[Pulmonary lymphangioleiomyomatosis: From pathogenesis to management]

Area of Science:

• Rare disease research
• Pulmonology
• Oncology

Background:

• Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease primarily affecting young women, causing progressive lung destruction.
• LAM involves extrapulmonary manifestations like renal angiomyolipomas and abdominal lymphangioleiomyomas.
• Pathologically, LAM is linked to TSC1/TSC2 gene mutations, activating the mTOR pathway.

Observation:

• The mTOR pathway is a key therapeutic target in LAM.
• mTOR inhibitors (sirolimus, everolimus) benefit some patients by improving lung function and reducing tumor size.
• LAM cells exhibit migratory properties, form new lymphatic vessels, and secrete metalloproteases, contributing to invasiveness.

Findings:

• Mutations in TSC1 and TSC2 genes drive cellular proliferation in LAM.
• Estrogen and progesterone receptors are expressed in LAM cells, suggesting a role for sex hormones.
• Current treatments targeting the mTOR pathway are effective for a subset of patients.

Implications:

• Understanding mTOR-independent mechanisms is crucial for developing novel therapeutic strategies for LAM.
• Further research into sex hormone involvement could offer new treatment avenues.
• Developing new therapies is essential for patients who do not respond to current mTOR inhibitors.