[Current understanding and perspectives of lymphangioleiomyomatosis].

[lymphangioleiomyomatosis]

Lymphangioleiomyomatosis (LAM ) is a slowly progressive neoplastic disease characterized with proliferation of abnormal smooth muscle -like cells (LAM cells ) in the lungs and along axial lymphatics . Proliferation of LAM cells are considered to be driven by dysregulated mTORC 1 signaling , that is caused by mutations in either the TSC 1 or TSC 2 gene in LAM cells . The MILES trial has successfully demonstrated that sirolimus , a mTORC 1 inhibitor , can stabilize pulmonary function in LAM , but its effect disappears once sirolimus is discontinued . Limited ability of sirolimus may be due to concomitant activation of autophagy in LAM cells when mTORC 1 activity is suppressed by sirolimus . Recently animal models for LAM have been independently established by several groups , which may provide a platform for developing drugs interfering various steps in disease progression .