Chaperone-mediated destruction of erbB2: relevance to tyrosine kinase inhibitors

Excerpt

We are now entering an exciting new era of cancer therapeutics where our goal is to pursue optimal patient outcomes through the use of rationally-designed, target-based anticancer agents. In this light, the four Type 1 erbB plasma membrane-spanning tyrosine kinase receptors (epidermal growth factor receptor [erbB1], erbB2, erbB3 and erbB4), their signal transduction pathways and their inhibition currently comprise the focus of intense research activity. For example, the recent articles by Tan et al. [1], Offterdinger et al. [2], Pusl et al. [3] and Sorkina et al. [4] provide new insights into the effects of erbB2 on the cell cycle, nuclear erbB3, calcium regulation of epidermal growth factor-mediated transcription, and endocytosis of epidermal growth factor receptor respectively. Among these receptors, the erbB2 oncoprotein (HER2/neu) is of particular interest; successes with this molecule have provided proof of principle that targeting of growth factor receptor signalling is a valid therapeutic option in breast cancer. …