Lapatinib is a potent small-molecule inhibitor of the ErbB2 and EGFR tyrosine kinases. In ErbB2 overexpressing breast cancer cell lines, lapatinib unexpectedly activated the antiapoptotic mediator RelA/NF-κB, which was shown to play a functional role in promoting the development of therapeutic resistance to lapatinib. Using immunohistochemical staining, it was found that tumor expression of phosphorylated RelA increased in a subset of ErbB2 overexpressing breast cancer patients who were treated with lapatinib monotherapy, which correlated with a poorer response to therapy. For more details, see article by Xia and colleagues on page 292.