The Landscape Of Personalized Medicine

Arwa Alhamed & Fahad AlmsnedBINF704: Bioinformatics Colloquium

Bioinformatics and Computational Biology DepartmentSchool of Systems BiologyGeorge 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

IntroductionPersonalizing medicine?

Shifting from traditional medicine to PM.o Increase in Knowledgeo Variations in response to

therapy

PM In Present Day Practice

Personalized MedicineMedical 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, 19991st publication entitled “New Era of Personalized

Medicine—Targeting Drugs for Each Unique Genetic Profile” by Robert Langreth and Michael

Waldholz. [3]

2000Human Genome Project have completed a rough draft of the human genome. “the most important,

most wondrous map ever produced by humankind.”

Important Milestones [2]

2002International HapMap project officially launches.

2003The Human Genome Project is completed

2005Cancer Genome Atlas project , publication of

HapMap.

2008GINA 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]

BiomarkersUsed 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 Trastuzumab30% 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 factorPM 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.

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 MedicineGenomic 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..

References1. "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 AlmsnedBioinformatics and Computational Biology

DepartmentSchool of Systems BiologyGeorge Mason University