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”
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!
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
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
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
