Idiopathic pulmonary fibrosis: a disease with similarities and links to cancer biology

Abstract

Several clinical trials have recently targeted specific pathways implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF). However, IPF remains plagued by a median survival of 3 yrs and emphasises the need for further research with new insights and perspectives. The prevailing pathogenic hypotheses assume that either an inflammatory process or an independent epithelial/fibroblastic disorder may propagate the disease process. Based on knowledge developed with considerable scientific evidence, we provide our perspectives with an alternative point of view that IPF be considered as a neoproliferative disorder of the lung. Genetic alterations, response to growth and inhibitory signals, resistance to apoptosis, myofibroblast origin and behaviour, altered cellular communications, and intracellular signalling pathways are all fundamental pathogenic hallmarks of both IPF and cancer. The concept of IPF as a lethal malignant disorder of the lung might extend beyond the pathogenic link between these two diseases and disclose new pathogenic mechanisms leading to novel therapeutic options, adopted from cancer biology. Moreover, this vision might dawn the awareness of the public, political and scientific community of this devastating disease from an angle different from the current perception and provoke new ideas and studies to get a better understanding to control the otherwise relentless progressive disease.

Rapamycin increases CCN2 expression of lung fibroblasts via phosphoinositide 3-kinase

“…To investigate modulatory effects of rapamycin (Sigma, San Francisco, CA, USA) on cell behavior, normal or fibrotic HLFs (N-/F-HLFs) were incubated for different periods of time (1,6,12,24, and 48 h) with rapamycin (5 ng/ml) in the absence or presence of transforming growth factor (TGF)-β1 (10 ng/ml, BD, San Diego, CA, USA). To study the modulatory mechanisms of rapamycin on HLFs, TGF-β type I receptor (TβRI)-and phosphoinositide 3-kinase (PI3K)-specific antagonist (SB431542 and LY294002; 5 and15 μM; Biotrend, Cologne, Germany) was used.…”

“…5 Fibroblasts in the fibrotic lung also have an enhanced motile ability, which is reminiscent that IPF may be a neoproliferative, cancer-like disorder of the lung. 6 However, factors as well as the underlying signaling pathways that regulate CCN2 expression and migration of fibroblasts have not been fully elucidated. Rapamycin (sirolimus) has profound immunosuppressive effects and is currently used for the prevention of graft rejection in organ transplant recipients.…”

Validation of the COPD Assessment Test (CAT) in patients with idiopathic pulmonary fibrosis

“…However, some patients experience an accelerated decline, with acute respiratory worsening and exacerbations [12,13]. It is the type of lung fibrosis with the highest mortality rate, as the median length of survival is 3–5 years [8–11,14], which means that IPF has a poorer prognosis than a number of malignant diseases [7,15]. In 2006, Gribbin and colleagues reported a 43% 5-year survival rate among patients with IPF, and Navaratnam later estimated a 5-year survival rate of 37% in 2011 [4,16].…”

The lived experience with idiopathic pulmonary fibrosis: a qualitative study

“…Median survival is ∼3-5 years from the time of diagnosis [1,2]. The prognosis is worse than for most common malignancies [3]. In Denmark, the incidence of IPF was estimated to 1.3 per 100 000 inhabitants per year in 2003-2009 [4].…”