Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes.

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Title: Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes.
Authors: Dobroff, Andrey S.1,2, D'Angelo, Sara1,2, Eckhardt, Bedrich L.3, Ferrara, Fortunato1,2, Staquicini, Daniela I.1,2, Cardó-Vila, Marina1,2, Staquicini, Fernanda I.1,2, Nunes, Diana N.4, Kisu Kim5, Driessen, Wouter H. P.6, Hajitou, Amin7, Lomo, Lesley C.1,8, Barry, Marc1,8, Krishnamurthy, Savitri9, Sahin, Aysegul9, Woodward, Wendy A.10, Prossnitz, Eric R.1,2, Anderson, Robin L.11, Dias-Neto, Emmanuel4,12, Brown-Glaberman, Ursa A.1,13
Source: Proceedings of the National Academy of Sciences of the United States of America. 11/8/2016, Vol. 113 Issue 45, p12780-12785. 6p.
Subjects: Inflammatory breast cancer, Breast cancer treatment, Oncology, Glucose-regulated proteins, Biomarkers, Bacteriophages
Abstract: Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibly other cell-surface receptors in human tumors. [ABSTRACT FROM AUTHOR]
Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
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  Data: Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes.
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  Data: <searchLink fieldCode="AR" term="%22Dobroff%2C+Andrey+S%2E%22">Dobroff, Andrey S.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22D'Angelo%2C+Sara%22">D'Angelo, Sara</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Eckhardt%2C+Bedrich+L%2E%22">Eckhardt, Bedrich L.</searchLink><relatesTo>3</relatesTo><br /><searchLink fieldCode="AR" term="%22Ferrara%2C+Fortunato%22">Ferrara, Fortunato</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Staquicini%2C+Daniela+I%2E%22">Staquicini, Daniela I.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Cardó-Vila%2C+Marina%22">Cardó-Vila, Marina</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Staquicini%2C+Fernanda+I%2E%22">Staquicini, Fernanda I.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Nunes%2C+Diana+N%2E%22">Nunes, Diana N.</searchLink><relatesTo>4</relatesTo><br /><searchLink fieldCode="AR" term="%22Kisu+Kim%22">Kisu Kim</searchLink><relatesTo>5</relatesTo><br /><searchLink fieldCode="AR" term="%22Driessen%2C+Wouter+H%2E+P%2E%22">Driessen, Wouter H. P.</searchLink><relatesTo>6</relatesTo><br /><searchLink fieldCode="AR" term="%22Hajitou%2C+Amin%22">Hajitou, Amin</searchLink><relatesTo>7</relatesTo><br /><searchLink fieldCode="AR" term="%22Lomo%2C+Lesley+C%2E%22">Lomo, Lesley C.</searchLink><relatesTo>1,8</relatesTo><br /><searchLink fieldCode="AR" term="%22Barry%2C+Marc%22">Barry, Marc</searchLink><relatesTo>1,8</relatesTo><br /><searchLink fieldCode="AR" term="%22Krishnamurthy%2C+Savitri%22">Krishnamurthy, Savitri</searchLink><relatesTo>9</relatesTo><br /><searchLink fieldCode="AR" term="%22Sahin%2C+Aysegul%22">Sahin, Aysegul</searchLink><relatesTo>9</relatesTo><br /><searchLink fieldCode="AR" term="%22Woodward%2C+Wendy+A%2E%22">Woodward, Wendy A.</searchLink><relatesTo>10</relatesTo><br /><searchLink fieldCode="AR" term="%22Prossnitz%2C+Eric+R%2E%22">Prossnitz, Eric R.</searchLink><relatesTo>1,2</relatesTo><br /><searchLink fieldCode="AR" term="%22Anderson%2C+Robin+L%2E%22">Anderson, Robin L.</searchLink><relatesTo>11</relatesTo><br /><searchLink fieldCode="AR" term="%22Dias-Neto%2C+Emmanuel%22">Dias-Neto, Emmanuel</searchLink><relatesTo>4,12</relatesTo><br /><searchLink fieldCode="AR" term="%22Brown-Glaberman%2C+Ursa+A%2E%22">Brown-Glaberman, Ursa A.</searchLink><relatesTo>1,13</relatesTo>
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  Data: <searchLink fieldCode="DE" term="%22Inflammatory+breast+cancer%22">Inflammatory breast cancer</searchLink><br /><searchLink fieldCode="DE" term="%22Breast+cancer+treatment%22">Breast cancer treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Oncology%22">Oncology</searchLink><br /><searchLink fieldCode="DE" term="%22Glucose-regulated+proteins%22">Glucose-regulated proteins</searchLink><br /><searchLink fieldCode="DE" term="%22Biomarkers%22">Biomarkers</searchLink><br /><searchLink fieldCode="DE" term="%22Bacteriophages%22">Bacteriophages</searchLink>
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  Data: Inflammatory breast carcinoma (IBC) is one of the most lethal forms of human breast cancer, and effective treatment for IBC is an unmet clinical need in contemporary oncology. Tumor-targeted theranostic approaches are emerging in precision medicine, but only a few specific biomarkers are available. Here we report up-regulation of the 78-kDa glucose-regulated protein (GRP78) in two independent discovery and validation sets of specimens derived from IBC patients, suggesting translational promise for clinical applications. We show that a GRP78-binding motif displayed on either bacteriophage or adeno-associated virus/phage (AAVP) particles or loop-grafted onto a human antibody fragment specifically targets orthotopic IBC and other aggressive breast cancer models in vivo. To evaluate the theranostic value, we used GRP78-targeting AAVP particles to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) transgene, obtaining simultaneous in vivo diagnosis through PET imaging and tumor treatment by selective activation of the prodrug ganciclovir at tumor sites. Translation of this AAVP system is expected simultaneously to image, monitor, and treat the IBC phenotype and possibly other aggressive (e.g., invasive and/or metastatic) subtypes of breast cancer, based on the inducible cell-surface expression of the stress-response chaperone GRP78, and possibly other cell-surface receptors in human tumors. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Proceedings of the National Academy of Sciences of the United States of America is the property of National Academy of Sciences and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
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        Text: English
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