Enzyme Assay Development for Hormonally Up-regulated Neu-associated Kinase (HUNK) Protein: A Target in EGFR+ (HER2+/ErbB2+) Breast Cancers

Abstract

Background: Breast cancer is the second lead­ing cause of cancer death among women in the United States, with about 264,000 cases of breast cancer diagnoses and 42,000 deaths per year. For many drug-resistant metastatic breast cancers, epidermal growth factor receptor (EGFR) is highly expressed with a conferred re­sistance to HER2/ErbB2 inhibitors. Hormonally up-regulated protein kinase (HUNK) is a pro­tein kinase that has been evidenced as a target in EGFR+ (HER2+/ErbB2+) breast cancers, pre­senting a potential for targeted treatment.

Methods: To determine its efficacy as a target, we implemented ADP enzyme assays to test the amount of phosphorylation of HUNK, both alone and in the presence of various HUNK inhibitors.

Results: The activity of specific drug inhibitors was found to be inconclusive. However, HUNK does demonstrate affinity to EGFR when com­bined with additional DTT, suggesting its po­tential for further study as a target for drug-resis­tant breast cancer therapy.