Comprehensive lung injury pathology induced by mTOR inhibitors

  title={Comprehensive lung injury pathology induced by mTOR inhibitors},
  author={Guadalupe L. Aparicio and Mois{\'e}s Blanco Calvo and Vanessa Medina and Ovidio Fern{\'a}ndez and Paula Jim{\'e}nez and Martina Lema and Ang{\'e}lica Figueroa and Luis Miguel Ant{\'o}n Aparicio},
  journal={Clinical and Translational Oncology},
Interstitial lung disease is a rare side effect of temsirolimus treatment in renal cancer patients. Pulmonary fibrosis is characterised by the accumulation of extracellular matrix collagen, fibroblast proliferation and migration, and loss of alveolar gas exchange units. Previous studies of pulmonary fibrosis have mainly focused on the fibro-proliferative process in the lungs. However, the molecular mechanism by which sirolimus promotes lung fibrosis remains elusive. Here, we propose an overall… 

High dose everolimus promotes a pro-inflammatory phenotype and facilitates the epithelial to mesenchymal transition of primary bronchial epithelial cells isolated from cystic fibrosis patients.

It is demonstrated that high dose EVE may trigger a pro-inflammatory/fibrotic biological machinery in bronchial epithelial cells from CF patients, and solid organ transplant recipients affected by CF should be treated with the lowest possible dose of mTOR inhibitors to minimize/avoid the onset and development of lung complications.

Drug-Induced Lung Injury

This book covers various aspects of a respiratory system disorder associated with prescribed drugs that do not yet have established treatment guidelines, and for which the only treatment is to

Drug-induced pneumonitis in cancer patients treated with mTOR inhibitors: management and insights into possible mechanisms

Current understanding of the mechanism of DIP, as well as the clinical impact and management of this toxicity in cancer patients treated with mTOR inhibitors, are reviewed.

The mechanism of rapamycin in the intervention of paraquat-induced acute lung injury in rats

The analyses showed that application of rapamycin could significantly reduce the lung injury damage caused by PQ, with lung tissue wet–dry weight ratio, pathological features, compositions in serum, protein in bronchoalveolar lavage fluid and other indices being significantly improved after the injection ofRapamycin.

Aspergillosis Superinfection as a Cause of Death of Crizotinib-Induced Interstitial Lung Disease Successfully Treated with High-Dose Corticosteroid Therapy

The experience suggests that high-dose steroid therapy may be efficacious in the management of a severe complication of crizotinib therapy, however, potent antifungal therapy should be considered to prevent the risk of severe aspergillosis.

Emerging Perspectives on mTOR Inhibitor-Associated Pneumonitis in Breast Cancer.

An overview of mTOR inhibitor-associated pneumonitis is provided, with a focus on the detection, accurate diagnosis, and optimal management of this class-related complication of m TOR inhibitor therapy.

Imaging Features of Drug-Induced Interstitial Lung Disease: How HRCT of DLI Is Interpreted

Since imaging finding of drug-induced lung injury (DLI) is varying and nonspecific, diagnosis of DLI must be performed by the integration of clinical, imaging, and pathologic findings, when

Pazopanib in the treatment of renal cell carcinoma

This review will focus on pazopanib’s in vitro activity, clinical effectiveness, side-effect profile and how it can be integrated among the other available drugs in the management of RCC.

Independent Mechanism − β by a TGF-Genetic and Pharmacologic Inhibition of mTORC 1 Promotes EMT

It is reported here that inhibition of either mTOR or RPTOR triggers EMT in mammary epithelial cells, and results suggest a plausible etiologic explanation for the progressive pulmonary fibrosis, a frequent adverse condition associated with the therapeutic use of mTOR inhibitors.

Genetic and pharmacologic inhibition of mTORC1 promotes EMT by a TGF-β-independent mechanism.

It is reported here that inhibition of either mTOR or RPTOR triggers EMT in mammary epithelial cells, and results suggest a plausible etiologic explanation for the progressive pulmonary fibrosis, a frequent adverse condition associated with the therapeutic use of mTOR inhibitors.



Targeting genes for treatment in idiopathic pulmonary fibrosis: challenges and opportunities, promises and pitfalls.

Inflammation is a critical element of the initiation of fibrosis and data indicate that the Smad pathway is a necessary link to fibrosis through TGF-beta and Smad3 signaling, which introduces matrix regulation as a new target for therapeutic intervention.

Characterisation of the lung toxicity of the cell cycle inhibitor temsirolimus.

Increased production of the potent oxidant peroxynitrite in the lungs of patients with idiopathic pulmonary fibrosis.

The production of nitrotyrosine, a byproduct of protein nitration by peroxynitrite, and the expression of the enzymes responsible for generating NO, in lungs of patients with IPF and compared them with lungs of normal control subjects is investigated.

The pathogenesis of bleomycin-induced pulmonary fibrosis in mice.

The consistent induction of changes similar to those of diffuse pulmonary fibrosis or fibrosing alveolitis in man suggests that bleomycin-induced injury may provide a suitable model for the investigation of this ill-defined group of diseases.

Bleomycin increases superoxide anion generation by pig peripheral alveolar macrophages.

Results from this study suggest that an excess production of superoxide anions by alveolar macrophages may be the underlying cause of bleomycin pulmonary toxicity.


The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship.

Poly(ADP-ribosyl)ation in asthma and other lung diseases.

Drug-induced lung disease: 1990 review.

The possibility of an iatrogenic manifestation should always be considered in patients developing pulmonary symptoms, and data from biological investigations, although not specific, contribute to the understanding of lung injury mechanisms.

iNOS gene upregulation is associated with the early proliferative response of human lung fibroblasts to cytokine stimulation

The hypothesis that NO is involved in the activation of pulmonary fibroblasts and upregulation of the iNOS gene is an early event in the proliferative response of human lung fibro Blasts to inflammatory stimuli is supported.

Transforming growth factor beta 1 is present at sites of extracellular matrix gene expression in human pulmonary fibrosis.

The presence of transforming growth factor beta 1 (TGF-beta 1), a potent profibrotic cytokine, in the foci containing activated fibroblasts suggests that matrix-associated TGF- beta 1 may serve as a stimulus for the persistent expression of connective tissue genes.