NODAL and melanoma: NODAL exerts its function by binding to and activating the cell surface receptors ALK4 and ALK7 in cooperation with the co-receptors Cripto-1 (FDGF1) or Cryptic (CFC1) to form a ligand–receptor complex that leads to the phosphorylation of Smad2/3 and the transcription of target genes, including NODAL itself.73 The only available inhibitor of NODAL to date, monoclonal anti-NODAL antibody 3D1,80,81 has demonstrated success in preclinical models of melanoma and is currently undergoing further preclinical evaluation.