Issues

Photomicrograph of MDA-MB-134-VI triple-negative breast cancer (TNBC) cells stained for senescence-associated β-galactosidase activity. Diamond and colleagues investigated the efficacy of the Aurora and angiogenic kinase inhibitor ENMD-2076 against preclinical models of breast cancer and showed robust activity in TNBC models, an area of unmet need. MDA-MB-134-VI cells showed inherent resistance to ENMD-2076, which was associated with markers of cellular senescence such as increased β-galactosidase activity and cell size. These investigators further showed that TNBC cell lines with mutant p53 and increased p53 protein expression were more sensitive to the proapoptotic effects of ENMD-2076 than mutant p53 cell lines that showed decreased p53 expression. These phenotypic differences could serve as predictive biomarkers of response to ENMD-2076 and other Aurora kinase inhibitors, which may prove useful in selecting TNBC patients for future clinical trials. For details, see the article by Diamond and colleagues on page 291 of this issue.