title: Towards a transcriptome-based theranostic platform for unfavorable breast cancer phenotypes.
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 humanHerpes simplexvirus 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 possibily other cell-surface receptors in human tumors.
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Andrey S
authors: AS
authors: Dobroff
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Sara
authors: S
authors: D'Angelo
authors: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Bedrich L
authors: BL
authors: Eckhardt
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Fortunato
authors: F
authors: Ferrara
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Daniela I
authors: DI
authors: Staquicini
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Marina
authors: M
authors: Cardó-Vila
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Fernanda I
authors: FI
authors: Staquicini
authors: International Research Center, A. C. Camargo Cancer Center, Sao Paulo 01508-010, Brazil.
authors: Diana N
authors: DN
authors: Nunes
authors: MOGAM Biotechnology Institute, Yongin, Gyeonggi-do 16924, Korea.
authors: Kisu
authors: K
authors: Kim
authors: David H. Koch Center, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Wouter H P
authors: WHP
authors: Driessen
authors: Hammersmith Hospital Campus, Imperial College London, London W12 0NN, United Kingdom.
authors: Amin
authors: A
authors: Hajitou
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Lesley C
authors: LC
authors: Lomo
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Department of Pathology, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Marc
authors: M
authors: Barry
authors: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Savitri
authors: S
authors: Krishnamurthy
authors: Department of Pathology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Aysegul
authors: A
authors: Sahin
authors: Department of Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Wendy A
authors: WA
authors: Woodward
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Eric R
authors: ER
authors: Prossnitz
authors: Department of Oncology, Sir Peter MacCallum Cancer Centre, The University of Melbourne, Parkville, VIC 3010, Australia.
authors: Robin L
authors: http://orcid.org/0000-0002-6841-7422
authors: RL
authors: Anderson
authors: International Research Center, A. C. Camargo Cancer Center, Sao Paulo 01508-010, Brazil.|Institute of Psychiatry, University of São Paulo Medical School, Sao Paulo 01060-970, Brazil.
authors: Emmanuel
authors: E
authors: Dias-Neto
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Ursa A
authors: UA
authors: Brown-Glaberman
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Melanie E
authors: ME
authors: Royce
authors: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Naoto T
authors: NT
authors: Ueno
authors: Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611.
authors: Massimo
authors: M
authors: Cristofanilli
authors: Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030.
authors: Gabriel N
authors: GN
authors: Hortobagyi
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.|Candiolo Cancer Institute-Fondazione del Piemonte per l'Oncologia, Istituto di Ricovero e Cura a Carattere Scientifico, Candiolo, Turin 10060, Italy.|Department of Oncology, University of Turin, Candiolo, Turin 10060, Italy.
authors: Serena
authors: S
authors: Marchiò
authors: Department of Biomedical Engineering, Wayne State University, Detroit, MI 48201.
authors: Juri G
authors: JG
authors: Gelovani
authors: Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215 richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu.
authors: Richard L
authors: RL
authors: Sidman
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu.|Division of Hematology/Oncology, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Wadih
authors: W
authors: Arap
authors: University of New Mexico Comprehensive Cancer Center, Albuquerque, NM 87131; richard_sidman@hms.harvard.edu rpasqual@salud.unm.edu warap@salud.unm.edu.|Division of Molecular Medicine, Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131.
authors: Renata
authors: R
authors: Pasqualini
keywords: AAVP; gene therapy; inflammatory breast cancer; ligand-directed theranostics; molecular imaging