The document discusses the Precision Medicine Initiative (PMI) and Cancer Moonshot program. PMI aims to tailor medical treatment to individual characteristics like genes and lifestyle by collecting health data from 1 million volunteers. Cancer Moonshot seeks to accelerate cancer research advances by 5 years through tumor mapping, new technologies, data sharing, and engaging patients. Challenges include genetics not explaining all disease, tumor heterogeneity, and defining success. Precision medicine could reduce ineffective treatments and costs while advancing scientific understanding of disease.

1. 1
The Precision Medicine Initiative
and “Cancer Moonshot”
Jonathan J. Darrow
Instructor in Medicine
Harvard Medical School
Brigham & Women’s Hospital
January 23, 2017
RedactedRedacted

2. 2
Precision Medicine Initiative (PMI):
Launch
• PMI announced Jan. 20, 2015: State of the Union
Redacted

3. 3
What Is “Precision Medicine”?
• Traditional approach: “one-size-fits all”
• PMI: “takes into account individual
differences in … genes, environments,
and lifestyle.”*
– Theoretically, also about
• proteome, microbiome, metabolome, transcriptome,
lipidome, epigenome, exposome…
*https://www.whitehouse.gov/the-press-office/2015/01/30/fact-sheet-president-obama-s-precision-medicine-
initiative

4. 4
What is the PMI?
• NIH “All of us” program
– longitudinal cohort study
– 1,000,000 people volunteer health data
Redacted

5. 5
Cancer Moonshot
• 2016 State of the Union address
– Jan. 28, 2016: “Cancer Moonshot” Taskforce
is established
– Headed by VP Biden
• Also, heads of: NCI, NIH, FDA, DoD, DoC, DHHS,
DoE, VA, OMB, OST, NSF…
• Aim of Moonshot:
– “10 years worth of advances in 5 years”

6. 6
Moonshot Target Areas (selected)
• Prevention, early detection
– HPV vaccination, tobacco control, cancer screening (e.g., genetic,
colonoscopy)
– Develop preventive immunotherapies / vaccines
• Map the evolution of human tumors (“Tumor Atlases”)
• Develop new cancer technologies
– imaging, intra-tumoral microdosing, better cancer models
• Retrospective analyses of tumor samples
– generate hypotheses, e.g., gene-outcome relationship
• Network for direct patient engagement
– large scale tumor profiling
– “pre-registration” for clinical trials
• Data sharing
– Create national cancer data “ecosystem”
– Collaboration across organizations / industry
• “Symptom management”
– e.g., patient-reported outcomes via cell phones
See Jacks T et al. Cancer moonshot blue ribbon panel report. 2016.

7. 7
Why Now?
• 1971 Nixon announces “War on
Cancer”
• Since then:
– 1983 Polymerase chain reaction
– 1990s Explosion of information
technology
– 2003 Human Genome Project
completed
– 2010s Push to use Electronic Health
Records
Redacted

8. 8
Redacted

9. 9
Exercise
Diet
Smoking
Other
CHALLENGE #1:
Genetics are not “all-important”
Genetics
See: Rappaport SM. Genetic Factors Are Not the Major Causes of Chronic Diseases. PLoS ONE Apr. 22, 2016.
See: Wu S et al. Substantial contribution of extrinsic risk factors to cancer... Nature 2016; 529(7584):43–7
See: Ehret GB et al. Genetic variants in novel pathways... Nature 2011;478:103-09.
Hypothetical
contribution to
disease burden

10. 10
CHALLENGE #2:
Tumor Heterogeneity
Source: Gerlinger M et al. Intratumor heterogeneity and branched evolution revealed by
multiregion sequencing. NEJM 2012;336(10):883-92.
Redacted

11. 11
Challenge #3:
What Is Success?
“Twenty-first century businesses will rely on American science
and technology, research and development. I want the country that
eliminated polio and mapped the human genome to lead a new era
of medicine ̶ one that delivers the right treatment at the right time.
(Applause.)
In some patients with cystic fibrosis, this approach has reversed a
disease once thought unstoppable. So tonight, I’m launching a
new Precision Medicine Initiative to bring us closer to curing
diseases like cancer and diabetes, and to give all of us access to the
personalized information we need to keep ourselves and our
families healthier. We can do this. (Applause.)”
- Barack Obama, State of the Union (2015)

12. 12
RedactedRedacted
Redacted

13. 13
DOCTORS
DELIVER
RIGHT
TREATMENT
AT RIGHT
TIME
Washington Times
Redacted
Redacted

14. 14
Source: Mennel RG. Precision
medicine: hype or hope? Proc
(Bayl Univ Med Cent)
2015;28(3):397-400 (original
image from Abcam).
Redacted

15. 15
Conclusion:
The Promise of Precision Medicine
• Patients: Reduce unhelpful treatments
– E.g., cetuximab (Erbitux) is not effective in those with
KRAS mutation
– save (1) cost, (2) time, (3) side effects
• Industry: Less costly clinical trials
– larger efficacy smaller clinical trials
– fewer trial failures
• Science: New taxonomy of disease
– E.g., rather than defining cancer by the part of the
body (“lung cancer”), define by genetic/molecular
mechanism.