Abstract
Lymphangioleiomyomatosis (LAM) is a rare cystic, destructive lung disease occurring almost exclusively in females. Bi-allelic inactivating tuberous sclerosis complex (TSC) gene mutations occur in LAM cells, resulting in activation of the mTORC1 pathway. Pivotal clinical trials have demonstrated that inhibition of mTORC1 with sirolimus can induce a partial response of TSC-associated tumours and decrease the rate of lung function decline in females with LAM. Many parallels have been identified between LAM pathogenesis and neoplasia. Here, we highlight three key nodes through which advances in cancer therapy can streamline future innovation in clinical LAM research with parallels to breast and prostate cancer. These include: 1) hormonally targeted therapies to achieve true disease-free complete remissions; 2) the use of vascular endothelial growth factor-D and other plasma biomarkers to streamline early-phase clinical trials; and 3) the utilisation of histological and molecular features of biopsy material to enable patient stratification and personalised therapies.
Footnotes
Support Statement: S. El-Chemaly was supported by the National Institutes of Health/National Heart, Lung, and Blood Institute (grant no. 1 R21 HL119902). Research in the Henske Lab (Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA) is supported by the LAM Foundation, the Tuberous Sclerosis Alliance, the Department of Defense Tuberous Sclerosis Research Program, the National Heart, Lung, and Blood Institute, the National Institute of Diabetes and Digestive and Kidney Diseases, and the Adler Foundation.
Provenance: Submitted article, peer reviewed.
Statement of Interest: Disclosures can be found alongside the online version of this article at err.ersjournals.com
- Received December 9, 2013.
- Accepted December 20, 2013.
- ©ERS 2014
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