PRECISION MEDICINE: A REVOLUTION IN

HEALTH
BY
DR NOOR KAMIL

WHAT IS PRECISION MEDICINE?

Precision medicine is a medical model that proposes the customization of healthcare - with

medical decisions, practices, and/or products being tailored to the individual patient. In this
model, diagnostic testing is often employed for selecting appropriate and optimal therapies
based on the context of a patient's genetic content or other molecular or cellular analysis.
Tools employed in PM can include molecular diagnostics, imaging, and analytics/software.
Precision medicine is a model of medicine where medical history is cross-referenced with

biological patterns to provide more preventative and effective diagnosis and treatment.
Tracing biological patterns is dependent on DNA, and it can reveal drug responsiveness,

health risks and inherited conditions.

THE RIGHT TREATMENTS AT THE RIGHT TIME, EVERY TIME,

TO THE RIGHT PERSON.
Precision medicine implies that, diseases are defined by underlying molecular mechanisms

rather than traditional signs and symptoms.

Far too many diseases we do not have a proven means of prevention or effective

treatments. We must gain better insights into the biology of these diseases.
Precision medicine is an emerging approach for disease treatment and prevention that

takes into account individual variability in genes, environment, and lifestyle for each
person. While significant advances in precision medicine have been made for selected
cancers, the practice is not currently in use for most diseases.
Many efforts are underway to help make precision medicine the norm rather than the

exception.
In US to accelerate the pace, Obama has unveiled the Precision Medicine Initiative a bold

new enterprise to revolutionize medicine and generate the scientific evidence needed to
move the concept of precision medicine into every day clinical practice.

MEDICINE: PAST AND FUTURE

Past

Future

Mass Medicine

Precision Medicine

Designed for average patient

Highly effective drugs for defined

patients

One-size fits all prescription

Treatment can be very successful to

Offering highly effective therapeutic

some but not for others

options for precisely defined patient

populations based on molecular targeting

PRECISION MEDICINE: DEFINED AND COMPARED

Current medical practice:
Use vital signs today relative to last visit; assess symptoms; physician uses expert background,

experience and judgment to diagnose, prescribe

Personalized medicine:
Collect and analyze extensive information and data about patient, EHR (electronic health record)

to genome and beyond; physician uses this information and data to make more informed diagnosis
and treatment plan

Precision medicine:
Use massive data network that aggregates and analyzes information from huge patient cohorts,

healthy populations, experimental organisms and reaches toward disease mechanisms, and
precision diagnosis and treatment for each individual

Focused on
pattern
recognition
Results can be
predicted
probabilisticall
y
Caregivers can
follow the
odds but not
yet guarantee
specific
outcomes for
individuals

Precision
Medicine

Empirical
Medicine

Intuitive
Medicine

Conditions are
diagnosed by
their
symptoms
Treatment
efficacy is
uncertain
Should be
charged on
fee-for-service
basis

Disease cause
are
understood
Exact
diagnosis is
routine
Conditions are
treatable with
predictable
effective rulesbased
therapies
Should be
charged on
the fee-foroutcome basis

EARTH SHATTERING DNA EDITING TECH

DNA testing has become increasingly useful in the detection and treatment of various

conditions, including cancer, intellectual developmental delays, birth defects, and diseases
of unknown origin.
CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats): use of

edit DNA as easily as cutting and pasting words on a laptop. Soon it will allow to perform
miraculous fixes to eliminate or alter mutations that cause everything from some cancers
to Parkinsons disease.

PRECISION
MEDICINE
Precision Medicine is an approach to discovering and developing medicines and vaccines that

deliver superior outcomes for patients, by integrating clinical and molecular information to
understand the biological basis of disease.
This effort leads to better selection of disease targets and identification of patient populations

that demonstrate improved clinical outcomes.

Precision medicineis the application ofpanomic analysis(genomics,proteomics,

metabolomics,transcriptomics) andsystems biologyto analyze the cause of an individual

patient's disease at the molecular level and then to utilizetargeted treatments(possibly in
combination) to address that individual patient's disease process. The patient's response is then
tracked as closely as possible, often using surrogate measures such as tumor load (true
outcomes, such as 5 year survival rate), and the treatment finely adapted to the patient's
response.
The branch of precision medicine that addresses cancer is referred to as "precision oncology".

 Inter-personal difference ofmolecular pathologyis diverse, so as inter-personal difference in the

exposome, which influence disease processes through theinteractomewithin thetissue

microenvironment, differentially from person to person.
As the theoretical basis of precision medicine, the unique disease principle emerged to embrace

the ubiquitousphenomenonofheterogeneityofdiseaseetiologyandpathogenesis. The unique

disease principle was first described in neoplastic diseases as the unique tumor principle.
As the exposome is a commonconceptof epidemiology, precision medicine is intertwined with

molecular pathological epidemiology(MPE).

MPE research is capable of identifying potentialbiomarkersfor precision medicine.

An innovative approach to disease prevention and treatment that takes into account individual
differences in peoples genes, environments, and lifestyles

 "Precision medicine," also known as "personalized medicine," is the term

used for this transformative new model of health carethat involves the
selection of diagnostic tests that have the potential to identify changes in each
individual patient's diseased cells.
Personalized medicine combines established clinical parameters and emerging

molecular information to create preventive, diagnostic and therapeutic solutions

tailored to individual patient requirements.
Precision medicine offers meaningful changes in healthcare refining diagnosis,

treatment and patient prognosis, and bringing large efficiency savings.

Recent biotechnological advances have led to an explosion of disease-relevant

molecular information that has brought the promise of personalized medicine within
reach.
Already, the cost of obtaining a single human-genome sequence has fallen from US$

95 million in 2001 to only about US$ 21,000 in January 2011, and is now shrink
further to US$ 1,000 recently.

CANCER PATIENTS FACE ALL SIMILAR CHALLENGESBUT

EACH PATIENT'S CANCER IS UNIQUE
Cancers are categorized according to anatomical site of origin (i.e., breast cancer,

prostate cancer, lung cancer, etc.), yet oncologists have long recognized that
people with the "same" cancer do not always respond the same way to the same
medicinein other words, every patient's cancer is unique, driven by distinct
biological factors.
In recent years, dramatic advances in molecular biology, genomics, and related

technologies have resulted in greater understanding of the mechanisms of cancer

at the molecular level.
It is now possible not only to identify the genetic and molecular variations in each

patient's cancer cells, but to apply the results from the tumor profile, in some
circumstances, to begin treatment strategies that target the molecular
underpinnings of the specific disease in each patient.

PRECISION MEDICINE CONCEPT: IDENTIFY THE TARGETS TO BE TREATED IN EACH PATIENT

What is the optimal

Biotechnology ?

Clinical evidence
Therapy matched
to genomic
alteration

Molecular analysis

What is the optimal

Algorithm ?
Target identification

Andre, ESMO, 2012

Deactivated T-cell, immune checkpoint inhibitor

When the immune system is
stimulated, T-cells make interferon,
which promotes PD-L1 expression
by the tumor cells. When PD-L1
binds to PD-1 on the T-cell, the Tcell becomes deactivated, allowing
the cancer cell to evade immune
attack.
Activated T-cell, immune checkpoint inhibitor

PD-1 and PD-L1 inhibitors can prevent

the tumor cell from binding to PD-1,
enabling the T-cell to remain active
and co-ordinate an attack.

Adoptive immunotherapy

Cell signilling inhibitors

PERSONALIZED VS PRECISION
Non-genetic physician comments: We practice personalized medicine every day. Its called

basic patient care! For example, one RA patient may prefer to have a drug infusion once per
month and another patient may prefer to take a pill each day.
TheNature Medicinearticle emphasizes the idea that molecular information improves the

precision with which patients are categorized and treated.

Personalized medicine might say patient X with disease Y should get drug Z,
Precision medicine says patient X has a subset of disease Y actually, disease Y3, not disease

Y1, Y2 or Y4 and patients with disease Y tend to respond more favorably to drug Z.
Charles Sawyers, an oncologist at the Memorial Sloan-Kettering Cancer Center in New York: we

are trying to convey a more precise classification of disease into subgroups that in the past
have been lumped together because there wasnt a clear way to discriminate between them.
Around the time of the completion of the human genome project in 2000, there was hope that

genetic markers would clearly segment patients into responders and non-responders. However,
this has not yet happened, in part because complex traits including PGx
(pharmacogenetics) predictors of response to drugs are highly polygenic.

 A more realistic perspective on the role of genetics in patient care is that underscored by

the concept of precision medicine. The same physicians who say we already practice
personalized medicine are the first to admit we need more precise classification of
disease.
For a disease such as RA, many skilled physicians prefer the word syndrome over

disease, to emphasize this point exactly. RA is not one disease; rather, it is a collection
of distinct but overlapping diseases which make up a crude category we current call
rheumatoid arthritis.
Intuitively, most physicians believe that if we could understand these disease subsets,

then we could treat patients more effectively by picking the right medications (most of the
time, but not all of the time) and predicting the right outcomes (with greater precision).
In 2011, a group convened by the National Academy of Sciences published a 142-page

report entitled Toward Precision Medicine: Building a Knowledge Network for Biomedical
Research and a New Taxonomy of Disease. The new taxonomy that emerges would
define diseases by their underlying molecular causes and other factors in addition to their
traditional physical signs and symptoms.
The report adds that the new data network could also improve biomedical research by

enabling scientists to access patients information during treatment while still protecting
their rights.
This would allow the marriage of molecular research and clinical data at the point of care,

as opposed to research information continuing to reside primarily in academia.

REFERENCES

www.nih.gov/precisionmedicine

http://www.latimes.com/brandpublishing/localplus/ucsandiego/la-ss-ucsd2015-3dbioprinting-dto-story.html

http://www.cdc.gov/genomics/public/features/precision_med.htm

Francis S. Collins, M.D., Ph.D., and Harold Varmus, M.D. A, New Initiative on Precision Medicine, N Engl J Med 2015;
372:793-795 February 26, 2015 DOI: 10.1056/NEJMp1500523

Blau, CA, Liakopoulou, E (2013). "Can we deconstruct cancer, one patient at a time?".Trends in Genetics29(1): 6
10.

Levi A. Garraway, Jaap Verweij and Karla V. Ballman (2013). "Precision Oncology: An Overview".J. Clinical
Oncology31(15): 18031805.

Ogino S, Lochhead P, Chan AT, Nishihara R, Cho E, Wolpin BM, Meyerhardt AJ, Meissner A, Schernhammer ES, Fuchs
CS, Giovannucci E. Molecular pathological epidemiology of epigenetics: emerging integrative science to analyze
environment, host, and disease. Mod Pathol 2013;26:465-484.

Ogino S, Fuchs CS, Giovannucci E. How many molecular subtypes? Implications of the unique tumor principle in
personalized medicine. Expert Rev Mol Diagn 2012; 12: 621-628.

Ogino S, Lochhead P, Giovannucci E, Meyerhardt JA, Fuchs CS, Chan AT. Discovery of colorectal cancer PIK3CA
mutation as potential predictive biomarker: power and promise of molecular pathological epidemiology. Oncogene
advance online publication 24 June 2013; doi: 10.1038/onc.2013.244