Figure 2.

This figure highlights the vicious cycle of bone metastasis driven by TGFβ signaling, emphasizing the potential for therapeutic intervention in this pathway to disrupt the cycle of bone destruction and tumor growth promotion. Several approaches can be used to target this pathway. (1) TGFβ ligands are neutralized or trapped using soluble decoy receptors or neutralizing antibodies; (2) TGFβ receptor kinase inhibitors, like SD-208 and LY2109761, act via ATP-competitive inhibition; (3) using antisense oligonucleotides (ASO), such as Ap-12009 (trabedersen), offers another strategy to reduce TGFβ levels by inhibiting mRNA function and protein synthesis; (4) biologic-based molecules like BMP7 counteract TGFβ-induced epithelial–mesenchymal transition and inhibit the formation of bone metastases.