Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer
The 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 gr...
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| Format: | Article |
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MDPI AG
2014-09-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/19/9/15196 |
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| author | Richard L. Schroeder Cheryl L. Stevens Jayalakshmi Sridhar |
| author_facet | Richard L. Schroeder Cheryl L. Stevens Jayalakshmi Sridhar |
| author_sort | Richard L. Schroeder |
| collection | DOAJ |
| description | The 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. |
| first_indexed | 2024-12-23T11:11:06Z |
| format | Article |
| id | doaj.art-1baf3ca7f2444328bf028df592645685 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T11:11:06Z |
| publishDate | 2014-09-01 |
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| series | Molecules |
| spelling | doaj.art-1baf3ca7f2444328bf028df5926456852022-12-21T17:49:21ZengMDPI AGMolecules1420-30492014-09-01199151961521210.3390/molecules190915196molecules190915196Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast CancerRichard L. Schroeder0Cheryl L. Stevens1Jayalakshmi Sridhar2Department of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USAOgden College of Science and Engineering, Western Kentucky University, 1906 College Heights Boulevard #11075, Bowling Green, KY 42101, USADepartment of Chemistry, Xavier University of Louisiana, 1 Drexel Drive, New Orleans, LA 70125, USAThe 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.http://www.mdpi.com/1420-3049/19/9/15196human epidermal growth factor 2 (HER2)kinase domainHER2 inhibitionmonoclonal antibodiessmall molecule inhibitors |
| spellingShingle | Richard L. Schroeder Cheryl L. Stevens Jayalakshmi Sridhar Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer Molecules human epidermal growth factor 2 (HER2) kinase domain HER2 inhibition monoclonal antibodies small molecule inhibitors |
| title | Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer |
| title_full | Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer |
| title_fullStr | Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer |
| title_full_unstemmed | Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer |
| title_short | Small Molecule Tyrosine Kinase Inhibitors of ErbB2/HER2/Neu in the Treatment of Aggressive Breast Cancer |
| title_sort | small molecule tyrosine kinase inhibitors of erbb2 her2 neu in the treatment of aggressive breast cancer |
| topic | human epidermal growth factor 2 (HER2) kinase domain HER2 inhibition monoclonal antibodies small molecule inhibitors |
| url | http://www.mdpi.com/1420-3049/19/9/15196 |
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