Epigenetic Enzyme Inhibitors Prevent Resistance to Kinase-Signaling Drugs in Breast Cancer Therapy

Epigenetic Enzyme Inhibitors Prevent Resistance to Kinase-Signaling Drugs in Breast Cancer Therapy
shutterstock_212743078Scientists from University of North Carolina Chapel Hill and North Carolina State University reported that ‘epigenetic enzyme-targeting’ drugs can be utilized to block adaptive kinome reprogramming, which is the primary cause of kinase-signaling drug resistance in breast cancer cell lines. Specifically, resistance to a common breast cancer therapeutic, lapatinib, can be prevented by combinatorial treatment with the BET family bromodomain inhibitor, JQ1. Twenty-five percent of breast cancers are driven by the overexpression of ERBB2, a receptor tyrosine kinase, and inhibition of ERBB2 has been shown to effectively treat breast cancer in a subset of patients. One such inhibitor of ERBB2 is a drug called lapatinib, which acts as an ATP competitor of ERBB2. An unfortunate consequence of utilizing drugs such as lapatinib to target kinase signaling is the subsequent shift in dependence to alternative kinase signaling nodes, termed ‘adaptive kinome reprogramming,’ which compensates for ERBB2 inhibition and results in resistance of tumors to the drug. Furthermore, the ability of tumor cells to circumvent these drugs is not resolved by combinatorial kinase-signaling therapies, as seen with other targeted drug therapies. Researchers hypothesized that by understanding the extent to which adaptive kinome reprogramming triggers resistance to ERBB2 inhibition, a mechanism of prevention of this adaptive response cou
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