One gene to rule them all…and in the darkness bind them.

Pharmaceutical inhibition of the Human Epidermal growth factor Receptor 2 (HER2) oncogene has dramatically improved outcomes in HER2-amplified breast cancers. However, monotherapy HER2 inhibitors are not effective. We have recently reported that a co-amplified microRNA within the HER2 amplicon, leads to activation of the oncogene Myeloid Cell Leukemia-1 (MCL-1), tempering cell death responses to HER2 inhibitors. Importantly, HER2 inhibitors are sensitized to cell death by the addition of pharmacological MCL-1 inhibitors, which are entering clinical trials.