期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 38, 页码 15389-15394出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1313857110
关键词
combination therapy; signal transduction
资金
- US National Cancer Institute [CA072981]
- European Research Council
- Seventh Framework Program of the European Commission
- German-Israeli Project Cooperation (DIP)
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- M.D. Moross Cancer Institute
- Julius Baer Trust
- Dukler Mudy Grant
- Sergio Lombroso Foundation
Due to intrinsic aggressiveness and lack of effective therapies, prognosis of pancreatic cancer remains dismal. Because the only molecular targeted drug approved for pancreatic ductal adenocarcinoma is a kinase inhibitor specific to the epidermal growth factor receptor (EGFR), and this receptor collaborates with another kinase, called HER2 (human EGF-receptor 2), we assumed that agents targeting EGFR and/or HER2 would effectively retard pancreatic ductal adenocarcinoma. Accordingly, two immunological strategies were tested in animal models: (i) two antibodies able to engage distinct epitopes of either EGFR or HER2 were separately combined, and (ii) pairs of one antibody to EGFR and another to HER2. Unlike the respective single monoclonal antibodies, which induced weak effects, both types of antibody combinations synergized in animals in terms of tumor inhibition. Immunological cooperation may not depend on receptor density, antigenic sites, or the presence of a mutant RAS protein. Nevertheless, both types of antibody combinations enhanced receptor degradation. Future efforts will examine the feasibility of each strategy and the potential of combining them to achieve sustained tumor inhibition.
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