Abstract
To therapeutically target disseminated tumor cells, while sparing the surrounding tissues, it is necessary to develop agents that interact with structures exposed selectively on the tumor cell surface. Members of the epidermal growth factor receptor family are commonly overexpressed in several tumor types and may serve as targeting structures. In this review we discuss the effects of EGFR and HER2 targeting agents that can deliver radioactive nuclides, i.e. antibodies and affibody molecules, on intracellular signaling. If the targeting agent, in addition to deliver radioactivity to the tumor, can sensitize the tumor for its effects by influencing signal pathways that regulate cell survival and proliferation this will probably be advantageous. We discuss the changes in intracellular signaling that occurs after treatment of cancer cells with the clinically approved monoclonal antibodies cetuximab (anti-EGFR), trastuzumab (anti-HER2) as well as HER2 targeted affibody molecules which are under preclinical development. An important defence mechanism for cells against radiation is to activate DNA repair systems and we also address how DNA repair proteins are regulated in response to radiation or EGFR activation.
Keywords: Affibody, akt, antibody, DNA-repair, EGFR, Erk, HER2, radiation, signal transduction, tumor targeting
Letters in Drug Design & Discovery
Title: Targeting the Epidermal Growth Factor Receptor Family in Radionuclide Therapy of Tumors – Signal Transduction and DNA Repair
Volume: 3 Issue: 6
Author(s): Johan Lennartsson, Jorgen Carlsson and Bo Stenerlow
Affiliation:
Keywords: Affibody, akt, antibody, DNA-repair, EGFR, Erk, HER2, radiation, signal transduction, tumor targeting
Abstract: To therapeutically target disseminated tumor cells, while sparing the surrounding tissues, it is necessary to develop agents that interact with structures exposed selectively on the tumor cell surface. Members of the epidermal growth factor receptor family are commonly overexpressed in several tumor types and may serve as targeting structures. In this review we discuss the effects of EGFR and HER2 targeting agents that can deliver radioactive nuclides, i.e. antibodies and affibody molecules, on intracellular signaling. If the targeting agent, in addition to deliver radioactivity to the tumor, can sensitize the tumor for its effects by influencing signal pathways that regulate cell survival and proliferation this will probably be advantageous. We discuss the changes in intracellular signaling that occurs after treatment of cancer cells with the clinically approved monoclonal antibodies cetuximab (anti-EGFR), trastuzumab (anti-HER2) as well as HER2 targeted affibody molecules which are under preclinical development. An important defence mechanism for cells against radiation is to activate DNA repair systems and we also address how DNA repair proteins are regulated in response to radiation or EGFR activation.
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Lennartsson Johan, Carlsson Jorgen and Stenerlow Bo, Targeting the Epidermal Growth Factor Receptor Family in Radionuclide Therapy of Tumors – Signal Transduction and DNA Repair, Letters in Drug Design & Discovery 2006; 3 (6) . https://dx.doi.org/10.2174/157018006777805503
DOI https://dx.doi.org/10.2174/157018006777805503 |
Print ISSN 1570-1808 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-628X |
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