Integrated research for clarification of molecular biological and pharmacogenomic mechanisms of interstitial lung disease induced by molecular targeted drugs

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K08401
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Kobe University
• Principal Investigator: Yamamoto Kazuhiro 神戸大学, 医学部附属病院, 特命講師 (30610349)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 間質性肺疾患 / mTOR阻害薬 / STAT3 / EMT

Outline of Final Research Achievements

In this study, we clarify that the patients with CC genotype of STAT3 single nucleotide polymorphism (SNP) rs4796793 have a higher risk of interstitial lung disease induced by mammalian target of rapamycin (mTOR) inhibitor. Moreover, we observed that expression or activity of EMT marker and EMT related signal transduction factor is different from genotype of rs4796793 in human lung cancer cell lines.
Our study suggest that mechanism of molecular targeted drugs-induced interstitial lung disease associate with STAT3. To acumulate the data by further experiments, it is expected that STAT3 polymorphism use as the prediction marker of interstitial lung disease.

Free Research Field

ゲノム薬理学

Academic Significance and Societal Importance of the Research Achievements

間質性肺疾患はときに致命的な病態となる重大な副作用であり、近年の分子標的型薬剤の開発促進により、その発症者は経年的に増加している。これまで解明されていなかった分子標的治療薬に起因する間質性肺疾患の発症メカニズムにSTAT3と呼ばれるシグナル因子が関連することを明らかにすることができれば、これらのメカニズムに基づく発症予測因子や新規予防・治療方法の確立が期待される。