Table 2.

Potential approaches to normalize TGFβ signaling in CF.

Target	Drug Type or Approach
Broad TGFβ pathway inhibition	Monoclonal antibodies targeting ligands or receptors Ligand traps Small molecule inhibitors
TGFβ ligand specific inhibition	Monoclonal antibodies Gene silencing, e. g. siRNAs and antisense oligonucleotides
Smad dependent signaling blockade	Small molecule inhibitors Receptor kinase inhibitors Smad7 upregulation
Non-canonical signaling inhibition	Small molecule inhibitors of relevant pathways, e. g. PI3K and MAPK inhibitors
Pathologic miRNA s	Antagomirs
Modifiers of TGFβ effects:
Co-regulator inhibition	Small molecule inhibitors, antibodies targeting EGFR pathway
Promotion of Th1 inflammatory response	Upregulation of IFN-γ to balance Th2 response driven by TGFβ
Blockade of TGFβ activation	Monoclonal antibodies targeting integrin β6

IFN-γ, interferon gamma; MAPK, mitogen-activated protein kinase; miRNA, microRNA; PI3K, phosphoinositide 3-kinase; siRNA, small interfering RNA