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:Idiopathic pulmonary fibrosis (IPF) is a progressive disease of pulmonary scarring. New treatments slow disease progression and allow pulmonary fibrosis patients to live longer. Persistent pulmonary fibrosis increases a patient's risk of developing lung cancer. Lung cancer in patients with IPF differs from cancers that develop in the non-fibrotic lung. Peripherally located adenocarcinoma is the most frequent cell type in smokers who develop lung cancer, while squamous cell carcinoma is the most frequent in pulmonary fibrosis. Increased fibroblast foci in IPF are associated with more aggressive cancer behaviour and shorter doubling times. Treatment of lung cancer in fibrosis is challenging because of the risk of inducing an exacerbation of fibrosis. In order to improve patient outcomes, modifications of current lung cancer screening guidelines in patients with pulmonary fibrosis will be necessary to avoid delays in treatment. 2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography (PET) computed tomography (CT) imaging can help identify cancer earlier and more reliably than CT alone. Increased use of wedge resections, proton therapy and immunotherapy may increase survival by decreasing the risk of exacerbation, but further research will be necessary.
| S-EPMC9973524 | 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:Idiopathic pulmonary fibrosis (IPF) is characterized by progressive, often fatal loss of lung function due to overactive collagen production and tissue scarring. Patients with IPF have a sevenfold-increased risk of developing lung cancer. The COVID-19 pandemic has increased the number of patients with lung diseases, and infection can worsen prognoses for those with chronic lung diseases and disease-associated cancer. Understanding the molecular pathogenesis of IPF-associated lung cancer is imperative for identifying diagnostic biomarkers and targeted therapies that will facilitate prevention of IPF and progression to lung cancer. To understand how IPF-associated fibroblast activation, matrix remodeling, epithelial-to-mesenchymal transition (EMT), and immune modulation influences lung cancer predisposition, we developed a mouse model to recapitulate the molecular pathogenesis of pulmonary fibrosis-associated lung cancer using the bleomycin and Lewis lung carcinoma models. We demonstrate that development of pulmonary fibrosis-associated lung cancer is likely linked to increased abundance of tumor-associated macrophages and a unique gene signature that supports an immune-suppressive microenvironment through secreted factors. Not surprisingly, preexisting fibrosis provides a pre-metastatic niche and results in augmented tumor growth, and tumors associated with bleomycin-induced fibrosis are characterized by a dramatic loss of cytokeratin expression, indicative of EMT.ImplicationsThis characterization of tumors associated with lung diseases provides new therapeutic targets that may aid in the development of treatment paradigms for lung cancer patients with preexisting pulmonary diseases.
| S-EPMC10906012 | 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:BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive fibrosing interstitial lung disease characterised by decline in lung function. We evaluated trajectories of forced vital capacity (FVC) and diffusing capacity (DLco) in a cohort of patients with IPF.MethodsPatients with IPF that was diagnosed or confirmed at the enrolling centre in the previous 6 months were enrolled into the IPF-PRO Registry between June 2014 and October 2018. Patients were followed prospectively, with lung function data collected as part of routine clinical care. Mean trajectories of FVC and DLco % predicted in all patients and in subgroups by characteristics assessed at enrolment were estimated using a joint model that accounted for factors such as disease severity and visit patterns.ResultsOf 1002 patients in the registry, 941 had ≥ 1 FVC and/or DLco measurement after enrolment. The median (Q1, Q3) follow-up period was 35.1 (18.9, 47.2) months. Overall, mean estimated declines in FVC and DLco % predicted were 2.8% and 2.9% per year, respectively. There was no evidence that the mean trajectories of FVC or DLco had a non-linear relationship with time at the population level. Patients who were male, white, had a family history of ILD, were using oxygen, or had prior/current use of antifibrotic therapy at enrolment had greater rates of decline in FVC % predicted. Patients who were male or white had greater rates of decline in DLco % predicted.ConclusionsData from the IPF-PRO Registry suggest a constant rate of decline in lung function over a prolonged period, supporting the inexorably progressive nature of IPF. A graphical abstract summarising the data in this manuscript is available at: https://www.usscicomms.com/respiratory/IPF-PRORegistry_LungFunctionTrajectories .Trial registrationNCT01915511.
| S-EPMC10463468 | biostudies-literature