Lymphangioleiomyomatosis (LAM)

Lymphangioleiomyomatosis (LAM) is a multisystem disease occurring primarily in women that is characterized by lung destruction, renal tumors (angiomyolipomas), and lymphatic involvement. LAM is associated with proliferation of the neoplastic LAM cell, which has mutations/loss of function of the tumor suppressor genes, tuberous sclerosis complex TSC1 or TSC2. Because of the loss of TSC1/TSC2 function, LAM cells exhibit constitutively active mammalian/mechanistic target of rapamycin, with effects on cell proliferation, cell size, autophagy, and other critical biological processes. Rapamycin slows the progression of LAM disease, but appears not to cause LAM cell death. The combination of rapamycin and one (or more) other treatments are being tested for effects on LAM cell migration, invasiveness, and viability.