PMID- 37914338
OWN - NLM
STAT- MEDLINE
DCOM- 20231107
LR  - 20231107
IS  - 1347-5231 (Electronic)
IS  - 0031-6903 (Linking)
VI  - 143
IP  - 11
DP  - 2023
TI  - [Molecular Mechanism-based Prediction of Interstitial Lung Disease Development 
      Causedby Molecular Targeted Drugs: Association between Signal Transducer and 
      Activator of Transcription 3 and Mammalian Target of Rapamycin inhibitor-induced 
      Interstitial Lung Disease].
PG  - 911-916
LID - 10.1248/yakushi.23-00137 [doi]
AB  - Interstitial lung disease (ILD) is a serious adverse event common to many 
      molecular targeted anticancer drugs. The development of ILD significantly reduces 
      the QOL of patients and results in treatment discontinuation. Because the 
      development of ILD is also associated with therapeutic efficacy, the 
      establishment of prediction strategies for ILD is important. We have focused on 
      signal transducer and activator of transcription 3 (STAT3) as an important 
      mechanistic factor in ILD induced by molecular targeted drugs. Our study aimed to 
      establish mechanism-based ILD prediction strategies; therefore, we investigated 
      the hypothesis that a genetic polymorphism in STAT3 is a predictive factor of the 
      incidence of ILD induced by mammalian target of rapamycin (mTOR) inhibitors, a 
      class of molecular targeted drugs associated with a higher incidence of ILD. Our 
      clinical study clearly demonstrated that the rate of ILD induced by mTOR 
      inhibitors was significantly higher in patients with the G allele homozygous 
      genotype of STAT3 -1697C>G compared with those with other genotypes. The 
      cumulative incidence of ILD in patients with the G allele homozygous genotype was 
      significantly higher compared with that in patients carrying other genotypes. 
      Furthermore, our in vitro study indicated that the epithelial-to-mesenchymal 
      transition (EMT), a pre-process of tissue fibrosis, was induced by an mTOR 
      inhibitor in lung alveolar epithelial cell lines carrying the G allele homozygous 
      genotype which was associated with a higher risk of ILD. Our study provided a 
      novel predictive strategy for the development of ILD induced by molecular 
      targeted drugs.
FAU - Yamamoto, Kazuhiro
AU  - Yamamoto K
AD  - Department of Pharmacy, Kobe University Hospital.
LA  - jpn
PT  - English Abstract
PT  - Journal Article
PL  - Japan
TA  - Yakugaku Zasshi
JT  - Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan
JID - 0413613
RN  - 0 (STAT3 Transcription Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - *Lung Diseases, Interstitial/chemically induced/genetics/epidemiology
MH  - Molecular Targeted Therapy/adverse effects
MH  - Quality of Life
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors
OTO - NOTNLM
OT  - interstitial lung disease
OT  - mammalian target of rapamycin (mTOR)
OT  - molecular targeted drug
OT  - polymorphism
OT  - signal transducer and activator of transcription 3 (STAT3)
EDAT- 2023/11/02 00:43
MHDA- 2023/11/03 06:43
CRDT- 2023/11/01 21:04
PHST- 2023/11/03 06:43 [medline]
PHST- 2023/11/02 00:43 [pubmed]
PHST- 2023/11/01 21:04 [entrez]
AID - 10.1248/yakushi.23-00137 [doi]
PST - ppublish
SO  - Yakugaku Zasshi. 2023;143(11):911-916. doi: 10.1248/yakushi.23-00137.