Personalized Health Care - University of Kentucky Chandler Medical ...

shamebagBiotechnology

Feb 22, 2013 (4 years and 5 months ago)

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To wrest from nature the secrets which have
perplexed philosophers in all ages, to track to their
sources the causes of disease, to correlate the vast
stores of knowledge, that they may be quickly
available for the prevention and cure of disease

these are our ambitions.

Sir William
Osler,
1849

1919

Father of Modern Medicine

All Surgical procedures are individualized
-

no two
cholecystectomies are identical



Medical treatment is tailored based on the patient's
family history, social circumstances, environment
and
behaviors of the individual

Personalized Medicine is not new….

Variation in Health care





















CANCER PATIENTS RECEIVING LIFE SUSTAINING PROCEDURE DURING THE LAST MONTH OF LIFE



Evidence Based Care


Based on epidemiological studies on large cohort

Framingham Heart Study

NSABP trial (National Surgical Adjuvant Breast and Bowel Project)

Cochrane reviews



Does not account for genetic variation within a population cohort
-

too general!






Why I need to know this?



“The great thing in this world is not so much where we
stand, as in what direction we are moving”


Oliver Wendell Holmes, 1809
-
1894

Physician, Poet and Writer



Single Nucleotide Polymorphism (SNP )

Only 1% of human genome has variation across individuals

SNP is a single base pair variant that appear in at least 1% of population

Estimated 10 million SNPs exist and can be correlated with disease

Efforts of SNP consortium and International HapMap Project


3.1
million SNPs as well as tag SNPs for disease association




www.genome.gov/GWAStudies

Biospecimen Banks


1.
Longitudinal population cohort banks
-

Group of individuals who are
representative of a population but not necessarily a disease. Example
Framingham Heart Study bank


2.
Clinical case/control banks
-

contain samples from studies in which a
population group with a particular disease is compared to a
demographically similar group that does not suffer from the disease


3.
Disease
-
specific biospecimen banks
-

Example NSABP biobank


Biobank



Played central role in Genomic Health’s Oncotype Dx testing service to
predict the risk of recurrence in early stage breast cancer patients .

Genomic Health refined its gene list and conducted two major validating
clinical studies of the test entirely on tissues banked by the NSABP



A similar opportunity now exists to refine prognosis and redirect treatment in
early stage lung cancer and a CALGB (Cancer and Leukemia Group B)
sponsored clinical trial (30506, NCT00863512) developed to use an
expression signature to randomize patients to surgical treatment with or
without adjuvant chemotherapy



World J Surg (
2009)

Model for development of personalized medicine

Personalized Surgery


Breast Cancer

BRAC1 and 2: Risk assessment of future Breast cancer and ovarian cancer

Oncotype Dx: Risk of recurrence, decision support tool for adjuvant therapy

Her2nu and
Transtuzumab

(
Herceptin
)


theranostics


Pancreatic cancer

microRNA

(diagnosis), HSP27 (prognosis),
Kras

(efficacy of chemo
-
Gemcetabine
),

TNF
erade

(immune therapy)


GI
Stromal

tumor
-

c Kit and
Imatinib

(
Gleevac
)


theranostics


Colorectal cancer

FAP testing, MMP2 (prognosis), micro satellite instability (response to 5FU),

Response Dx Assay and ColoPrint


Personalized Surgery…


Lung cancer

ERCC1 ,RRM1, EGFR(tailored chemo)

Response Dx (prediction of treatment response)

Ki67 , PIP3K/
mTOR



early detection , marker of dysplasia


Cardiovascular

9p21 as risk for CAD

Pharmacogenetics of
warfarin
,
clopidogrel
, anti hypertensive therapy, lipid
lowering therapy

Cyt

2C19
-

3 times risk of stent thrombosis



Personalized Surgery….


Trauma

GG ADRB2 genotype of autonomic receptors: 3
-
fold decrease in mortality odds

APOE
-
e4:TBI prognosis


Inflammation
-
wound healing

Biomarkers to predict wound healing

Molecular risk maps for IBD


Transplant

Pharmacogenetics of Tacrolimus

Complement associated SNP ( in addition of HLA matching)

Past and Present



Example



Present and Future



Example



Diagnosis


Disease
by Symptoms



High Blood Pressure


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Pr潧o潳楳o
-
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b礠䵥捨慮楳浳



Breast Cancer


HER2 Gene and
Oncotype Dx



Treatment
Guidelines


Disease Uniformity



Non
-
Hodgkin's
Lymphoma


Many
Cancers of Immune
System



Customized
Guidelines


Disease
Heterogeneity



Subclass of B
-
Cell
and T
-
Cell


Use of
Rituximab if CD
-
20
Positive



Patient Uniformity


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䑯獩湧


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䅮瑩c潡o畬u瑩潮o


浧⁰ 爠摡礠



Pa瑩敮琠t慲a慢楬i瑹t


Genetic
-
Guided
Dosing



Genotypes Defined
by 2C9 and
VKORC1


0.5 to 6
mg/day



Education …


CME
-

American College of Surgeons clinical congress 2011
-

Scientific
program


Targeted therapies


Biomarkers/Genetic Determinants of Disease and Outcomes


Critical Care : The Biology of Inflammation




Pay attention to Grand Rounds !


Future..


In coming years we will strengthen Evidence Based care and find ways to deliver
best standards in care. We will also be moving towards new molecular based
understanding of health and disease.


When these two vectors meet, we will develop ways to deliver the care that
works best on average but at the same time develop new tools for identifying
best care for individual patient.