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Role of HER2 in breast cancer (I)

Role of HER2 in breast cancer (I). HER2 is an oncogene involved in abnormal cell growth HER2 gene amplification or protein overexpression produces activated HER2 receptors, which stimulates cell growth. Role of HER2 in breast cancer (II).

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Role of HER2 in breast cancer (I)

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  1. Role of HER2 in breast cancer (I) • HER2 is an oncogene involved in abnormal cell growth • HER2 gene amplification or protein overexpression produces activated HER2 receptors, which stimulates cell growth

  2. Role of HER2 in breast cancer (II) • HER2gene amplification or receptor overexpression occurs in approximately 30% of metastatic breast cancers • HER2-positive tumors are associated with poor prognosis and shortened disease-free/overall survival

  3. INCIDENCE OF RAS GENE MUTATIONS IN HUMAN CANCER TUMOR TYPE INCIDENCE (%) PANCREATIC CARCINOMA 90 COLON CARCINOMA 50 THYROID CARCINOMA 50 LUNG ADENOMA 30 MELANOMA 20 LYMPHOID 10 BLADDER 06

  4. GEF GTP GDP mutant Pi Ras Ras GDP GTP GAP

  5. Signal Transduction-Directed Cancer TreatmentsSausville, et a., 2003. Ann. Rev. Pharmacol. Toxicol. 43:199-231.

  6. 1960 The Philadelphia chromosome …a causal relationship between the chromosome abnormality observed and chronic granulocytic leukemia.” Peter Nowell Hungerford

  7. A specific genetic “translocation” 1973 Janet Rowley

  8. Conversion of abl-protooncogene into an oncogene in myelogenous leukemia

  9. Abelson kinase (Abl) 1980 • Cytoplasmic protein tyrosine kinase Bcr-Abl, is an overactive kinase

  10. Physiologic Regulation by the Normal ABL Protein and Deregulation by BCR-ABL

  11. CONTROL OF GROWTH GF GF RECEPTOR SIGNALING MOLECULES NUCLEAR PROTEINS autocrine Constitutively active Proto-Oncogene Oncogene Normal growth Cancer

  12. STI1571, Gleevec, Glivac, Imatinib

  13. Imatinib-----STI-571---Gleevec Bcr-Abl kit CML PDGFR RTK Sarcoma GIST (CD117 positive) Inhibitors of tyrosine kinases ZD 1839-Iressa----EGFR non-small cell lung cancer, Tarceva---erlotinib pancreatic cancer

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