Pharmacogenomics : When drug

treatment becomes
personalized medicine

Sandeep.P.Kulkarni
 Contents
• Introduction to Pharmacogenomics.

• How exactly this field works????

• Benefits of pharmacogenomics.

• Barriers for using pharmacogenomics.

• Types of personalized medicines being used today.

• Where does the science of pharmacogenomics stand now?

 Introduction to Pharmacogenomics
• The field of pharmacogenomics promises to offer personalized medicine
treatments based on your genetic profile.

• In medicine, one size doesn't fit all . Two people who take the same
cancer medication, for instance, may have very different responses.

• One may have severe, even life-threatening side effects, while the other
experiences few if any side effects and seems to sail through treatment.

• Or, the drug may shrink a tumor in one person but not in another.

• One major reason this difference happens is because people inherit

variations in their genes. And even slight variations can affect how your
body responds to certain medications
 Pharmacogenomics
Is the study of how an individual’s genetic makeup affects
the body’s response to drugs.

 The key to creating personalised drugs with greater efficacy

and safety

 Combines traditional pharmaceutical sciences with

an understanding of common DNA variations in the
human genome

 The most common DNA variations- SNPs

 Genetic polymorphisms

Exist in a human population when allelic

variants occure with a frequency of

1% or greater
 All patients with same diagnosis

Remove:
(1) non-responders
(2) toxic responders
Treat:
Responders and
Patients Which is more
Not Predisposed to urgent?
Toxicity
What should our
priorities be?
• Pharmacogenomics is the science that studies, among other things,
how individuals react to medications.

• Pharmacogenomics is sometimes described as "personalized" or

"individualized" medicine because it offers the potential to
recommend drug treatment based on your individual genetic
background.

• The field of pharmacogenomics is promising. In fact, a handful of

tests are available that can detect some of these genetic variations
and predict how you're likely to respond to certain medications.

• But pharmacogenomics still isn't widely used, so it's wise to educate

yourself about just what pharmacogenomics can — and can't —
offer.
 How exactly this field works????
• How do genes influence response to medications:
Genes are segments of DNA, which are found in all of
your cells.
• DNA is essentially a chemical operating system for your
body, instructing it how to behave and interact on a
cellular level.
• A basic gene can have many different forms. For
instance, consider the gene that determines hair color.
Normal variations of that gene determine specific hair
color, such as brown or blond.
• Similarly, your genes can determine how you react to a
medication. You may have a genetic variation that makes
the drug stay in your body longer than normal, causing
serious side effects. Or you may have a variation that
makes the medication less potent.
• Personalized medicine: Using pharmacogenomics: Say you're
diagnosed with a certain disease, such as breast cancer, for which
you must take medication. You and your doctor choose a medication
based on standard drug therapy and dosing guidelines for that
disease. Your doctor may also take into account such factors as
your weight, age, medical history and even how any blood relatives
have reacted to the same medication.

• Despite all of that, neither you nor your doctor knows how you'll
actually react to the medication. You may experience terrible side
effects — or none at all. The medication may put your cancer into
remission — or it may have no effect. Consequently, you may have
to return to your doctor many times to adjust the dosage or to switch
medications. This is how medication choices generally work today
— it's often a matter of trial and error .

• Pharmacogenomics could potentially speed up that process. Before

you take a single dose of medication, you may be able to have a
blood test to see which genetic variations you have. The test may
show that you have a variation that's likely to adversely affect how
you respond to the medication. So your doctor skips that drug and
prescribes a different one, or your doctor alters the dose to match
your body's genetics.
 Benefits of Pharmacogenomics.
• Making better medication choices. Each year, some 100,000 Americans die from
adverse reactions to medications and more than 2 million are hospitalized.
• Medications generally undergo a rigorous review and testing process before being
approved for sale.
• But there's still often no way to predict how a certain individual will react to a drug.
• So even if a medication appears safe for most people, some people may have a toxic
reaction to it because of variations in their genes.
• Pharmacogenomics may be able to predict the people likely to have a bad reaction to
a drug before they ever take it.
• It may also be able to predict if you'll respond well to a medication — whether your
tumor will shrink or not.

• Safer dosing options. As it stands now, the dosage of a medication either is a

standard one-size-fits-all dose or is based on factors such as your weight and age.
That might not be good enough, though. A standard dose may prove toxic to one
person and not another, because of their genetic variations.
• Using pharmacogenomics, doctors may get around this problem by predicting which
dose of medication is right for you, not just which particular medication is right. So
you and your doctor may spend less time trying out various dosages to find one that
works well, with the fewest side effects and most benefits for your condition.
• Improvements in drug development. Pharmaceutical
companies often must spend years conducting research
and clinical trials for a new drug before it goes to market.
• They have to test a drug in many people to ensure that
it's safe and effective.
• Pharmacogenomics may help these companies better
focus their drug testing.
• If companies know ahead of time that someone has a
genetic variation that will cause a bad reaction to the
drug or that will make the drug ineffective, those people
can be excluded from the clinical trial.
• This may speed up the clinical trial process and better
target people who can be helped by a certain
medication.
 Barriers for using
pharmacogenomics.
• The field of pharmacogenomics is still in its early
stages.
• It's possible that millions of genetic variations
may exist, and identifying them all could take
many years — if it's even possible.
• In addition, how you respond to a medication
may not be determined by just one gene but
rather by many genes interacting with each
other.
• Combing through this complicated genetic map
is expensive and time-consuming.
 Types of personalized medicines
being used today.
• Cytochrome P450 genotyping test. A group of enzymes known as
cytochrome P450 (CYP450) enzymes are responsible for
metabolizing more than 30 types of medications and thus determine
how quickly and effectively these medications are eliminated from
your body.

• Because of your genetic makeup, your body may not break down
the medications fast enough, instead allowing them to accumulate to
levels that can result in severe side effects.

• Or, you may have a genetic variation that makes your body break
down the medications too quickly, before they have a chance to
work.

• The CYP450 test can be used to determine dosing and effect of

certain antidepressant medications, anticoagulants such as warfarin,
proton pump inhibitors and a number of other medications.
• Thiopurine methyltransferase test. An enzyme
called thiopurine methyltransferase (TPMT)
breaks down a type of chemotherapy drug called
thiopurine that's used to treat some leukemias
and autoimmune disorders.
• Some people have genetic variations that
prevent them from producing this enzyme.
• As a result, thiopurine levels can build up in the
body, leading to severe toxic reactions.
• A blood test can check for this genetic variation
before treatment begins, giving doctors better
dosing guidelines.
• UGT1A1 TA repeat genotype test. This test, commonly
known as the UGT1A1 test, detects a variation in a gene
that affects the UGT1A1 enzyme.
• This enzyme determines how the body breaks down
irinotecan (Camptosar), a chemotherapy drug used to
treat colorectal cancer.
• Some people have a deficiency in this enzyme, allowing
the medication to build up to toxic levels and possibly
causing suppression of the bone marrow, infection and
even death.
• Doctors can test for this genetic variation before
treatment starts and then customize the dosage to
prevent a toxic buildup of the drug.
• On the flip side, if someone has normal levels of the
UGT1A1 enzyme, the test may help doctors ensure that
the dosage of irinotecan isn't lower than necessary.
• Dihydropyrimidine dehydrogenase test. The
medication 5-fluorouracil (5-FU) including its
related compounds is one of the most commonly
used chemotherapy medications.
• Some people have a genetic variation that
results in a decrease in the dihydropyrimidine
dehydrogenase enzyme, which is responsible
for breaking down 5-FU.
• As a result of this deficiency, some people may
develop severe or even fatal reactions to 5-FU.
• Knowing ahead of time who has this deficiency
can help doctors tailor the medication dosage to
prevent these kinds of dangerous adverse
reactions.
 Where does the science of
pharmacogenomics stand now?
• In the future, pharmacogenomics could have an
expanding role in the practice of medicine.
• But despite the promise of personalized
medicine, pharmacogenomic testing is not
widely available today.
• You should be skeptical of news reports and
other sources of information proclaiming that
pharmacogenomics or other types of
personalized medicine will offer revolutionary
results today.
• It is hoped that this will be true sometime in the
future.
THANK YOU