Treatment Option(s) for Pulmonary Lymphangioleiomyomatosis: Progress and Current Challenges

Krymskaya, Vera P.

doi:10.1165/rcmb.2011-0381ed

Cited by 8 publications

(9 citation statements)

References 39 publications

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“…Lymphangioleiomyomatosis (LAM) is a progressive pulmonary disease which affects almost exclusively women. LAM is characterized pathologically by widespread proliferation of abnormal smooth muscle cells, which typically have the tuberous sclerosis complex 2 ( TSC2 ) mutation leading to mTORC1 activation, and by cystic changes within the lung parenchyma (McCormack et al, 2010, 2012; Taveira-DaSilva et al, 2010; Henske and McCormack, 2012; Krymskaya, 2012). LAM occurs in 30–40% of women with TSC (Costello et al, 2000; Dabora et al, 2001).…”

mentioning

confidence: 99%

Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells

Lee

Sun

et al. 2014

Journal of Experimental Medicine

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confidence: 99%

Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells

Lee

Sun

et al. 2014

Journal of Experimental Medicine

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“…LAM is a predominantly female lung manifestation characterized by the accumulation of abnormal smooth muscle cells in the lung parenchyma and severe emphysema-like lung destruction that can lead to respiratory failure and mortality (10,(30)(31)(32). The marked gender specificity of LAM suggests that circulating female hormones including estrogen promote disease progression.…”

Section: Discussionmentioning

confidence: 99%

Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis

Zhang

et al. 2016

JCI Insight

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“…Clinical studies suggest that therapeutic use of sirolimus and everolimus might require life-long treatment (although this have to be clinically proven) because drug withdrawal results in further disease progression [5, 27, 28]. Why did mTOR inhibitors sirolimus and everolimus fail to have a long-lasting effect in LAM?…”

Section: Therapeutic Strategies To Eradicate Lam Cellsmentioning

confidence: 99%

Therapeutic strategies for treatment of pulmonary lymphangioleiomyomatosis

Krymskaya

2014

Expert Opinion on Orphan Drugs

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Introduction Pulmonary lymphangioleiomyomatosis (LAM) is a rare progressive lung disease affecting almost exclusively women. Neoplastic growth of atypical smooth muscle-like cells in the lung induces destruction of lung parenchyma leading to the formation of lung cysts, rupture of which results in spontaneous pneumothorax. LAM occurs sporadically or in association with inherited hamartoma syndrome tuberous sclerosis complex (TSC). Progression of LAM often results in loss of pulmonary function and death. Increasing understanding of neoplastic LAM cell growth is driving the development of therapeutic approaches targeting the disease progression. Areas covered This review provides background to understand the rationale for current treatments used in patients with LAM, to critically appraise the evidence for these treatments, and to discuss future treatment approaches. The literature review includes publications from PubMed and clinicaltrials.gov/. Expert Opinion Targeting mTOR activation with rapamycin analogs sirolimus and everolimus are awaiting approval by the FDA for treatment of LAM. A number of other treatment options have been investigated and are currently tested in clinical trials to target LAM cell survival and metastasis. Key remaining and poorly understood areas for development and validation of therapeutic targeting in LAM are destruction of lungs, pathological lymphangiogenesis, and hormonal regulation. Future will reveal whether they could be targeted therapeutically.

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Treatment Option(s) for Pulmonary Lymphangioleiomyomatosis: Progress and Current Challenges

Cited by 8 publications

References 39 publications

Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells

Estradiol and mTORC2 cooperate to enhance prostaglandin biosynthesis and tumorigenesis in TSC2-deficient LAM cells

Proapoptotic protein Bim attenuates estrogen-enhanced survival in lymphangioleiomyomatosis

Therapeutic strategies for treatment of pulmonary lymphangioleiomyomatosis

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