Precision Medicine

The Big Picture
Alexander Parker, PhD
Professor of Urology and Epidemiology
Cecilia and Dan Carmichael Family Associate Director for the Center for
Individualized Medicine

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1. I am, without a doubt, the warm-up act. The

deep dives from the heavy hitters come later.
2. This talk is about the entire field of precision

medicine, so when I use the word “we” I do not
mean Mayo Clinic.
3. I will use examples from our practice to illustrate

some key points.
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#1 Get Oriented First…

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Precision
Individualized
Personalized
Medicine
Medicine
Medicine
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Discover and translate new opportunities for
individualizing the prevention, diagnosis and
treatment of disease through the use of the most
advanced molecular and clinical technologies
available.

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Discover and translate new opportunities for
individualizing the prevention, diagnosis and
treatment of disease through the use of the most
advanced molecular and clinical technologies
available.

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OK, so what’s really behind all this?

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Why do some people develop a particular
disease and others don’t?
Why do some people respond to a particular
treatment and others don’t?
Why do some people insist on cheering for
Duke and not North Carolina?

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“This will revolutionize
the diagnosis,
prevention and
treatment of most ,
if not all, human
diseases.”
-Bill Clinton, June 2000
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15 Years
$3 Billion
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Cost of Whole Genome Sequencing

> $1,000 to sequence
one human genome

?
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“The waiting is the
hardest part.”
-Tom Petty, 1981

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#2 The Practice of Medicine is
Transforming…

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The needs of the
patient come first.

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Individualized Medicine Clinic

Referral to IM Clinic
and Consultation

Sample Collection
(Blood and/or Tissue)

Individualized
Medicine Consult

1. Referral-based

Expert Review and
Consultation

Next Generation
Sequencing

Data Storage/Analysis

Interpretive Report
Generated

2. Starts and Ends with Patient
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Advanced Cancers

We are using the latest genetic sequencing
technologies to move away from a “one size fits all”
approach to cancer treatment
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One Size Does Not Fit All…
• 44-year-old female with cancer in her gall bladder
• Cancer has spread to her lungs
• Her cancer did not respond to the

“standard therapy”
• She enrolled in a clinical trial of a possible new

drug for cancers of the gall bladder
• No response…
• Out of options
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Individualized Medicine Clinic
Provides a New Hope
• Her oncologist consulted with the Mayo Individualized





Medicine Clinic
Team discussed her case and determined she is good
candidate for genomic sequencing
Genetic Counselor met with patient and her oncologist to
explain pros and cons
Resected the cancer and isolated DNA
Sequenced the DNA from the tumor and our team
analyzed it for “clues”
Identified a mutation in a gene called FGFR2
Started targeted therapy against FGFR2 (used in
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Responded to a drug we
would have NEVER thought
of using for this patient.

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Challenges
1. While the cost and time to sequence have

plummeted, the analysis still takes time and $$.
2. Sometimes find “hits” but don’t know what they

mean.
3. Sometimes find “hits” but there is no drug to

give.
4. Waiting too late, so should just sequence

earlier…

Issues of standard of care
Relevance…doing too early? Cancers evolve!
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We are using the power of genomic
sequencing to individualize cancer
treatment.

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Diagnostic Odyssey

We are using the latest genetic sequencing
technologies to find answers for people with difficult to
diagnose diseases.
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Everyone Deserves Answers…
• 23 year old male with tremor, spasticity and mild

intellectual disability
• Episodes of uncontrollable movements


Safety risk due to falls
Impact ability to perform activities of daily living
Movements keep him awake at night

• Clinical and genetic evaluations were all

inconclusive
• Seen by > 5 Neurologists at multiple institutions
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Individualized Medicine Clinic
Provides a New Hope
• Mayo Neurologist consulted with the Individualized




Medicine Clinic.
Team discussed the case and determined this patient is
good candidate for genomic sequencing.
Genetic Counselor met with patient and family to explain
pros and cons.
Obtained blood samples from the patient, both biological
parents and the biological (unaffected) sister.
Sequenced the DNA from all four individuals
analyzed it for “clues”.
Identified a mutation in a gene called KCNA1 which lead
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The patient has started a
therapy (acetazolamide) to
help control symptoms and
improve his quality of life.

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Challenges
1. We don’t always find the answer, sometimes

we come up empty

Published rates are ~25% of the time we get a
answer in these cases

2. Can unearth a lot of “variants of unknown

significance”…more work…more $$$
3. Doesn’t always lead to a treatment…no action

we can take.
4. Educating physicians about the potential and

how to identify good candidates
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We are using the power of genomic
sequencing to find answers for patients
with difficult to diagnose diseases.

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#3 Enhancing The Impact…

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Pharmacogenomics

We are using genetic sequencing technologies to help
get the “right drug to the right patient at the right time”.
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Trial and Error Approach

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Patient Safety

• Roughly 5% of all hospital admissions are due
to adverse drug reactions (ADRs).
• ADRs range from unpleasant…to fatal.
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“The power in tailored therapeutics is for
us to say more clearly to payers,
providers and patients… ‘this treatment is
not for everyone, but it is for you’.”
John C. Lechleiter
President and CEO, Eli Lilly and Company

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Challenge
1. Several important pharmacogenetic

tests have been available for many
years, and yet their adoption in the clinic
remains uncommon.
• Fragmented health care system
• Low use of EMRs and difficulty integrating

with existing EMRs
• System that does not reward prevention

2. Lack of specific guidelines on how to

adjust medications on the basis of the
genetic test results.

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The Clinical Pharmacogenetics Implementation Consortium

Provide peer-reviewed, updated, evidence-based,
freely accessible guidelines for gene/drug pairs
that will facilitate the translation of
pharmacogenomic knowledge
from bench to bedside.
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We are integrating genomic information
in to medical care to avoid giving patients
ineffective and harmful drugs.

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Wish there was more time…

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The Emerging Issue…
• Healthy individuals expressing interest in the use of

genomic medicine ( “Worried Well”, “Healthy but
Curious”, etc.).
• “Predictive Genomics”
• Up until now we were discussing this in context of a

specific disease (known or unknown)
• Now moving in to scenario that loses that context

Deeper bioethical debate
Insurance coverage for service unlikely

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Technology ready?
Ethical and Legal Issues?

Direct to Consumer Testing?
Cost? Insurance?
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Predictive Genomics

We are offering a menu of genomic services to
address the needs of “healthy” patients interested in
accessing more information they can use to
enhance their health and wellness.
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Disease Raises Many Questions…
What is my risk of developing Disease
X?
If I have Disease X, what is the risk I
will die from it?
If I chose a treatment for Disease X,
what is the risk it won’t work for me?
If I undergo treatment, what is my
risk of side effects?
Now more than ever, the answers
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For most human diseases,
our genetics sets a range of
possibilities for us…but it still
matters what we do on a day to
day basis.

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Risk is
Subjective
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People want
differing levels
of information
about their risk
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The same
information
about risk can
be interpreted
very differently
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We are moving forward in Predictive
Genomics.

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Spiderman’s Uncle
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#4 Don’t Forget the Fuel for this
Fire…

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Research has and will continue to drive this
movement…
Without the
ability to collect,
store and
analyze
biological
specimens, the
Individualized
Medicine
movement will
stagnate.
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Investment in Specimen Storage
78

Rochester

Arizona

Florida

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“We must begin now to prepare for the future;
we cannot wait until the details are known or
fully understood, nor can we expect that others
will address our concerns or solve our
problems….”
David B. Schowalter, M.D. (1960-2007)
Department of Medical Genetics
Founder, Biospecimen Trust and
Oversight Group

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The Mayo Clinic Biobank

Midwest

Florida

Arizona

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21st century resource…

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#5 Eyes on the Future…

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Discover and translate new opportunities for
individualizing the prevention, diagnosis and
treatment of disease through the use of the most
advanced molecular and clinical technologies
available.

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It’s not just about DNA…

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It’s Not Just About Studying People with
Disease…

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It’s Not Just About Diagnosing and Treating
Disease…

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Integration of
technology takes
time…

…but technology waits
for no one.

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Disruptive Technology Can Cut Both Ways…

23%
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“I think there is a
world market for
maybe five
computers.”
Thomas Watson,
Chairman of IBM, 1943

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“X-rays will prove
to be a hoax.”
Lord Kelvin
President of the Royal
Society, 1883.

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A Couple Things to Take Forward…
1.

Advances in genomic sequencing are at the
heart of the precision medicine movement.

2.

We are using new genomic sequencing
technology to guide patient care…it’s a reality.

3.

This is a transformative time… but it is early.
The promise is still outweighing the reality.

4.

There are a number of challenges and
opportunities as we move forward.

5.

No one will accomplish this alone…a true
team effort.

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X
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“I look through a half-opened door into
the future, full of interest, intriguing
beyond my power to describe…”
-Dr. William Mayo

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Thanks.

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One more thing…

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Challenge
• Several important pharmacogenetic

tests have been available for many
years, and yet their adoption in the clinic
remains uncommon.
• Fragmented health care system
• Low use of EMRs
• System that does not reward prevention

• Lack of specific guidelines on how to

adjust medications on the basis of the
genetic test results.
©2013 MFMER | 3309825-110

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The Clinical Pharmacogenetics Implementation Consortium

Provide peer-reviewed, updated, evidence-based,
freely accessible guidelines for gene/drug pairs
that will facilitate the translation of
pharmacogenomic knowledge
from bench to bedside.
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