Antibodies targeting individual Notch receptors (151, 152) seem to avoid toxicity but, in some situations, tumors may have high levels of more than one receptor (e.g., Notch1 and Notch2 in CLL, Notch1 and Notch4 in breast CSCs), or potentially, the roles of individual Notch receptors may contribute differently in the tumor versus its microenvironment, which adds further complications. This evidence concerns the gene NOTCH4 and neoplasm.