Journal article

Inhibition of Established Micrometastases by Targeted Drug Delivery via Cell Surface-Associated GRP78

Yu Rebecca Miao, Bedrich L Eckhardt, Yuan Cao, Renata Pasqualini, Pedram Argani, Wadih Arap, Robert G Ramsay, Robin L Anderson

CLINICAL CANCER RESEARCH | AMER ASSOC CANCER RESEARCH | Published : 2013

Abstract

PURPOSE: The major cause of morbidity in breast cancer is development of metastatic disease, for which few effective therapies exist. Because tumor cell dissemination is often an early event in breast cancer progression and can occur before diagnosis, new therapies need to focus on targeting established metastatic disease in secondary organs. We report an effective therapy based on targeting cell surface-localized glucose-regulated protein 78 (GRP78). GRP78 is expressed normally in the endoplasmic reticulum, but many tumors and disseminated tumor cells are subjected to environmental stresses and exhibit elevated levels of GRP78, some of which are localized at the plasma membrane. EXPERIMENTA..

View full abstract

Grants

Awarded by National Breast Cancer Foundation


Awarded by NATIONAL CANCER INSTITUTE


Funding Acknowledgements

This project was supported by grants from the Association for International Cancer Research (AICR; to R. L. Anderson and R. Pasqualini), the National Health and Medical Research Council (NHMRC) program(to R. G. Ramsay), The Department of Defense Congressionally Directed Medical Research Programs: Breast Cancer Research Program Impact Award (to R. Pasqualini), and the Marcus Foundation (to W. Arap and R. Pasqualini). Fellowship support from the National Breast Cancer Foundation of Australia (to R. L. Anderson), from the NHMRC(to R. G. Ramsay), The Susan G. Komen for the Cure (to B. L. Eckhardt), and The University of Melbourne Postgraduate Scholarships (to Y.R. Miao and Y. Cao) are gratefully acknowledged.R. Pasqualini and W. Arap have a commercial research grant and ownership interest (including patents) and are scientific advisory boardmembers of Arrowhead Corporation. No potential conflicts of interest were disclosed by the other authors.