Pharmacogenetics The study of how an individual s genetic

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Pharmacogenetics
The study of how an individuals genetic
inheritance affects the bodys response to drugs.
The study of genetic variation underlying
differential response to drugs.
Branch of pharmaceutics which aims to tailor
medicines to an individuals genetic makeup.
Is a form of individualized medicine.
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The Herceptin Story
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• HER2 is a proto-oncogene found on chromosome 17.

HER2
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• HER2 stands for Human Epidermal growth factor
  Receptor 2. Each normal breast cell contains
  copies of the HER2 gene, which helps normal cells
  grow. The HER2 gene is found in the DNA of a
  cell, and this gene contains the information for
  making the HER2 protein.

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• The HER2 protein, also called the HER2
  receptor, is found on the surface of some normal
  cells in the body. In normal cells, HER2 proteins
  help send growth signals from outside the cell to
  the inside of the cell. These signals tell the
  cell to grow and divide.

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• In HER2 breast cancer, the cancer cells have
  an abnormally high number of HER2 genes per cell.
  When this happens, too much HER2 protein appears
  on the surface of these cancer cells. This is
  called HER2 protein overexpression.

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• Too much HER2 protein is thought to cause
  cancer cells to grow and divide more quickly.
  This is why HER2 breast cancer is considered
  aggressive.

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Testing a tumor for HER2 using FISH or
Immunohistochemistry (IHC)
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HER2 FISH
In this procedure, the chromosome 17 centromere
is marked with a green florescent signal and
HER-2 gene with an orange florescent signal. 60
non-overlapping tumor cell nuclei are counted and
the number of green and orange signals are
assessed in each cell. Then, the overall
gene-to-chromosome (17) ratio is calculated. A
tumor is designated as positive for gene
amplification if gene-to-chromosome (17) ratio is
gt2.0
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Research
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Trastuzumab (Herceptin)

• The drug Herceptin was discovered by Dennis
  Slamon at UCLA in 1998 and manufactured by
  Genentech scientists.
• It blocks the action of the receptor

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• Trastuzumab was originally developed in mice,
  as a mouse antibody. Because humans have immune
  reactions to mouse proteins, it was later
  developed into a human (humanized) antibody.
• Because the antibodies were produced from one
  cell that was grown into a clone of identical
  cells, it is called a monoclonal antibody.

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Animation
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COST

• 70,000 for a full course of treatment
• Genentech earned 327 million in 2007 4thQ

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Another HER2 drug
Animation
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Support Groups
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An example of a KaplanMeier plot for two
conditions associated with patient survival
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Kaplan-Meier Curve, Herceptin