Promising new treatment targets in patients with fibrosing lung disorders

Table 1 Interstitial lung diseases with a fibro-proliferative pattern, radiologic/histologic phenotypes and new treatment modalities

Etiology	Radiologic/histopathologic phenotype	New treatment modalities studied
Lung-specific involvement
Inhalation of organic antigens (e.g., EAA)	NSIP, UIP, OP, DIP, AIP	No
Inhalation of inorganic materials (e.g., asbestosis)	NSIP, UIP, OP, DIP, AIP	No
Drug and radiation toxicity	NSIP, UIP, OP, DIP, AIP	No
Idiopathic pulmonary fibrosis	UIP ± NSIP	Yes
Idiopathic nonspecific interstitial pneumonia	NSIP ± UIP	No
Systemic involvement
ILDs associated with connective tissue diseases	NSIP, UIP, OP, DIP, AIP	Yes
Sarcoidosis and other granulomatoses	NSIP, UIP, OP, DIP, AIP	Yes

EAA: Extrinsic allergic alveolitis; IPF: Idiopathic pulmonary fibrosis; NSIP: Nonspecific interstitial pneumonia; ILD: Interstitial lung disease; UIP: Usual interstitial pneumonia; OP: Organizing pneumonia; DIP: Desquamative interstitial pneumonia; AIP: Acute interstitial pneumonia.

Table 2 Potential treatment targets in patients with fibrosing lung disease, according to target location

Target	Potential molecular target
Signals from other cells Autocrine signals	Cytokines, survival factors, chemokines, hormones, transmitters, growth factors, extracellular matrix compounds, Wnt, Hedgehog, death factor
Cell surface	Cytokine receptors, receptor tyrosine kinase, G protein-coupled receptors, integrins, Frizzled, Patched, Fas receptor, ion channels
Plasma membrane-cytosol interface	Kinases miRNAs
Cytosol signal transducers	Apoptosis-related proteins
Nucleus	Transcription factors Epigenetic modifiers

miRNA: Micro-ribonucleic acid.

Table 3 Ongoing clinical studies in idiopathic pulmonary fibrosis patients

Target	Potential molecular target	Ongoing clinical study
Signals from other cells	Interleukin 13	Lebrikizumab NCT01872689
Autocrine signals	Connective tissue growth factor	Tralokinumab NCT02036580
		FG-3019 NCT01890265
Cell surface	Lysophosphatidic acid receptor Lysyl oxidase LOXL2 CD20 Androgen receptor	Lysophosphatic acid receptor antagonist-NCT01766817 Simtuzumab NCT01769196 Rituximab NCT01969409 Nandrolone decanoate NCT02055456
Plasma membrane-cytosol interface	Phosphoinositol kinase PI3K	Phosphoinositol kinase PI3K inhibitor NCT01725139
Cytosol signal transducers	Αvβ6 integrin	STX-100 NCT01371305
Nucleus		None
Stem cells		Autologous adipose-derived adult stem cells NCT02135380
		Autologous mesenchymal bone marrow-derived stem cells NCT01919827
		Allogenic human mesenchymal stem cells NCT02013700