Abstract
Lymphangioleiomyomatosis (LAM) is a rare multisystemic disease primarily affecting women, manifested as cystic lung destruction, angiomyolipomas (AMLs) and lymphagioleiomyomas. The hallmark of LAM is the presence of abnormal perivascular epithelioid cells, referred to as LAM cells. LAM is classified into tuberous sclerosis-associated (TSC) and sporadic forms according to the presence or absence of TSC gene mutations. In recent decades, the benefit of mechanistic target of rapamycin (mTOR) inhibitors has been demonstrated in stabilising respiratory function, reducing AMLs, lymphangioleiomyoma and chylous effusions, and controlling TSC-associated seizures. In addition to mTOR inhibition, clinical trials have explored therapies targeting autophagy, receptors of tyrosine kinases (RTKs), nonreceptor tyrosine kinases (non-RTKs) and hormones. More recently, new treatments avenues involving immune microenvironment, histamine signalling and Src kinase inhibition have entered pre-clinical and/or clinical evaluation. This review summarises the multiple pathophysiological mechanisms in LAM and highlights the therapeutic targets identified to date. Several clinical trials have been described, offering insights into their potential application and further research.