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

ABSTRACT

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.

KEYWORDS:

• Breast cancer
• miR-4728
• MCL1 inhibitor
• apoptosis
• NOXA

Acknowledgements

This work was supported by NCI grant K22CA175276 to ACF and a Mary Kay Foundation grant (ACF).