1. 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

2. 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

3. Introduction Personalizing medicine?
Shifting from traditional medicine to PM.
Increase in Knowledge
Variations in response to therapy

4. PM In Present Day Practice

5. Personalized Medicine
Medical model that proposes the customization of healthcare - with medical decisions, practices, and/or products being tailored to the individual patient. [1]

6. 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.”

7. 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

8. PM In Present Day Practice

9. PM In Present Day Practice

10. PM In Present Day Practice

11. 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.

12. Systems Biology and Pharmacology[5][6]
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.

13. PM In Present Day Practice

14. 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.

15. 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)

16. Drug Development [8] Story of Trastuzumab
30% of breast cancer patients unresponsive to SOC.
Over expression of HER2 receptors.

17. Clinical Trail Design [9]PM
Redefining the traditional RCT.
No control or placebo arms.
Eliminate ethical concerns of using placebo.

18. 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.

19. 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 HLA- B*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.

20. Prognostic factor

21. 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.

22. 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.

23. Future of Personalized Medicine

24. Future of Personalized Medicine
Genomic projects
Translational Science and medicine, and personal genetic testing.
Conventional medicine evolution to personalized medicine

25. 1. Genomic Projects Molecular diagnostic of breast cancer, 2005.
Personal Genome Project
Genome-Wide Association Studies (GWAS)
1000 Genome Project

26. 2. Translational Science and Medicine, and Personal Genetic Testing
Biomarkers, animal models, bioinformatics, and image analysis software.
Long-term genetic testing.

27. 3. Conventional Medicine Evolution to Personalized Medicine
Increasing genomic knowledge.
Safer and cost-effective medications; Genomics Personalized Medicine Act of 2006.

28. 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.

29. 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”.

30. Conclusion Stakeholders Patient Physicians Medical Practice
Pharmaceutical and biotechnology companies
Regulatory authorities
Government and healthcare agencies

31. Personalized medicine stands a promising chance of overtaking conventional medicine in the future, but couldn’t totally rule it out..

32. References
"Personalized Medicine 101". Personalized Medicine Coalition. Retrieved 26 April 2014.
Langreth R, Waldholz M. New era of personalized medicine: Targeting drugs for each unique genetic profile. The Oncologist 1999;4:
Jain KK. Netherlands: Springer Science+Business Media; Textbook of Personalised Medicine.
Chen R, Snyder M. Systems biology: Personalized medicine for the future? Curr Opin Pharmacol. 2012;12:623– 8.
Wist AD, Berger SI, Iyengar R. Systems pharmacology and genome medicine: A future perspective. Genome Med. 2009;1:11.
Kennedy R. Biomarkers and Personalised Medicine
Feinstein Kean Healthcare. What is Personalized Medicine?; 2013.
Vaidyanathan G. Redefining clinical trials: The age of personalized medicine. Cell. 2012;148:1079–80.
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.

33. Any Questions?

34. Thank You For Listening!
Arwa Alhamed and Fahad Almsned
Bioinformatics and Computational Biology Department
School of Systems Biology
George Mason University