Funding Source
Department of Defense (DOD)
Grant Number
Department of Defense Award W81XWH-11-1-0105
Department
Department of Chemistry
Document Type
Article
Publication Date
9-2014
Abstract
he human epidermal growth factor receptor 2 (HER2) is a member of the erbB class of tyrosine kinase receptors. These proteins are normally expressed at the surface of healthy cells and play critical roles in the signal transduction cascade in a myriad of biochemical pathways responsible for cell growth and differentiation. However, it is widely known that amplification and subsequent overexpression of the HER2 encoding oncogene results in unregulated cell proliferation in an aggressive form of breast cancer known as HER2-positive breast cancer. Existing therapies such as trastuzumab (Herceptin®) and lapatinib (Tyverb/Tykerb®), a monoclonal antibody inhibitor and a dual EGFR/HER2 kinase inhibitor, respectively, are currently used in the treatment of HER2-positive cancers, although issues with high recurrence and acquired resistance still remain. Small molecule tyrosine kinase inhibitors provide attractive therapeutic targets, as they are able to block cell signaling associated with many of the proposed mechanisms for HER2 resistance. In this regard we aim to present a review on the available HER2 tyrosine kinase inhibitors, as well as those currently in development. The use of tyrosine kinase inhibitors as sequential or combinatorial therapeutic strategies with other HER family inhibitors is also discussed.
Recommended Citation
Molecules 2014, 19, 15196-15212; doi:10.3390/molecules190915196
Included in
Cancer Biology Commons, Medicinal-Pharmaceutical Chemistry Commons, Organic Chemistry Commons
Comments
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).