Extract
Lymphangioleiomyomatosis (LAM) is a slowly progressive, low-grade neoplasm predominantly affecting women that originates from tuberous sclerosis complex (TSC)-deficient cells of mesenchymal lineage (“LAM cells”) in the uterus or pelvis [1, 2]. These LAM cells metastasise through the lymphatics to the abdominal and retroperitoneal lymph nodes, kidneys and lung [1–5]. LAM cells have loss-of-function mutations in both alleles of either TSC1 or TSC2 that function to inhibit the mechanistic target of rapamycin complex 1 (mTORC1). In the absence of tonic inhibition, the mTORC1 pathway is active and drives proliferation and invasion of LAM cells. Drugs such as sirolimus (rapamycin) and everolimus, that inhibit mTORC1, impede LAM cell growth and invasiveness and are clinically effective in slowing the progression of LAM disease [6–8], although this effect is reversible, necessitating continued treatment with medication. There is a subset of patients who progress despite treatment and/or are unable to tolerate the drugs. At present, other than monitoring of lung function tests [9], serum levels of vascular endothelial growth factor D [10], and cyst progression by computed tomography, all of which are lagging indicators of microscopic disease progression, there is no clinically useful way to monitor disease activity/progression and response to therapy.
Abstract
Use of proteinase-specific nanosensors holds great promise to measure lymphangioleiomyomatosis lung disease activity and response to treatment https://bit.ly/3uEsVhF
Footnotes
Conflict of interest: G.P. Downey reports grants from NIH, consulting fees from Angion Biomedica and Roche/Genentech; and is the President Elect, American Thoracic Society (payment made to institution). Y. Aschner reports grants from NIH.
Support statement: Supported by funding from the National Institutes of Health (HL132950 and HL157424 to G.P. Downey), NIH/NCATS Colorado CTSA (KL2 TR002534 and K08HL135279-01A1 to Y. Aschner), and the Parker B. Francis Foundation (Y. Aschner). Funding information for this article has been deposited with the Crossref Funder Registry.
- Received February 23, 2022.
- Accepted March 17, 2022.
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