The Landscape Of Personalized Medicine
Arwa Alhamed & Fahad Almsned
BINF704: Bioinformatics Colloquium
Bioinformatics and Computational Biology Department
School of Systems Biology
George Mason University
September 14, 2015
Outline
 Introduction and important milestones in PM’s journey
 PM in present day practice
 Relation to other disciplines
 Role in drug development
 Redefinition of traditional RCT
 Role in Disease prognosis
 Ethical considerations
 Key players in the development of personalized medicine
 Future of personalized medicine
 Benefits of personalized medicine’s impact on today’s medicine
 Personalized medicine limitation
 Conclusion
 References
Introduction
 Personalizing medicine?
 Shifting from traditional medicine
to PM.
o Increase in Knowledge
o Variations in response to therapy
PM In Present Day Practice
Personalized Medicine
 Medical model that proposes the
customization of healthcare - with
medical decisions, practices, and/or
products being tailored to the
individual patient. [1]
Important Milestones
[2]
1990
Official Launch of the Human Genome Project.
April 16, 1999
1st publication entitled “New Era of Personalized
Medicine—Targeting Drugs for Each Unique Genetic
Profile” by Robert Langreth and Michael Waldholz. [3]
2000
Human Genome Project have completed a rough draft
of the human genome. “the most important, most
wondrous map ever produced by humankind.”
Important Milestones [2]
2002
International HapMap project officially launches.
2003
The Human Genome Project is completed
2005
Cancer Genome Atlas project , publication of HapMap.
2008
GINA is signed into law
PM In Present Day Practice
PM In Present Day Practice
PM In Present Day Practice
Relation To Genetic Medicine
[4]
 The advancement in Genetic Medicine forms the basis of
PM.
 Distinct nature of the genome.
 Variations in the human genome.
 PM Vs GM.
Systems Biology and Pharmacology[5][6]
 Systems biology
 Developing tools to detect minute changes in molecular
profiles.
 Physiological environmental factors exposed to gene
expression.
 Systems Pharmacology
 Identity the genes and proteins responsible for drug
treatment.
PM In Present Day Practice
Biomarkers
[7]
 Biomarkers
• Measure indicators of the actual biology, disease or drug
response.
• Exist as proteins, DNA, mRNA, or radiological parameters.
• Applicable in areas of disease risk estimation, diagnostic
screening, diagnosis, prognosis, prediction, and response
monitoring.
Biomarkers [7]
 Biomarkers
 Used in determining dose size for clinical trials.
 Pharmacodynamics tests limitation.
 Biomarkers  maximum doses are determined by the presence
of specific biomarkers. (Reduction of Ki67 as a response to MEK
inhibitor)
Drug Development [8]
 Story of Trastuzumab
 30% of breast cancer patients unresponsive to SOC.
 Over expression of HER2 receptors.
Clinical Trail Design
[9]
 PM
 Redefining the traditional RCT.
 No control or placebo arms.
 Eliminate ethical concerns of using placebo.
Clinical Trail Design
[9]
 Most oncology drugs are approaching PM trial design
 Crizotinib  (ALK-EML4) inhibitor
 ALK-EML4 fusion is the driver for lung cancer progression
 Included 82 lung cancer patients tested positive for the
biomarker ALK with no control group.
 Favorable results as early as after 48 h with statistically
significant outcome as well.
Prognostic factor
 PM has facilitated genetic-based assessment.
 Abacavir hypersensitivity reactions.
 Traditionally, diagnosed after clinical manifestations of
symptoms.
 A study by Mallal et al.,[10]
 proved a genetic linkage between the hypersensitivity and HLAB*57:01.
 Upon investigation, patients who were tested negative for this
gene were not hypersensitive to abacavir and vice versa

Steering of both FDA and European Medicines Agency to require of
the pharmaceutical industries to include in their label precautions
the need to have gene testing prior to abacavir therapy.
Prognostic factor
Ethical considerations
[11]
 Primarily concern the protection of genetic information
and other private information of participating
individuals.
 In the US, the Genetic Information Nondisclosure Act
(GINA) ensures the ethical use of genetic information.
 The focus is on obtaining approval for the molecular diagnostic
tests and the drugs related to the PM.
 FDA encourages but does not make it mandatory to submit
pharmacogenetic and pharmacogenomic data during the drug
development.
Key Players in the Development of
Personalized Medicine
 Industrial players: pharmaceutical and biotechnology
companies; Hoffman-La Roche.
 Academic institutions; Pfizer/Harvard Medical School,
Perlegen/George Washington University and Pathway Diagnostics/Duke
University.
 Scientific players:
 Clinical laboratories; Genomas ®.
 Health Information Technology (HIT); The Cancer Biomedical
Informatics Grid.
 Medical professions.
 Political, and socioeconomic players; Personalized Genome
Project.
Future of Personalized Medicine
Future of Personalized Medicine
 Genomic projects
 Translational Science and medicine, and personal genetic
testing.
 Conventional medicine evolution to personalized medicine
1. Genomic Projects
 Molecular diagnostic of breast cancer, 2005.
 Personal Genome Project
 Genome-Wide Association Studies (GWAS)
 1000 Genome Project
2. Translational Science and Medicine, and
Personal Genetic Testing
 Biomarkers, animal models, bioinformatics, and image
analysis software.
 Long-term genetic testing.
3. Conventional Medicine Evolution to
Personalized Medicine
 Increasing genomic knowledge.
 Safer and cost-effective medications; Genomics
Personalized Medicine Act of 2006.
Benefits of Personalized Medicine’s
Impact on Today’s Medicine
 High precision effective and low-cost treatment; metastatic
colorectal cancer
 Improving quality of life for healthy and patient individuals.
 Avoiding trail-and-error approach used by physicians in the
diagnosis and the treatment of a disease.
 Lowering drug development cost and time; Ellen Roche’s death
 Attribution to the discovery of new safer and more effective
treatments in the market.
 “hope rescue failed drugs”; saving drugs which worked for
particular health cases.
Personalized Medicine’s Limitation
 Common diseases’ treatment personalization.
 Environmental factors’ impact on drug response.
 Government and healthcare institution support
shortage; data entries in developed countries vs. third world
countries.
 Legal, ethical, and social issues; Verisante.
 “Incidentalome”.
Conclusion
 Stakeholders
 Patient
 Physicians
 Medical Practice
 Pharmaceutical and biotechnology companies
 Regulatory authorities
 Government and healthcare agencies
Personalized medicine stands a promising chance of
overtaking conventional medicine in the future, but
couldn’t totally rule it out..
References
1.
"Personalized Medicine 101". Personalized Medicine Coalition. Retrieved 26 April 2014.
2.
https://hms.harvard.edu/news/harvard-medicine/expanded-timeline-personalized-medicine
3.
Langreth R, Waldholz M. New era of personalized medicine: Targeting drugs for each unique genetic profile.
The Oncologist 1999;4:426-427
4.
Jain KK. Netherlands: Springer Science+Business Media; 2009. Textbook of Personalised Medicine.
5.
Chen R, Snyder M. Systems biology: Personalized medicine for the future? Curr Opin Pharmacol. 2012;12:623–
8.
6.
Wist AD, Berger SI, Iyengar R. Systems pharmacology and genome medicine: A future perspective. Genome
Med. 2009;1:11.
7.
Kennedy R. Biomarkers and Personalised Medicine. 2013.
8.
Feinstein Kean Healthcare. What is Personalized Medicine?; 2013.
9.
Vaidyanathan G. Redefining clinical trials: The age of personalized medicine. Cell. 2012;148:1079–80.
10.
Mallal S, Phillips E, Carosi G, Molina JM, Workman C, Tomazic J, et al. HLA-B*5701 screening for
hypersensitivity to abacavir. N Engl J Med. 2008;358:568–79.
11.
Jain KK. Netherlands: Springer Science+Business Media; 2009. Textbook of Personalised Medicine.
Any Questions?
Thank You For Listening!
Arwa Alhamed and Fahad Almsned
Bioinformatics and Computational Biology Department
School of Systems Biology
George Mason University