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Emerging biomarkers of lymphangioleiomyomatosis
Julie Nijmeh1, Souheil El-Chemaly1, Elizabeth P Henske1
1a Pulmonary and Critical Care Medicine, Department of Medicine , Brigham and Women's Hospital and Harvard Medical School , Boston , MA , USA.
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.
Insights
Lymphangioleiomyomatosis (LAM) research advances include new biomarkers like VEGF-D for diagnosis. Further research is needed for biomarkers to track disease activity and treatment response in LAM patients.
Area of Science:
- Pulmonary Medicine
- Oncology
- Genetics
Background:
- Lymphangioleiomyomatosis (LAM) is a rare, progressive lung disease primarily affecting women, driven by mutations in TSC genes.
- These mutations lead to mTORC1 pathway hyperactivation, a key factor in LAM pathogenesis.
- Recent years have seen significant progress, including VEGF-D identification and sirolimus approval.
Purpose of the Study:
- To review vascular endothelial growth factor D (VEGF-D) as an established LAM biomarker.
- To discuss emerging biomarkers for LAM diagnosis, disease activity, and treatment response.
- To highlight biomarkers with the highest potential impact for LAM patient care.
Main Methods:
- Literature review focusing on VEGF-D and novel LAM biomarkers.
- Analysis of circulating LAM cells, imaging, lipid, and metabolite biomarkers.
- Discussion of research priorities for biomarker development.
Main Results:
- VEGF-D is a validated biomarker aiding LAM diagnosis, potentially obviating lung biopsy.
- Emerging biomarkers show promise for non-invasive diagnosis and monitoring.
- Need for validated biomarkers to predict progression and measure disease activity/burden.
Conclusions:
- VEGF-D has improved LAM diagnosis, but additional biomarkers are crucial.
- Further research is essential for developing non-invasive biomarkers for diagnosis, prognosis, and monitoring.
- Validated biomarkers will enable precision medicine and accelerate clinical trials for LAM.
