Regulation of transforming growth factor-β signaling as a therapeutic approach to treating colorectal cancer

Table 3 Clinical trials of drugs for the treatment of colorectal cancer (United States National Library of Medicine; ClinicalTrials.gov)

Clinical trials (phase)	Drug	Target	Mechanism of action
Antisense oligonucleotides
NCT00844064 (I)	AP12009 (trabedersen)	TGF-β2	By binding to TGF-βII mrna, its expression is reduced
Antibodies
NCT04952753 (II)	NIS793	TGF-β	Reduction of active cytokine, reduction of SMAD2/3 phosphorylation, and reduction of TGF-β target gene expression
NCT02947165 (I)	NIS793	TGF-β	Reduction of active cytokine, reduction of SMAD2/3 phosphorylation, and reduction of TGF-β target gene expression
NCT01646203(I)	IMC-TR1	TGF-βRII	Reduction of active cytokine, reduction of SMAD2/3 phosphorylation, and reduction of TGF-β target gene expression
Ligand traps
NCT03436563 (I/II)	M7824	TGF-βRII	Bifunctional anti-PD-L1/TGF-βRII trap fusion protein
NCT02517398(I)	Bintrafusp alfa	TGF-βRII and PD-L1	First-in-class bifunctional fusion protein composed of a mab against PD-L1 fused to the extracellular domain of the TGF-β receptor II
NCT04856787 (II/III)	SHR-1701	TGF-βRII	Bifunctional anti-PD-L1/TGF-βRII agent
Small molecule receptor kinase inhibitors
NCT04031872 (I/II)	LY3200882; capecitabine	TGF-βRI	By blocking ATP binding to TGF-βR, receptor kinase activity and signal transduction are reduced
NCT05400122 (I)	Vactosertib	TGF-βRI	Inhibits the activity of TGF-βR1
NCT03724851 (I/II)	Vactosertib + Pembroli-zumab	TGF-βRI	Inhibits the activity of TGF-βR1
NCT03470350 (I/II)	Galunisertib	TGF-βRI	Inhibits the activity of TGF-βR1
Immune checkpoints
NCT04540159		TGF-β1	Measuring the level Active TGF-β1 by flow-cytometric analysis in the intraabdominal ascites
Adoptive cell therapy
NCT03431311 (I/II)	ACT	TGF-βII	ACT with Radium-1 TCR + T cells transiently redirected against the TGF-βRII frameshift antigen which is expressed in MSI+ colon cancer.
NCT05040568 (I)	CB-NK-TGF-βR2-/NR3C1		Immunotherapy with ex vivo preactivated and expanded CB-NK cells in combination with cetuximab

ACT: Adoptive cell therapy; TGF: Transforming growth factor.