The document discusses advances in genomic sequencing technology and its potential to revolutionize cancer treatment. James Hadfield of Cancer Research UK describes how sequencing costs have plummeted from $3 billion for the first human genome to $1,000 per genome today. Next-generation sequencing is enabling analysis of cancer genomes and monitoring of tumor evolution during treatment. Hadfield argues that personalized cancer genomic medicine, using sequencing to tailor treatments to individual patients' tumor mutations, should be implemented as quickly as possible, as it represents the most significant change in cancer care since chemotherapy.

1. Technology Beats Cancer
Tuesday 14th May, 2013
Eight Club, Bank

2. Robert Gardner
Board Member, The Catalyst Club
Founder & Co-CEO, Redington
Welcome

3. A transformational journey....
Hannah Foxley
Founder of The Women’s Wealth Expert

4. The future of cancer treatment
James Hadfield
Head of Genomics, Cancer Research UK

5. The Catalyst Club 2013
Core Genomics blog: http://core-genomics.blogspot.com
The GoogleMap of NGS: http://omicsmaps.com
James.Hadfield@cruk.cam.ac.uk
Personalising cancer medicine
one genome at a time

6. The Human Genome Project
$3 billion and 15 years…for one genome
James Watson “It is essentially immoral not to get it
[the Human Genome Project] done as quickly as possible”

7. Cancer: a disease of the genomes

8. Moore’s law
Moore’s Law” -- Proposed by Gordon Moore, co-founder of Intel, this law accurately projected that the transistor count on a microchip
would nearly double every two years. By extension, performance of computing would also double ever two years at similar costs. Four
decades later, transistor count has grown by a factor 105 and silicon technology has seeped into every aspect of our lives.
“Metcalfe Law” -- Attributed to Robert Metcalfe, co-inventor of Ethernet and founder of 3Com, this law proposes that the value of a
telecommunications network is proportional to the square of the number of connected users of the system. While a slightly obtuse
definition, in essence it suggests that the value of a network increases exponentially as you add more people to it.
Think Facebook, Twitter, and now Instagram!

9. Many ways to sequence DNA

10. Cancer genomes

11. CRUK uses Illumina technology

12. CRUK Stratified Medicine
• Currently around 60 clinical tests (10 with clinical
utility in drug testing) on 5-10,000 patients per year
• Potential: BrCA54000, PrCa36000, OvCa6000, PaCa7000
(UK cases per year)
• 100,000 cases but which tests and how?
• Stratified Medicine Project: Sample collection,
Sample Prep, Throughput, Analysis, Ethics
• >2500 patients, 815 sets of cancer gene test
results
• 95% of patients agree to take part
• Current Sanger sequencing will be supplanted
by Next-Generation Sequencing

13. Resected
tumour
Biomarker
discovery
Next-gen
sequencing
data
Blood
sampling
Biomarker
analysis
• Aim to identify an individuals tumour mutations for treatment and follow-up
decisions.
Personalised Genomic Medicine
• Biopsies are invasive and costly, provide a snapshot of mutations.
• Plasma DNA could be used as a “liquid biopsy”.

14. Sequencing circulating tumour DNA

15. Sequencing circulating tumour DNA

16. Sequencing circulating tumour DNA

17. Resected
tumour
Biomarker
discovery
Next-gen
sequencing data
Blood
sampling
Biomarker
analysis
• The technology exists to analyse a few genes in Cancer patients
today…
• …what can we do tomorrow?
Personalised Genomic Medicine

18. Understanding tumour evolution

19. Understanding tumour evolution

20. Understanding tumour evolution

21. Understanding tumour evolution
Case 1 BrCA: After paclitaxel treatment an increase in the levels of a PIK3CA mutation,
these mutations are known to be involved in paclitaxel resistance.
Case 2 BrCA ER+, Her2+: After tamoxifen + trastuzumab treatment an initial increase in
the levels of a MED1 mutation, this is an ER co-activator and these mutations are known
to be involved in tamoxifen resistance. After secondary therapy with lapatinib +
capecitabine a mutation in GAS6 was linked to activation of the AXL tyrosine-kinase
receptor which is known to be involved with lapatanib resistance.
Case 4 OvCA: After cisplatin treatment an increase in the levels of a RB1 mutation, which
was also seen in 95% of reads from the metastatic biopsy. RB1 loss is known to be
involved in chemotherapy resistance.
Case 6 NSCLC: After gefitinib treatment an EGFR mutation was detected with digital-PCR,
this mutation is known to inhibit binding of gefitinib to EGFR and is the main driver of
gefitinib resistance.

22. How does it all fit together: putative clinical
workflows for genomic biomarkers
100ng Tumour DNA
Blood
sampling
Biomarker
analysis
Resected
tumourBiomarker discovery
Biomarker discovery
Amplicon-seq
COSMIC cancer mutation amplicon screen
Exome-seq
Clinical Exome-seq by Nextera:capture
Genome-seq
Whole genome sequencing from Nextera library
Exome-seq
TAm-seq

23. Our genomes can be analysed

24. Our genomes can be analysed

25. “Genome in day” machines
HiSeq 2500 Ion Proton
Company Illumina Life Technologies
Max read length (insert) PE150 (1200bp) PE200 (400bp)
Genome in a day $$$ $1000 $1000
Genome in a day hr:mn 24hour 2.5hour
Data output 60Gb 10-100Gb

26. Personalised cancer genomics medicine
James Hadfield “It is essentially immoral not to get it
[personalised cancer genomic medicine] done as quickly
as possible”

27. ‘Personalised medicine is the most exciting
change in cancer treatment since the
invention of chemotherapy’
Professor Peter Johnson, Chief Clinician, Cancer Research UK

28. Technology Beats Cancer
Tuesday 14th May, 2013
Eight Club, Bank