This document discusses the emerging field of personalized medicine and how genomics is enabling more targeted medical treatments. It provides examples of how genetic testing can identify patients who will benefit from certain drugs, like Herceptin for breast cancer patients with high levels of the HER-2 gene. The document also outlines some technical, social, and ethical challenges to widespread adoption of personalized medicine, such as improving genetic testing technologies, educating physicians, and preventing discrimination based on genetic information.

1. GENOMICS AND
PERSONALIZED
MEDICINE
SpecialTopic
By Ms.Watson

2. Introduction
• Physicians have always practiced personalized medicine in order to make effective
treatment decisions for their patients.
• They take into account the patients:
• Lifestyle
• Family history
• Symptoms
• Data derived from many types of medical tests

3. Changes in Personalized Medicine
• Today, personalized medicine is used to describe the application
of information from a patient’s unique genetic profile in order to
select effective treatments that
• minimalize the side-effects
AND/OR
• Detect disease susceptibility prior to the development of the
disease.

4. Sounds good ….What is the problem?
Pharmaceuticals that are available are IMPERFECT
or the process of detection is IMPERFECT

5. Pharmacogenomics
• Pharmacogenomics is the study of how an individual’s entire genetic makeup
determines the body’s response to drugs.
• Pharmacogenomics is interchangeable with pharmocogenetics which refers to the
study of how the sequence varies within specific candidate genes affect an
individual’s drug response.
• In this scientists take into account many aspects of the drug metabolism and how
genetic traits affect these aspects.
• For example the drug can:
• Interact with proteins that will have a problem with the absorption or breakdown of the
drug.

6. Optimizing DrugTherapies
• When it comes to drug therapy, it is clear that “one size does not fit all”.
• On average a drug will be effective in only about 50% of the patients who take it.
• This causes physicians to switch their patients from one drug to another until they
find the perfect match.

7. Optimization with Genomics
• With the help of pharmacogenomics, there is an increase in overall efficiency with
being able to target the specific people who will be benefiting from the drugs.
• One of the most common current applications of this is the diagnosis and
treatment of CANCER!

8. First Success of Personalized Medicine
• HER-2 gene was successfully modified with the use of a medicine called Herceptin
Specifically the human epidermal growth factor receptor 2 gene is located on
chromosome 17 and codes for a transmembrane tyrosine kinase receptor protein
called Her-2.
When these receptors are bound to extracellular growth factors, they cause
transcription of proteins that encourage cell division---AKA CANCER CAUSING
GENES
25% of invasive breast cancers have this over amplified HER-2 gene.

9. Her-2 Demonstration

10. Application of the Herceptin
• Herceptin was developed to assist in the manipulation of the relationship with the
binding to the outside extracellular region of the HER-2.
• As a result it allowed for less of the protein that encouraged cell-division.
• It also only attacked breast cancer cells.
• As a result, they were able to utilize this specific drug for people who specifically
have this overexpression of HER-2.
• SO the doctors can test for the overexpression and particularly use the Herceptin
if the levels are high
• Two types of tests are immunohistochemistry and fluorescence in situ hybridization.

11. Immunohistochemistry(IHC)
• Immunohistochemistry (IHC) refers to the process of selectively imaging
antigens (e.g. proteins) in cells of a tissue section by exploiting the principle of
antibodies binding specifically to antigens in biological tissues.

12. Dozens of Drugs that are Genetically
Chosen
• 10 % of FDA-approved drugs have labels that include pharmacogenomic
information.
• For example, 40 of colon cancer patients respond to the drugs Erbitux and
Zvectibix.
• These two drugs are epidermal growth factor receptors (EGFRs) on the surface of cells
and inhibit the EGFR signal transduction pathway.
• In order to work, cancer cells must express this on their surface.
• This presence can be seen on a microscope so that’s how you can tell before giving the
drug.

14. ReducingAdverse Drug Reactions
• Every year, about 2 million people in the United States have serious side-effects
from pharmaceutical drugs, and approximately 100,000 people die.
• The cost associated with these adverse drug reactions (ADRs) are estimated to be
$136 billion annually.
• Although some of these are from misuse of the drugs, others result from patient’s
inherent physiological reactions to a drug.

15. What is the problem with physiological
differences?
• Sequence variations in a large number of genes can affect drug responsiveness.
• Of particular significance---P450 families of enzymes
• These particular enzyme variants metabolize and eliminate drugs slowly, which
can lead to accumulations of the drug and overdose side-effects.
• Other people have variants that cause drugs to be eliminated quickly leading to
reduced effectiveness.

16. AmpliChip CYP450 Assay
• In 2005, the FDA approved a microarray gene test called the AmpliChip CYP450
Assay that detects 29 genetic variants of the two cytochrome P450 genes---
CYP2D6 and the CYP2C19.
• This test detects single-nucleotide polymorphisms (SNPS) as well as gene
duplications and deletions.
• This is an example of genotyping and a individuals can be created utilizing a
computer.

17. Personalized Medicine and Disease
Diagnosis
As of 2009, there were genetic tests for approximately 2000 different diseases.
These tests are categorized according to their use and can fall into one or more of
these categories:
• Diagnostic tests
• Predictive tests
• Carrier tests
• Preimplantation tests

18. Diagnostic testing
• Testing done to detect the presence or absence of gene variants linked to a
suspected genetic disorder in a symptomatic patient

19. OtherTypes ofTests
• PredictiveTesting-Testing done to detect a gene mutation in patients with a
family history of having a known genetic disorder
• Example: Huntington’s Disease
• CarrierTesting- Help physicians identify patients who carry a gene mutation linked
to a disorder that might be passed on to their offspring
• Example: Cystic Fibrosis
• PreimplantationTesting- performed on early embryos in order to select embryos
for implantation that do not carry a suspected disease.

20. BUTTHERE ARE MANY
CHALLENGING?

21. Technical Challenges
• There are still many technical hurdles to overcome before personalized medicine
will become a standard part of medical care.
• Genome sequencing, microarray analysis, and SNP detection need to be faster,
more accurate, and cheaper.
• Because of these challenges we need to cautious about actually utilizing the information
gathered from these types of tests
• Amount of data is also a big problem since there is so much of it now!
• Need to develop online/ automated health information technologies.
• Currently there are fewer than 10% of hospitals in the US with access to this type of
technology.

22. Social Challenges
• Physicians need the education of genomics.
• Medical schools will need to train physicians to interpret and explain genetic data.
• More genetic counselors and genomic specialist will thus be necessary.

23. Ethical Issues
• Some will argue that these types of tests are a misallocation of resources for
studying.
• Science should solve problems that are facing medicine .
• Needs to be a better way of preventing discrimination of employment or for
insurance companies to potentially utilize this information in a negative way.