Emerging biomarkers of lymphangioleiomyomatosis

ABSTRACT

Introduction: Lymphangioleiomyomatosis (LAM) is a destructive lung disease affecting primarily women. LAM is caused by inactivating mutations in the tuberous sclerosis complex (TSC) genes, resulting in hyperactivation of mechanistic/mammalian target of rapamycin complex 1 (mTORC1). Over the past five years, there have been remarkable advances in the diagnosis and therapy of LAM, including the identification of vascular endothelial growth factor D (VEGF-D) as a diagnostic biomarker and the US Food and Drug Administration approval of sirolimus as therapy for LAM. In appropriate clinical situations VEGF-D testing can make lung biopsy unnecessary to diagnose LAM. However, there remains an urgent unmet need for additional biomarkers of disease activity and/or response to therapy.

Areas covered: This work reviews VEGF-D, an established LAM biomarker, and discusses emerging biomarkers, including circulating LAM cells, imaging, lipid, and metabolite biomarkers, focusing on those with the highest potential impact for LAM patients.

Expert commentary: Ongoing research priorities include the development of validated biomarkers to 1) noninvasively diagnose LAM in women whose VEGF-D levels are not diagnostic, 2) accurately predict the likelihood of disease progression and 3) quantitatively measure disease activity and LAM cell burden. These biomarkers would enable personalized, precision clinical care and fast-track clinical trial implementation, with high clinical impact.

KEYWORDS:

• Lymphangioleiomyomatosis
• tuberous sclerosis complex (TSC)
• TSC1
• TSC2
• biomarkers
• VEGF-D
• imaging
• cytokines

Declaration of interest

Work in the Henske and/or El-Chemaly laboratories is supported in part by grants from the National Institutes of Health, the US Department of Defense Tuberous Sclerosis Research Program. The Tuberous Sclerosis Alliance, the LAM Foundation, the Engles Program in TSC and LAM Research, and the Cure for Kathy Fund. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This manuscript has not been funded