Reversion of the ErbB malignant phenotype and the DNA damage response |
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| Authors: | E. Aaron Runkle Hongtao Zhang Zheng Cai Zhiqiang Zhu Barry L. Karger Shiaw-Lin Wu Donald M. O'Rourke Zhaocai Zhou Qiang Wang Mark I. Greene |
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| Affiliation: | 1. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;2. The Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, MA 02115, USA;3. Department of Neurosurgery, University of Pennsylvania, Philadelphia, PA 19104, USA;4. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China;5. Women''s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA |
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| Abstract: | The ErbB or HER family is a group of membrane bound tyrosine kinase receptors that initiate signal transduction cascades, which are critical to a wide range of biological processes. When over-expressed or mutated, members of this kinase family form homomeric or heteromeric kinase assemblies that are involved in certain human malignancies. Targeted therapy evolved from studies showing that monoclonal antibodies to the ectodomain of ErbB2/neu would reverse the malignant phenotype. Unfortunately, tumors develop resistance to targeted therapies even when coupled with genotoxic insults such as radiation. |
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