title: mTOR treatment in lymphangioleiomyomatosis: the role of everolimus.
abstract: The orphan lung disease lymphangioleiomyomatosis (LAM) has until recently been untreatable other than by lung transplantation. However, improved understanding of underlying disease mechanisms has revealed the central role of constitutive up-regulation of the mammalian target of rapamycin (mTOR) pathway in this disease. Although other pathways exist and are under investigation for treatment, several mTOR inhibitors are currently available and emerging information suggests that these may have some efficacy in preventing loss of lung function in LAM. This paper summarizes current understanding of treatment with mTOR inhibitors in LAM, and everolimus in particular. It outlines pharmacokinetics and pharmacodynamics relevant to the clinician, recent clinical studies, and issues with potential side effects. mTOR treatment is not yet available in most countries for LAM, but current data for treatment efficacy are impressive, and it is hoped that mTOR inhibition will soon be recognised as an important treatment of this disease.
authors: a Department of Thoracic Medicine , St Vincent's Hospital , Darlinghurst , NSW , Australia.
authors: Deborah H
authors: DH
authors: Yates
mesh_terms: D003362:Cost-Benefit Analysis; D016527:Drug Costs; D000068338:Everolimus / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006801:Humans; D008168:Lung / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D018192:Lymphangioleiomyomatosis / Q000175:diagnosis / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000191:economics / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D047428:Protein Kinase Inhibitors; D000068338:Everolimus; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases
keywords: Everolimus; lung function; lymphangioleiomyomatosis (LAM); mTOR inhibition; pneumothorax; tuberous sclerosis complex