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

2013 MFMER | 3309825-1

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.

2013 MFMER | 3309825-2

#1 Get Oriented First

2013 MFMER | 3309825-3

Precision
Individualized
Personalized
Medicine
Medicine
Medicine
2013 MFMER | 3309825-4

2013 MFMER | 3309825-5

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.

2013 MFMER | 3309825-6

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.

2013 MFMER | 3309825-7

2013 MFMER | 3309825-8

OK, so whats really behind all this?

2013 MFMER | 3309825-9

Why do some people develop a particular

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

2013 MFMER | 3309825-10

2013 MFMER | 3309825-11

2013 MFMER | 3309825-12

This will revolutionize

the diagnosis,
prevention and
treatment of most ,
if not all, human
diseases.
-Bill Clinton, June 2000
2013 MFMER | 3309825-13

2013 MFMER | 3309825-14

2013 MFMER | 3309825-15

15 Years
$3 Billion
2013 MFMER | 3309825-16

2013 MFMER | 3309825-17

Cost of Whole Genome Sequencing

> $1,000 to sequence

one human genome

?
2013 MFMER | 3309825-18

2013 MFMER | 3309825-19

2013 MFMER | 3309825-20

2013 MFMER | 3309825-21

2013 MFMER | 3309825-22

The waiting is the

hardest part.
-Tom Petty, 1981

2013 MFMER | 3309825-23

2013 MFMER | 3309825-24

#2 The Practice of Medicine is

Transforming

2013 MFMER | 3309825-25

The needs of the

patient come first.

2013 MFMER | 3309825-26

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

2013 MFMER | 3309825-27

2013 MFMER | 3309825-28

Advanced Cancers

We are using the latest genetic sequencing

technologies to move away from a one size fits all
approach to cancer treatment
2013 MFMER | 3309825-29

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
2013 MFMER | 3309825-30

2013 MFMER | 3309825-31

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
2013 MFMER | 3309825-32

Responded to a drug we
would have NEVER thought
of using for this patient.

2013 MFMER | 3309825-33

2013 MFMER | 3309825-34

2013 MFMER | 3309825-35

Challenges
1. While the cost and time to sequence have

plummeted, the analysis still takes time and $$.

2. Sometimes find hits but dont 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

Relevancedoing too early? Cancers evolve!
2013 MFMER | 3309825-36

We are using the power of genomic

sequencing to individualize cancer
treatment.

2013 MFMER | 3309825-37

Diagnostic Odyssey

We are using the latest genetic sequencing

technologies to find answers for people with difficult to
diagnose diseases.
2013 MFMER | 3309825-38

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
2013 MFMER | 3309825-39

2013 MFMER | 3309825-40

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
2013 MFMER | 3309825-41

2013 MFMER | 3309825-42

The patient has started a

therapy (acetazolamide) to
help control symptoms and
improve his quality of life.

2013 MFMER | 3309825-43

2013 MFMER | 3309825-44

Challenges
1. We dont 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

significancemore workmore $$$

3. Doesnt always lead to a treatmentno action

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

how to identify good candidates

2013 MFMER | 3309825-45

We are using the power of genomic

sequencing to find answers for patients
with difficult to diagnose diseases.

2013 MFMER | 3309825-46

2013 MFMER | 3309825-47

#3 Enhancing The Impact

2013 MFMER | 3309825-48

Pharmacogenomics

We are using genetic sequencing technologies to help

get the right drug to the right patient at the right time.
2013 MFMER | 3309825-49

Trial and Error Approach

2013 MFMER | 3309825-50

Patient Safety

Roughly 5% of all hospital admissions are due

to adverse drug reactions (ADRs).
ADRs range from unpleasantto fatal.
2013 MFMER | 3309825-51

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

2013 MFMER | 3309825-52

2013 MFMER | 3309825-53

2013 MFMER | 3309825-54

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.

2013 MFMER | 3309825-55

2013 MFMER | 3309825-56

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.
2013 MFMER | 3309825-57

We are integrating genomic information

in to medical care to avoid giving patients
ineffective and harmful drugs.

2013 MFMER | 3309825-58

Wish there was more time

2013 MFMER | 3309825-59

2013 MFMER | 3309825-60

2013 MFMER | 3309825-61

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

2013 MFMER | 3309825-62

Technology ready?
Ethical and Legal Issues?

Direct to Consumer Testing?

Cost? Insurance?
2013 MFMER | 3309825-63

2013 MFMER | 3309825-64

2013 MFMER | 3309825-65

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.
2013 MFMER | 3309825-66

2013 MFMER | 3309825-67

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 wont work for me?
If I undergo treatment, what is my
risk of side effects?
Now more than ever, the answers
2013 MFMER | 3309825-68

For most human diseases,

our genetics sets a range of
possibilities for usbut it still
matters what we do on a day to
day basis.

2013 MFMER | 3309825-69

Risk is
Subjective
2013 MFMER | 3309825-70

People want
differing levels
of information
about their risk
2013 MFMER | 3309825-71

The same
information
about risk can
be interpreted
very differently
2013 MFMER | 3309825-72

We are moving forward in Predictive

Genomics.

2013 MFMER | 3309825-73

Spidermans Uncle
2013 MFMER | 3309825-74

2013 MFMER | 3309825-75

#4 Dont Forget the Fuel for this

Fire

2013 MFMER | 3309825-76

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.
2013 MFMER | 3309825-77

Investment in Specimen Storage

78

Rochester

Arizona

Florida

2013 MFMER | 3309825-78

2013 MFMER | 3309825-79

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

2013 MFMER | 3309825-80

The Mayo Clinic Biobank

Midwest

Florida

Arizona

2013 MFMER | 3309825-81

21st century resource

2013 MFMER | 3309825-82

2013 MFMER | 3309825-83

2013 MFMER | 3309825-84

#5 Eyes on the Future

2013 MFMER | 3309825-85

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.

2013 MFMER | 3309825-86

Its not just about DNA

2013 MFMER | 3309825-87

Its Not Just About Studying People with

Disease

2013 MFMER | 3309825-88

Its Not Just About Diagnosing and Treating

Disease

2013 MFMER | 3309825-89

2013 MFMER | 3309825-90

2013 MFMER | 3309825-91

2013 MFMER | 3309825-92

2013 MFMER | 3309825-93

Integration of
technology takes
time

but technology waits

for no one.

2013 MFMER | 3309825-94

2013 MFMER | 3309825-95

Disruptive Technology Can Cut Both Ways

23%
2013 MFMER | 3309825-96

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

2013 MFMER | 3309825-97

X-rays will prove

to be a hoax.
Lord Kelvin
President of the Royal
Society, 1883.

2013 MFMER | 3309825-98

2013 MFMER | 3309825-99

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 careits 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 alonea true

team effort.

2013 MFMER | 3309825-100

X
2013 MFMER | 3309825-101

2013 MFMER | 3309825-102

2013 MFMER | 3309825-103

I look through a half-opened door into

the future, full of interest, intriguing
beyond my power to describe
-Dr. William Mayo

2013 MFMER | 3309825-104

Thanks.

2013 MFMER | 3309825-105

2013 MFMER | 3309825-106

One more thing

2013 MFMER | 3309825-107

2013 MFMER | 3309825-109

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

2013 MFMER | 3309825-111

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.
2013 MFMER | 3309825-112