title: Towards personalised therapy for lymphangioleiomyomatosis: lessons from cancer.
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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Dept of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. 2 Both authors contributed equally.
authors.forename: Souheil
authors.initials: S
authors.lastname: El-Chemaly
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Henske
mesh_terms: D001706:Biopsy; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D018192:Lymphangioleiomyomatosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D058990:Molecular Targeted Therapy; D009154:Mutation; D009369:Neoplasms / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics / Q000628:therapy*; D010641:Phenotype; D057285:Precision Medicine; D011237:Predictive Value of Tests; D011379:Prognosis; D018570:Risk Assessment; D012307:Risk Factors