Technology Beats Cancer

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

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

Welcome

A transformational journey....

Hannah Foxley Founder of The Women’s Wealth Expert

The future of cancer treatment

James Hadfield Head of Genomics, Cancer Research UK

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

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”

Cancer: a disease of the genomes

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!

Many ways to sequence DNA

Cancer genomes

CRUK uses Illumina technology

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

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”.

Sequencing circulating tumour DNA

Sequencing circulating tumour DNA

Sequencing circulating tumour DNA

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

Understanding tumour evolution

Understanding tumour evolution

Understanding tumour evolution

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.

How does it all fit together: putative clinical workflows for genomic biomarkers

100ng Tumour DNA

Blood sampling

Biomarker analysis

Resected tumour Biomarker 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

Our genomes can be analysed

Our genomes can be analysed

“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

Personalised cancer genomics medicine

James Hadfield “It is essentially immoral not to get it [personalised cancer genomic medicine] done as quickly

as possible”

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

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