elevated circulating levels of insulin-like growth factor-I (IGF-I), generally caused by a pituitary adenoma. It is a rare disease associated with an average 10-year reduction in life expectancy due to metabolic, cardiovascular, and cerebrovascular comorbidities and reduced quality of life caused by paresthesias, fatigue, osteoarthralgia, or bone fractures. In 2000, Cortina Consensus Conference established general criteria for diagnosis and biochemical control of acromegaly, which have been revised in recent years, adapting them to emerging clinical evidences as well as the evolving assay techniques. Authors have proposed a binary definition of cure for acromegaly, where both GH and IGF-I are important determinants: the former is more linked to the presence of residual adenomatous tissue, while the latter to the peripheral activity of the disease. Control of tumor growth and complications is also an essential goal of treatment. Surgical, medical, and radiotherapy approaches are all valid alternatives. The surgical option is, however, unsuccessful in about 50% of patients. Somatostatin analogs (SRLs), octreotide LAR, and lanreotide ATG can inhibit cell growth, besides their beneficial effects on GH hypersecretion and on most comorbidities. Pasireotide is a new multireceptor-targeted SRL with reported superior biochemical efficacy to octreotide, due to higher affinity for SSTR-5, but potentially causing detrimental effects on glucose homeostasis. Pegvisomant could be a valid choice in all patients resistant to SRLs. It is a competitive GH antagonist, which efficaciously blocks IGF-I production, inhibiting the dimerization of GH receptor. Normal IGF-I levels represent, therefore, its only relevant efficacy endpoint, while only few cases of tumor growth on pegvisomant have been reported, so far.
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PMID:The Modern Criteria for Medical Management of Acromegaly. 2694 Mar 87

Despite traditional, multimodality therapy that consisted of surgery, radiotherapy and medical therapies, many patients with acromegaly could not be adequately treated. Pegvisomant is a novel growth hormone receptor antagonist that became available for the treatment of acromegaly in 2003. This drug is a growth hormone variant that has nine mutations to human growth hormone. These give it high affinity for the growth hormone receptor as well as disrupting growth hormone receptor dimerization, with the net effect being antagonism of growth hormone at its receptor. Traditional methods of therapy for acromegaly treat the disease by reducing pituitary tumor secretion of growth hormone and, thus, lowering serum insulin-like growth factor-I levels. Pegvisomant, by contrast, blocks the actions of circulating growth hormone excess, but does not lower serum growth hormone levels. Its efficacy, therefore, is assessed by monitoring serum insulin-like growth factor-I levels. In clinical trials, pegvisomant has been shown to effectively normalize insulin-like growth factor-I levels in up to 97% of patients and to improve acromegaly-related signs and symptoms, and morbidities such as insulin resistance. As the action of pegvisomant does not rely on the tumor's receptor profile, it can be effective even in patients resistant to somatostatin analog therapy. Individually tailored therapy guided by serum insulin-like growth factor-I normalization goals and improvement in clinical signs and symptoms should be undertaken while growth hormone deficiency should be avoided. Pegvisomant is very well tolerated, but liver transaminase levels need to be monitored during therapy. As pegvisomant does not shrink pituitary tumors, the underlying rate of tumor growth may continue on this therapy and periodic pituitary imaging needs to be conducted during therapy.
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PMID:Pegvisomant therapy for acromegaly. 3029 Apr 64