特発性肺線維症と肺がん：メカニズムと分子標的

Idiopathic pulmonary fibrosis and lung cancer: mechanisms and molecular targets

B Ballester, J Milara, J Cortijo - International journal of molecular sciences, 2019 - mdpi.com

… 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 …

Idiopathic Pulmonary Fibrosis and Lung Cancer: Mechanisms and Molecular Targets

Abstract
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.
特発性肺線維症と肺がん：メカニズムと分子標的

概要
特発性肺線維症 (IPF) は、最も一般的な特発性間質性肺疾患であり、診断後の生存期間の中央値は 2~4 年です。かなりの数の IPF 患者が、喫煙歴や付随する肺気腫などの危険因子を持っており、どちらも患者を肺がん (LC) (主に非小細胞肺がん (NSCLC)) にかかりやすくする可能性があります。実際、IPF 自体が LC 発症のリスクを 7% から 20% 増加させます。この点に関して、筋線維芽細胞/間葉転換、筋線維芽細胞の活性化と制御不能な増殖、小胞体ストレス、成長因子発現の変化、酸化ストレス、および大患者が IPF および LC を発症する素因となる可能性がある遺伝的およびエピジェネティックな変異。現在承認されている IPF 療法であるピルフェニドンとニンテダニブも LC で有効です。実際、ニンテダニブは NSCLC の二次治療として承認されており、ピルフェニドンは前臨床試験で抗腫瘍効果を示しています。このレビューでは、新規分子の進歩に基づく現在の IPF および LC-IPF 候補療法だけでなく、IPF 患者の LC の発症に関与するメカニズムに関する現在の知識に焦点を当てています。