Role of HER2 in breast cancer (I)

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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

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Role of HER2 in breast cancer (II)

• HER2 gene 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

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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
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Signal Transduction-Directed Cancer
TreatmentsSausville, et a., 2003. Ann. Rev.
Pharmacol. Toxicol. 43199-231.

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1960
The Philadelphia chromosome
a causal relationship between the chromosome
abnormality observed and chronic granulocytic
leukemia.
Peter Nowell
Hungerford
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A specific genetic translocation
1973
Janet Rowley
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Conversion of abl-protooncogene into an oncogene
in myelogenous leukemia
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Abelson kinase (Abl)
1980

• Cytoplasmic protein tyrosine kinase

Bcr-Abl, is an overactive kinase
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Physiologic Regulation by the Normal ABL Protein
and Deregulation by BCR-ABL
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Abl BCR-Abl
nucleus, cytoplasm cytoplasm
nuclear Abl is proapoptotic antiapoptotic
regulated kinase deregulated kinase


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STI1571, Gleevec, Glivac, Imatinib
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Inhibitors of tyrosine kinases
ZD 1839- Iressa----EGFR non-small cell lung
cancer, Tarceva---erlotinib pancreatic cancer