PMID- 26713679
OWN - NLM
STAT- MEDLINE
DCOM- 20161026
LR  - 20211203
IS  - 1879-016X (Electronic)
IS  - 0163-7258 (Linking)
VI  - 158
DP  - 2016 Feb
TI  - Lymphangioleiomyomatosis: Current understanding and potential treatments.
PG  - 114-24
LID - S0163-7258(15)00234-X [pii]
LID - 10.1016/j.pharmthera.2015.12.008 [doi]
AB  - Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease affecting 
      predominantly young women. Clinical symptoms of this progressive disease include 
      dyspnoea, cough, recurrent pneumothorax, hemoptysis and chylothorax. LAM is 
      generally aggressive in nature and ultimately results in respiratory failure. 
      Important hallmark features of this metastatic disease include the formation of 
      lesions of abnormal smooth muscle cells, cystic destruction of the lung tissue 
      and lymphangiogenesis affecting the lungs, abdomen and lymphatics. Research over 
      the last 10-15 years has significantly enhanced our understanding of the 
      molecular and cellular processes associated with LAM. These processes include 
      mutational inactivation of the tuberous sclerosis complex genes, TSC1 and TSC2, 
      activation of the mammalian target of rapamycin (mTOR) pathway, enhanced cell 
      proliferation and migration, lymphangiogenesis, metastatic spread through the 
      blood and lymphatic circulations, sex steroid sensitivity and dysregulated 
      autophagy. Despite this increased knowledge there is currently no cure for LAM 
      and treatment options remain limited. Whilst the mTOR inhibitor rapamycin has 
      shown some benefit in patients with LAM, with stabilisation of lung function and 
      improved quality of life, cessation of treatment results in recurrence of the 
      disease progression. This highlights the urgent need to identify novel targets 
      and new treatment regimens. The focus of this review is to summarise our current 
      understanding of the cellular and molecular processes associated with LAM and 
      highlight emerging treatments.
CI  - Copyright (c) 2015 Elsevier Inc. All rights reserved.
FAU - Moir, Lyn M
AU  - Moir LM
AD  - Woolcock Institute of Medical Research, The University of Sydney, Sydney, NSW, 
      Australia; Discipline of Pharmacology, Sydney Medical School, The University of 
      Sydney, Sydney, NSW, Australia. Electronic address: lyn.moir@sydney.edu.au.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20151220
PL  - England
TA  - Pharmacol Ther
JT  - Pharmacology & therapeutics
JID - 7905840
RN  - 0 (Antineoplastic Agents)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents/*pharmacology/*therapeutic use
MH  - Humans
MH  - Lung/drug effects/pathology
MH  - Lymphangioleiomyomatosis/*drug therapy/genetics/metabolism/*pathology
MH  - Mutation/genetics
MH  - Quality of Life
MH  - Sirolimus/pharmacology/therapeutic use
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
OTO - NOTNLM
OT  - Hydroxychloroquine
OT  - Lymphangiogenesis
OT  - Rapamycin
OT  - Simvastatin
OT  - Tuberous sclerosis
OT  - Tyrosine kinase inhibitors
EDAT- 2015/12/30 06:00
MHDA- 2016/10/27 06:00
CRDT- 2015/12/30 06:00
PHST- 2015/12/30 06:00 [entrez]
PHST- 2015/12/30 06:00 [pubmed]
PHST- 2016/10/27 06:00 [medline]
AID - S0163-7258(15)00234-X [pii]
AID - 10.1016/j.pharmthera.2015.12.008 [doi]
PST - ppublish
SO  - Pharmacol Ther. 2016 Feb;158:114-24. doi: 10.1016/j.pharmthera.2015.12.008. Epub 
      2015 Dec 20.