The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer

Persistent Link:
http://hdl.handle.net/10150/610346
Title:
The vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast cancer
Author:
Hahn, Tobias; Bradley-Dunlop, Deborah; Hurley, Laurence; Von-Hoff, Daniel; Gately, Stephen; Mary, Disis; Lu, Hailing; Penichet, Manuel; Besselsen, David; Cole, Brook; Meeuwsen, Tanisha; Walker, Edwin; Akporiaye, Emmanuel
Affiliation:
Earle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR, 97213, USA; Department of Immunobiology, The University of Arizona, Tucson, AZ, 85724, USA; Department of Pharmacy, The University of Arizona, Tucson, AZ, 85724, USA; The Arizona Cancer Center, The University of Arizona, Tucson, AZ, 85724, USA; Translational Genomics Research Institute, Phoenix, AZ, 857004, USA; School of Medicine, The University of Washington, Seattle, WA, 98195, USA; Division of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA, 90095, USA; Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USA; The Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USA; Jonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, 90095, USA; Department of Veterinary Science and Microbiology, The University of Arizona, Tucson, AZ, 85721, USA
Issue Date:
2011
Publisher:
BioMed Central
Citation:
Hahn et al. BMC Cancer 2011, 11:471 http://www.biomedcentral.com/1471-2407/11/471
Journal:
BMC Cancer
Rights:
© 2011 Hahn et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)
Collection Information:
This item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.
Abstract:
BACKGROUND: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(R)). 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 (alpha-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.METHODS:In this study we examined the effect of alpha-TEA plus HER2/neu-specific antibody treatment on HER2/neu-expressing breast cancer cells in vitro and in a HER2/neu positive human xenograft tumor model in vivo.RESULTS:We show in vitro that alpha-TEA plus anti-HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor cells and human breast cancer cells and that the anti-tumor effect of alpha-TEA is independent of HER2/neu status. More importantly, in a human breast cancer xenograft model, the combination of alpha-TEA plus trastuzumab resulted in faster tumor regression and more tumor-free animals than trastuzumab alone.CONCLUSION:Due to the cancer cell selectivity of alpha-TEA, and because alpha-TEA kills both HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential to be effective and less toxic than existing chemotherapeutic drugs when used in combination with HER2/neu antibody.
EISSN:
 1471-2407
DOI:
10.1186/1471-2407-11-471
Version:
Final published version
Additional Links:
http://www.biomedcentral.com/1471-2407/11/471

Full metadata record

DC FieldValue Language
dc.contributor.authorHahn, Tobiasen
dc.contributor.authorBradley-Dunlop, Deborahen
dc.contributor.authorHurley, Laurenceen
dc.contributor.authorVon-Hoff, Danielen
dc.contributor.authorGately, Stephenen
dc.contributor.authorMary, Disisen
dc.contributor.authorLu, Hailingen
dc.contributor.authorPenichet, Manuelen
dc.contributor.authorBesselsen, Daviden
dc.contributor.authorCole, Brooken
dc.contributor.authorMeeuwsen, Tanishaen
dc.contributor.authorWalker, Edwinen
dc.contributor.authorAkporiaye, Emmanuelen
dc.date.accessioned2016-05-20T09:04:46Z-
dc.date.available2016-05-20T09:04:46Z-
dc.date.issued2011en
dc.identifier.citationHahn et al. BMC Cancer 2011, 11:471 http://www.biomedcentral.com/1471-2407/11/471en
dc.identifier.doi10.1186/1471-2407-11-471en
dc.identifier.urihttp://hdl.handle.net/10150/610346-
dc.description.abstractBACKGROUND: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(R)). 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 (alpha-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.METHODS:In this study we examined the effect of alpha-TEA plus HER2/neu-specific antibody treatment on HER2/neu-expressing breast cancer cells in vitro and in a HER2/neu positive human xenograft tumor model in vivo.RESULTS:We show in vitro that alpha-TEA plus anti-HER2/neu antibody has an increased cytotoxic effect against murine mammary tumor cells and human breast cancer cells and that the anti-tumor effect of alpha-TEA is independent of HER2/neu status. More importantly, in a human breast cancer xenograft model, the combination of alpha-TEA plus trastuzumab resulted in faster tumor regression and more tumor-free animals than trastuzumab alone.CONCLUSION:Due to the cancer cell selectivity of alpha-TEA, and because alpha-TEA kills both HER2/neu positive and HER2/neu negative breast cancer cells, it has the potential to be effective and less toxic than existing chemotherapeutic drugs when used in combination with HER2/neu antibody.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.relation.urlhttp://www.biomedcentral.com/1471-2407/11/471en
dc.rights© 2011 Hahn et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0)en
dc.titleThe vitamin E analog, alpha-tocopheryloxyacetic acid enhances the anti-tumor activity of trastuzumab against HER2/neu-expressing breast canceren
dc.typeArticleen
dc.identifier.eissn 1471-2407en
dc.contributor.departmentEarle A. Chiles Research Institute, Robert W. Franz Cancer Research Center, Providence Portland Medical Center, Portland, OR, 97213, USAen
dc.contributor.departmentDepartment of Immunobiology, The University of Arizona, Tucson, AZ, 85724, USAen
dc.contributor.departmentDepartment of Pharmacy, The University of Arizona, Tucson, AZ, 85724, USAen
dc.contributor.departmentThe Arizona Cancer Center, The University of Arizona, Tucson, AZ, 85724, USAen
dc.contributor.departmentTranslational Genomics Research Institute, Phoenix, AZ, 857004, USAen
dc.contributor.departmentSchool of Medicine, The University of Washington, Seattle, WA, 98195, USAen
dc.contributor.departmentDivision of Surgical Oncology, Department of Surgery, University of California, Los Angeles, CA, 90095, USAen
dc.contributor.departmentDepartment of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA, 90095, USAen
dc.contributor.departmentThe Molecular Biology Institute, University of California, Los Angeles, CA, 90095, USAen
dc.contributor.departmentJonsson Comprehensive Cancer Center, University of California, Los Angeles, CA, 90095, USAen
dc.contributor.departmentDepartment of Veterinary Science and Microbiology, The University of Arizona, Tucson, AZ, 85721, USAen
dc.identifier.journalBMC Canceren
dc.description.collectioninformationThis item is part of the UA Faculty Publications collection. For more information this item or other items in the UA Campus Repository, contact the University of Arizona Libraries at repository@u.library.arizona.edu.en
dc.eprint.versionFinal published versionen
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