Idiopathic Pulmonary Fibrosis and Lung Cancer: Finding Similarities within Differences.
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ABSTRACT:
SUBMITTER: Reyfman PA
PROVIDER: S-EPMC6890405 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Idiopathic pulmonary fibrosis (IPF) is the most common idiopathic interstitial pulmonary disease with a median survival of 2?4 years after diagnosis. A significant number of IPF patients have risk factors, such as a history of smoking or concomitant emphysema, both of which can predispose the patient to lung cancer (LC) (mostly non-small cell lung cancer (NSCLC)). In fact, IPF itself increases the risk of LC development by 7% to 20%. In this regard, there are multiple common genetic, molecular, and cellular processes that connect lung fibrosis with LC, such as myofibroblast/mesenchymal transition, myofibroblast activation and uncontrolled proliferation, endoplasmic reticulum stress, alterations of growth factors expression, oxidative stress, and large genetic and epigenetic variations that can predispose the patient to develop IPF and LC. The current approved IPF therapies, pirfenidone and nintedanib, are also active in LC. In fact, nintedanib is approved as a second line treatment in NSCLC, and pirfenidone has shown anti-neoplastic effects in preclinical studies. In this review, we focus on the current knowledge on the mechanisms implicated in the development of LC in patients with IPF as well as in current IPF and LC-IPF candidate therapies based on novel molecular advances.
| S-EPMC6387034 | biostudies-literature
Project description:Patients with idiopathic pulmonary fibrosis have a significantly increased risk for the development of lung cancer. The morbidity and mortality of this disease combination are substantial, and, unfortunately, there are currently few data to help guide clinicians in its diagnosis and treatment. In a recent issue of this journal, Hwang et al presented one of the first studies to evaluate lung cancer in patients with idiopathic pulmonary fibrosis at the molecular level. They demonstrate variants in regulators of the cell cycle, which are known to be important in malignant transformation and may also be important in the pathogenesis of idiopathic pulmonary fibrosis. Further understanding of the pathogenic overlap between lung cancer and idiopathic pulmonary fibrosis could help point the direction to specific diagnostic modalities and targeted treatment of both conditions in the future. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
| S-EPMC6491351 | biostudies-literature
Project description:BACKGROUND:There are many epidemiological pieces of evidence that show IPF patients have the highest risk of lung cancer. We conducted a systematic review of all published data to define the characteristics of lung cancer that develops in IPF by performing a meta-analysis. METHOD:This study was performed based on the PRISMA guideline. Documents gathered by searching through the Web of Sciences, Scopus, PubMed/Medline, OVID, and COCHRANE databases which published before 03/25/2018 that related to lung cancer in IPFs' patients. Articles were searched using standard keywords as well as Mesh and Mesh Entry and all probabilistic combinations of words using Boolean operators. Data searching, extracting and quality appraising were done by two researchers, independently. At last, Random-effects size based on Cochrane test and I2 were used. The review protocol has been registered in PROSPERO with ID: CRD42018094037. RESULTS:Based on the meta-analysis conducted in 35 (0.18%) included studies, the total sample size of patients with IPF was estimated 131947 among whom 6384 had LC. The total rate of LC prevalence in IPF patients was estimated to be 13.54% (95% CI: 10.43-17.4) that was significantly 9 times higher in men vs. Women and smoker vs. non-smoker. Highest to lowest prevalence of cellular (histological) subtypes of lung cancer in IPF were SQCC (37.82%), ADC (30.79%), SmCC (20.48%), LCC (5.21%), and ADQC (4.81%), respectively. The highest and lowest stage of lung cancer in IPF patients was estimated at III and II, respectively. The highest involvement location of lung cancer in IPF patients was in the Peripheral. Also, the prevalence of the tumor region involved from the highest to the lowest was estimated to be in the RLL, LLL, RUL and LUL regions. CONCLUSIONS:Lung cancer in IPF, most commonly SQCC, presents in elderly heavy smokers with a male, locating in peripheral regions and the lower part of lung predominance.
| S-EPMC6095562 | biostudies-literature
Project description:The clinical characteristics of lung cancer in patients with idiopathic pulmonary fibrosis (IPF) differ from those of lung cancer in patients without IPF. Thus, we aimed to evaluate the impact of IPF on the clinical course of patients with lung cancer. Clinical data of IPF patients with lung cancer (n = 122) were compared with those of patients with lung cancer without IPF (n = 488) matched by age, sex, histopathology, stage, and date of diagnosis of lung cancer. The median follow-up period after diagnosis of lung cancer was 16 months. Among patients with IPF, the mean age was 68 years, 95.9% were male, 93.2% were ever-smokers, and squamous cell carcinoma was the most common cancer type (48.4%). The IPF group had poorer lung function and lower lobe predominance of lung cancer than the no-IPF group. The IPF group showed a poorer prognosis than the no-IPF group (5-year survival rate: 14.5% vs. 30.1%, respectively; P < 0.001), even after adjusting for lung function and regardless of the treatment method. Among patients with IPF, 16.8% experienced acute exacerbation within 1 month after treatment of lung cancer. The treatment outcome of patients with lung cancer and IPF was generally unfavorable, and acute exacerbation triggered by treatment frequently occurred.
| S-EPMC8050293 | biostudies-literature
Project description:Introduction To investigate the genomic profiles of patients with lung cancer with idiopathic pulmonary fibrosis (IPF-LC), mechanism of carcinogenesis, and potential therapeutic targets. Methods We analyzed 29 matched, surgically resected, cancerous and noncancerous lung tissues (19 IPF-LC and 10 non–IPF-LC) by whole-exome sequencing and bioinformatics analysis and established a medical-engineering collaboration with the Department of Engineering of the Tokyo University of Science. Results In IPF-LC, CADM1 and SPC25 were mutated at a frequency of 47% (9 of 19) and 53% (10 of 19), respectively. Approximately one-third of the IPF-LC cases (7 of 19; 36%) had both mutations. Pathway analysis revealed that these two genes are involved in transforming growth factor-β1 signaling. CADM1 and SPC25 gene mutations decreased the expression of CADM1 and increased that of SPC25 revealing transforming growth factor-β1–induced epithelial-to-mesenchymal transition and cell proliferation in lung cancer cells. Furthermore, treatment with paclitaxel and DNMT1 inhibitor suppressed SPC25 expression. Conclusions CADM1 and SPC25 gene mutations may be novel diagnostic markers and therapeutic targets for IPF-LC.
| S-EPMC8551854 | biostudies-literature
Project description:The risk of lung cancer is higher in idiopathic pulmonary fibrosis (IPF) because both conditions share common risk factors. However, no standard treatment modality for LC in IPF exists due to rare incidence, poor prognosis, and acute exacerbation (AE) of IPF during treatment. We aimed to determine the efficacy of LC treatments and the prognosis in LC patients with IPF according to the LC stage and GAP (gender [G], age [A], and two physiology variables [P]) stage. From 2003 to 2016, 160 retrospectively enrolled patients were classified according to the LC clinical stage and GAP stage. The average (±standard deviation) patient age was 70.1 ± 8.2 years; the cohort predominantly comprised men (94.4%). In GAP stage I, surgery was significantly associated with better survival outcomes in LC. In contrast, no treatment modality yielded significant clinical improvement in GAP stage II/III. The incidences of AE in IPF and its mortality during treatment were 13.8% and 6.3%, respectively. AE occurred commonly in advanced GAP stage. Active treatment should be considered in GAP stage I. The performance status and LC stage should be considered when deciding about the necessity of surgery for patients in advanced GAP stage.
| S-EPMC6715712 | biostudies-literature
Project description:Interstitial lung diseases represent a heterogeneous and wide group of diseases in which factors leading to disease initiation and progression are not fully understood. Recent evidence suggests that the lung microbiome might influence the pathogenesis and progression of interstitial lung diseases. In recent years, the utilization of culture-independent methodologies has allowed the identification of complex and dynamic communities of microbes, in patients with interstitial lung diseases. However, the potential mechanisms by which these changes may drive disease pathogenesis and progression are largely unknown. The aim of this review is to discuss the role of the altered lung microbiome in several interstitial lung diseases. Untangling the host-microbiome interaction in the lung and airway of interstitial lung disease patients is a research priority. Thus, lung dysbiosis is a potentially treatable trait across several interstitial lung diseases, and its proper characterization and treatment might be crucial to change the natural history of these diseases and improve outcomes.
| S-EPMC8779068 | biostudies-literature
Project description:BackgroundNintedanib slows disease progression in patients with Idiopathic Pulmonary Fibrosis (IPF) by reducing decline in Forced Vital Capacity (FVC). The effects of nintedanib on abnormalities on high-resolution computed tomography scans have not been previously studied.ObjectiveWe conducted a Phase IIIb trial to assess the effects of nintedanib on changes in Quantitative Lung Fibrosis (QLF) score and other measures of disease progression in patients with IPF.Methods113 patients were randomized 1:1 to receive nintedanib 150 mg bid or placebo double-blind for ≥6 months, followed by open-label nintedanib. The primary endpoint was the relative change from baseline in QLF score (%) at month 6. Analyses were descriptive and exploratory.ResultsAdjusted mean relative changes from baseline in QLF score at month 6 were 11.4% in the nintedanib group (n=42) and 14.6% in the placebo group (n=45) (difference 3.2% [95% CI: -9.2, 15.6]). Adjusted mean absolute changes from baseline in QLF score at month 6 were 0.98% and 1.33% in these groups, respectively (difference 0.35% [95% CI: -1.27, 1.96]). Adjusted mean absolute changes from baseline in FVC at month 6 were -14.2 mL and -83.2 mL in the nintedanib (n=54) and placebo (n=54) groups, respectively (difference 69.0 mL [95% CI: -8.7, 146.8]).ConclusionExploratory data suggest that in patients with IPF, 6 months' treatment with nintedanib was associated with a numerically smaller degree of fibrotic change in the lungs and reduced FVC decline versus placebo. These data support previous findings that nintedanib slows the progression of IPF.
| S-EPMC7539538 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a progressive chronic disorder characterized by activation of fibroblasts and overproduction of extracellular matrix (ECM). Caveolin-1 (cav-1), a principal component of caveolae, has been implicated in the regulation of numerous signaling pathways and biological processes. We observed marked reduction of cav-1 expression in lung tissues and in primary pulmonary fibroblasts from IPF patients compared with controls. We also demonstrated that cav-1 markedly ameliorated bleomycin (BLM)-induced pulmonary fibrosis, as indicated by histological analysis, hydroxyproline content, and immunoblot analysis. Additionally, transforming growth factor beta1 (TGF-beta1), the well-known profibrotic cytokine, decreased cav-1 expression in human pulmonary fibroblasts. cav-1 was able to suppress TGF-beta1-induced ECM production in cultured fibroblasts through the regulation of the c-Jun N-terminal kinase (JNK) pathway. Interestingly, highly activated JNK was detected in IPF- and BLM-instilled lung tissue samples, which was dramatically suppressed by ad-cav-1 infection. Moreover, JNK1-null fibroblasts showed reduced smad signaling cascades, mimicking the effects of cav-1. This study indicates a pivotal role for cav-1 in ECM regulation and suggests a novel therapeutic target for patients with pulmonary fibrosis.
| S-EPMC1850940 | biostudies-literature
Project description:Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and usually lethal lung disease characterized by unknown causes and few treatment options We used microarray to determine the expression of miRNA and 17 miRNAs were differentially expressed in IPF lungs, including 10 upregulated and 7 downregulated miRNAs. Lung tissue was obtained from 4 IPF patients with histological evidence of usual interstitial pneumonia at the time of surgical lung biopsy or lung transplantation. The diagnosis of IPF was derived according to the standards accepted by the American Thoracic Society/European Respiratory Society. Histological normal lung tissues used as controls was obtained from 3 patients with primary spontaneous pneumothorax at the time of thoracoscopy with stapling of any air leak.The miRNA expression profile was determined by Affymetrix microarray, and transcriptome with Affymetrix array
2015-12-04 | E-GEOD-75647 | biostudies-arrayexpress