Correct!
4. Rapamycin (sirolimus)
Treatment for LAM in the past has included hormonal manipulation with the use of antiestrogens, progesterones and /or oophorectomy, but with variable results (1,2). Lung transplantation has also been performed for LAM, although disease recurrence has been documented. Recently, sirolimus, acting via suppression of mammalian target of rapamycin (mTOR) signaling, has been approved by the FDA for the treatment of LAM. mTOR is a protein kinase that regulates cell growth, cell proliferation, cell motility and cell survival. It also causes an increased expression of VEGF (vascular endothelial growth factor), specifically VEGF-C and VEGF-D. The mTOR causes expression of the metastasis, thus promoting lymphangiogenic vascular endothelial growth factors. VEGF-D serum levels are elevated in 50-70% of patients with LAM. Rapamycin acts to suppress the mTOR, resulting in decreased VEGF levels, hence the mechanism of this treatment. If lung transplant is combined with rapamycin therapy, results may be even more promising. Cladribine is used for pulmonary Langerhans cell histiocytosis (C is incorrect). Corticosteroids can be used to treat lymphoid interstitial pneumonia (D is incorrect). Endothelin receptor antagonists are used for Group I pulmonary arterial hypertension (PAH). PAH may be seen in patients with LAM, but this is classified as a Group V PAH. This is a result of the LAM cells crossing over from the lymphatics in the thoracic duct into the left subclavian vein and ultimately infiltrating the pulmonary microvasculature, resulting in pulmonary hypertension.
References