Title |
The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer
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Published in |
BMC Cancer, November 2011
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DOI | 10.1186/1471-2407-11-471 |
Pubmed ID | |
Authors |
Tobias Hahn, Deborah J Bradley-Dunlop, Laurence H Hurley, Daniel Von-Hoff, Stephen Gately, Disis L Mary, Hailing Lu, Manuel L Penichet, David G Besselsen, Brook B Cole, Tanisha Meeuwsen, Edwin Walker, Emmanuel T Akporiaye |
Abstract |
HER2/neu is an oncogene that facilitates neoplastic transformation due to its ability to transduce growth signals in a ligand-independent manner, is over-expressed in 20-30% of human breast cancers correlating with aggressive disease and has been successfully targeted with trastuzumab (Herceptin®). Because trastuzumab alone achieves only a 15-30% response rate, it is now commonly combined with conventional chemotherapeutic drugs. While the combination of trastuzumab plus chemotherapy has greatly improved response rates and increased survival, these conventional chemotherapy drugs are frequently associated with gastrointestinal and cardiac toxicity, bone marrow and immune suppression. These drawbacks necessitate the development of new, less toxic drugs that can be combined with trastuzumab. Recently, we reported that orally administered alpha-tocopheryloxyacetic acid (α-TEA), a novel ether derivative of alpha-tocopherol, dramatically suppressed primary tumor growth and reduced the incidence of lung metastases both in a transplanted and a spontaneous mouse model of breast cancer without discernable toxicity. |
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