Development of Precise Pharmocodiagnostic (PharmDx) Tests for Molecular Targeted Therapies(<SPECIAL ISSUE>Tokyo Satellite Symposium "Contribution of Histochemistry in Basic Science and Clinical Medicine")
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概要
- 論文の詳細を見る
Advanced biomolecular technologies have begun to provide beneficial means to detect a variety of cellular molecules for tumor diagnosis, as well as predictive and prognostic factors of cancers. This new understanding of the molecular basis of cancers has led to the development of molecular targeted approaches to cancer prevention and treatment. Molecules involved in the growth factor signaling system have become favored targets for molecular targeted therapies in translational research and clinical development. The current molecular targeting agents are classified into humanized or camera monoclonal antibodies and small-molecule tyrosine kinase inhibitors. Patients with HER2-overexpressing, metastatic breast cancer are beginning to benefit from the first commercially humanized monoclonal antibody (Herceptin), and the first small-molecule tyrosine kinase inhibitor (Gleevec/Glivec) has been introduced in Japan. Gleevec/Glivec has been demonstrated to have a long-term clinical benefit for most refractory patients with Philadelphia chromosome-positive chronic myelogenous leukemia as well as with KIT-expressing, unresectable and/or metastatic gastrointestinal stromal tumor. Accurate and reliable HER2 or KIT testing is performed to determine patient eligibility for Herceptin or Gleevec/Glivec therapy, respectively. HER1 (EGFR) and HER2 are the most widely studied target molecules for therapeutic inhibitions. HER family targeting has been initiated as the basis of extensive and growing drug development programs in various companies. A key technology of targeted therapies is molecular diagnosis with target identification. Along with the progressive development of HER-targeted therapies, the need to standardize immunohistochemical diagnostic tests for each targeted therapy is ever more pressing. Although the standardization of immunohistochemistry using archival formalin-fixed specimens is a tremendous challenge that will require great effort and considerable research, the development of an ideal pharmDx test for target molecular identification will be achieved by the optimal combination of heat-induced antigen retrieval with calcium-chelating solutions, effective signal amplification, and automated staining approaches. The expression levels and phosphorylation/activation of various signaling molecules will be valuable in defining subpopulations of patients who may potentially respond to molecular targeted therapies.
- 日本組織細胞化学会の論文
著者
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Tani Yoichi
Department Of Biomedical Science Dakocytomation Co. Ltd.
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Hashizume Kaoru
Department Of Biomedical Science Dakocytomation Co. Ltd.
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Hatanaka Yutaka
Department Of Biomedical Science Dakocytomation Co. Ltd.
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Hatanaka Yutaka
Department Of Biochemistry Osaka University Medical School
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- Development of Precise Pharmocodiagnostic (PharmDx) Tests for Molecular Targeted Therapies(Tokyo Satellite Symposium "Contribution of Histochemistry in Basic Science and Clinical Medicine")
- Induction of Apoptotic Cell Death in Human Endothelial Cells Treated with Snake Venom: Implication of Intracellular Reactive Oxygen Species and Protective Effects of Glutathione and Superoxide Dismutases.