Lymphangioleiomyomatosis: New Treatment Perspectives

Lung. 2015 Aug;193(4):467-75. doi: 10.1007/s00408-015-9742-6. Epub 2015 May 17.


Lymphangioleiomyomatosis (LAM) is a rare multisystem disease, occurs in women, usually premenopausal, caused by the proliferation of neoplastic smooth muscle-derived cells. Mutations in the tuberous sclerosis complex genes, lead to the activation of mammalian target of rapamycin kinase (mTOR), results in proliferation of LAM cells, its increasing motility, and survival. Polycystic lung destruction, extensive involvement of lymphatic channels, chylothorax, chyloperitoneum, and renal angiomyolipomas can develop in LAM patients. The new, promising treatment strategies have been recently introduced due to discovery of the genetic and molecular mechanisms of LAM. Comprehension of the disease pathogenesis has resulted in the implementation of other therapeutic agents such as mTOR inhibitors, VEGF-D inhibitors, statins, interferon, chloroquine analogs, cyclin-dependent kinase inhibitors, matrix metalloproteinase inhibitors, aromatase inhibitors, and their combinations. The mTOR inhibitors appear to be the most important, and the efficacy of sirolimus in LAM treatment has been proved. The article discussed the new control studies with mTOR inhibitors, doxycycline, simvastatin, and combination of them in LAM patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Autophagy / drug effects
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors
  • Estrogen Antagonists / therapeutic use
  • Female
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Immunotherapy
  • Lymphangioleiomyomatosis / drug therapy*
  • Metalloproteases / antagonists & inhibitors
  • Protein Kinase Inhibitors / therapeutic use*
  • Sex Factors
  • TOR Serine-Threonine Kinases / antagonists & inhibitors
  • Vascular Endothelial Growth Factor D / antagonists & inhibitors


  • Estrogen Antagonists
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Protein Kinase Inhibitors
  • Vascular Endothelial Growth Factor D
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • Cyclin-Dependent Kinase 2
  • Metalloproteases