PMID- 33466795
OWN - NLM
STAT- MEDLINE
DCOM- 20210412
LR  - 20220716
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 2
DP  - 2021 Jan 14
TI  - Molecular and Clinical Features of EGFR-TKI-Associated Lung Injury.
LID - 10.3390/ijms22020792 [doi]
LID - 792
AB  - The tyrosine kinase activity of epidermal growth factor receptors (EGFRs) plays 
      critical roles in cell proliferation, regeneration, tumorigenesis, and anticancer 
      resistance. Non-small-cell lung cancer patients who responded to EGFR-tyrosine 
      kinase inhibitors (EGFR-TKIs) and obtained survival benefits had somatic EGFR 
      mutations. EGFR-TKI-related adverse events (AEs) are usually tolerable and 
      manageable, although serious AEs, including lung injury (specifically, 
      interstitial lung disease (ILD), causing 58% of EGFR-TKI treatment-related 
      deaths), occur infrequently. The etiopathogenesis of EGFR-TKI-induced ILD remains 
      unknown. Risk factors, such as tobacco exposure, pre-existing lung fibrosis, 
      chronic obstructive pulmonary disease, and poor performance status, indicate that 
      lung inflammatory circumstances may worsen with EGFR-TKI treatment because of 
      impaired epithelial healing of lung injuries. There is limited evidence from 
      preclinical and clinical studies of the mechanisms underlying EGFR-TKI-induced 
      ILD in the available literature. Herein, we evaluated the relationship between 
      EGFR-TKIs and AEs, especially ILD. Recent reports on mechanisms inducing lung 
      injury or resistance in cytokine-rich circumstances were reviewed. We discussed 
      the relevance of cytotoxic agents or immunotherapeutic agents in combination with 
      EGFR-TKIs as a potential mechanism of EGFR-TKI-related lung injury and reviewed 
      recent developments in diagnostics and therapeutics that facilitate recovery from 
      lung injury or overcoming resistance to anti-EGFR treatment.
FAU - Ohmori, Tohru
AU  - Ohmori T
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
FAU - Yamaoka, Toshimitsu
AU  - Yamaoka T
AUID- ORCID: 0000-0002-6182-6047
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
AD  - Advanced Cancer Translational Research Institute, Showa University, 1-5-8 
      Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan.
FAU - Ando, Koichi
AU  - Ando K
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
FAU - Kusumoto, Sojiro
AU  - Kusumoto S
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
FAU - Kishino, Yasunari
AU  - Kishino Y
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
FAU - Manabe, Ryou
AU  - Manabe R
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
FAU - Sagara, Hironori
AU  - Sagara H
AUID- ORCID: 0000-0003-2376-1606
AD  - Department of Medicine, Division of Respiratory Medicine and Allergology, Showa 
      University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, 
      Japan.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20210114
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Acrylamides)
RN  - 0 (Aniline Compounds)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 3C06JJ0Z2O (osimertinib)
RN  - 41UD74L59M (Afatinib)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Acrylamides/adverse effects/therapeutic use
MH  - Afatinib/adverse effects/therapeutic use
MH  - Aniline Compounds/adverse effects/therapeutic use
MH  - Carcinoma, Non-Small-Cell Lung/*drug therapy/genetics
MH  - ErbB Receptors/*antagonists & inhibitors/genetics
MH  - Gefitinib/adverse effects/therapeutic use
MH  - Humans
MH  - Lung Diseases, Interstitial/chemically induced/*diagnosis
MH  - Lung Injury/chemically induced/*diagnosis
MH  - Lung Neoplasms/*drug therapy/genetics
MH  - Mutation
MH  - Protein Kinase Inhibitors/*adverse effects/therapeutic use
PMC - PMC7829873
OTO - NOTNLM
OT  - EGFR-TKIs
OT  - TNF
OT  - inflammation
OT  - lung injury
COIS- The authors declare no conflict of interest. The funding sponsors had no role in 
      the choice of research project; design of the study; in the collection, analyses 
      or interpretation of data; in the writing of the manuscript; or in the decision 
      to publish the results.
EDAT- 2021/01/21 06:00
MHDA- 2021/04/13 06:00
PMCR- 2021/01/14
CRDT- 2021/01/20 01:07
PHST- 2020/12/23 00:00 [received]
PHST- 2021/01/12 00:00 [revised]
PHST- 2021/01/12 00:00 [accepted]
PHST- 2021/01/20 01:07 [entrez]
PHST- 2021/01/21 06:00 [pubmed]
PHST- 2021/04/13 06:00 [medline]
PHST- 2021/01/14 00:00 [pmc-release]
AID - ijms22020792 [pii]
AID - ijms-22-00792 [pii]
AID - 10.3390/ijms22020792 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jan 14;22(2):792. doi: 10.3390/ijms22020792.