common cause of cancer death, causing over 1.5 million deaths per year. A promising direction for new therapies for these and other lung diseases, like asthma,
comes from the notion that deranged intracellular signaling pathways in asthma,
COPD, and lung cancer are critically regulated by protein posttranslational modifications (PTMs). Acetylation and methylation are the quintessential PTMs, found on
over a thousand proteins and influencing a diverse range of protein properties.
Acetyl- and methyltransferases and deacetyl- and demethylases, the enzymes that
control the dynamic process of acetylation and methylation, have consequently been
recognized as important drug targets. Hence, inhibitors of these enzymes have been
developed, which are currently being evaluated in preclinical models of asthma and
COPD and in clinical trials of lung cancer. Significant progress has been made in this
area, with many promising results, but several challenges still need to be overcome
to provide effective new therapies for these airway diseases.
Keywords Asthma, COPD, Deacetylase inhibitors (HDACi), DNA
methyltransferases (DNMTs), Lung cancer, Posttranslational modification (PTM)
Abbreviations
COPD
Chronic obstructive pulmonary disease
DNMT(s) DNA methyltransferase(s)
DNMTi
DNA methyltransferase inhibitor(s)
GR
Glucocorticoid receptor
H3K4
Lysine 4 of histone H3
HDAC(s) Histone deacetylase(s)
HDACi
Histone deacetylase inhibitor(s)
hm5C
5-Hydroxymethylcytosine
IL
Interleukin
KDM(s)
Lysine demethylase(s)
m5C
5-Methylcytosine
NF-κB
Nuclear factor-kappa B
NSCLC
Non-small cell lung cancer
PI3K
Phosphoinositide-3-kinase
PRMT(s) Protein arginine methyltransferase(s)
PTM(s)
Posttranslational modification(s)
SCLC
Small-cell lung cancer
TET
Ten-eleven translocation
TSA
Trichostatin A
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M. R. H. Zwinderman et al.