Trastuzumab Resistance: Role for Notch Signaling
Epidermal growth factor receptor-2 (ErbB-2/HER2) is a potent breast oncogene that has been shown to be amplified in 20% of breast cancers. Overexpression of ErbB-2 predicts for aggressive tumor behavior, resistance to some cytotoxic and antihormonal therapies, and poor overall survival. Trastuzumab,...
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| Format: | Article |
| Language: | English |
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Wiley
2009-01-01
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| Series: | The Scientific World Journal |
| Online Access: | http://dx.doi.org/10.1100/tsw.2009.166 |
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| _version_ | 1832550672785997824 |
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| author | Kinnari Mehta Clodia Osipo |
| author_facet | Kinnari Mehta Clodia Osipo |
| author_sort | Kinnari Mehta |
| collection | DOAJ |
| description | Epidermal growth factor receptor-2 (ErbB-2/HER2) is a potent breast oncogene that has been shown to be amplified in 20% of breast cancers. Overexpression of ErbB-2 predicts for aggressive tumor behavior, resistance to some cytotoxic and antihormonal therapies, and poor overall survival. Trastuzumab, the humanized, monoclonal antibody directed against ErbB-2 has shown tremendous efficacy and improved overall survival for women when combined with a taxane-based chemotherapy. However, resistance to trastuzumab remains a major concern, most notably in women with metastatic breast cancer. Numerous mechanisms that include overexpression of alternate receptor tyrosine kinases and/or loss of critical tumor suppressors have been proposed in the last several years to elucidate trastuzumab resistance. Here we review the many possible mechanisms of action that could contribute to resistance, and novel therapies to prevent or reverse the resistant phenotype. Moreover, we provide a critical role for Notch signaling cross-talk with overlapping or new signaling networks in trastuzumab-resistant breast. |
| format | Article |
| id | doaj-art-08cb70a66c814ec9a2135cab8a4b751a |
| institution | Kabale University |
| issn | 1537-744X |
| language | English |
| publishDate | 2009-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | The Scientific World Journal |
| spelling | doaj-art-08cb70a66c814ec9a2135cab8a4b751a2025-02-03T06:05:58ZengWileyThe Scientific World Journal1537-744X2009-01-0191438144810.1100/tsw.2009.166Trastuzumab Resistance: Role for Notch SignalingKinnari Mehta0Clodia Osipo1Molecular Biology Program, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, USAMolecular Biology Program, Cardinal Bernardin Cancer Center, Loyola University Medical Center, Maywood, IL, USAEpidermal growth factor receptor-2 (ErbB-2/HER2) is a potent breast oncogene that has been shown to be amplified in 20% of breast cancers. Overexpression of ErbB-2 predicts for aggressive tumor behavior, resistance to some cytotoxic and antihormonal therapies, and poor overall survival. Trastuzumab, the humanized, monoclonal antibody directed against ErbB-2 has shown tremendous efficacy and improved overall survival for women when combined with a taxane-based chemotherapy. However, resistance to trastuzumab remains a major concern, most notably in women with metastatic breast cancer. Numerous mechanisms that include overexpression of alternate receptor tyrosine kinases and/or loss of critical tumor suppressors have been proposed in the last several years to elucidate trastuzumab resistance. Here we review the many possible mechanisms of action that could contribute to resistance, and novel therapies to prevent or reverse the resistant phenotype. Moreover, we provide a critical role for Notch signaling cross-talk with overlapping or new signaling networks in trastuzumab-resistant breast.http://dx.doi.org/10.1100/tsw.2009.166 |
| spellingShingle | Kinnari Mehta Clodia Osipo Trastuzumab Resistance: Role for Notch Signaling The Scientific World Journal |
| title | Trastuzumab Resistance: Role for Notch Signaling |
| title_full | Trastuzumab Resistance: Role for Notch Signaling |
| title_fullStr | Trastuzumab Resistance: Role for Notch Signaling |
| title_full_unstemmed | Trastuzumab Resistance: Role for Notch Signaling |
| title_short | Trastuzumab Resistance: Role for Notch Signaling |
| title_sort | trastuzumab resistance role for notch signaling |
| url | http://dx.doi.org/10.1100/tsw.2009.166 |
| work_keys_str_mv | AT kinnarimehta trastuzumabresistancerolefornotchsignaling AT clodiaosipo trastuzumabresistancerolefornotchsignaling |