FLG: Can you introduce yourself and your work?
I’m Dr Susie Cooke and I run the Glasgow Precision Oncology Laboratory, a high-throughput next-generation sequencing and bioinformatics cancer research facility at the University of Glasgow. We develop broad-spectrum genomic profiling assays and matching informatics pipelines and then use them to deliver molecular profiling for clinical trials. Our internally developed trials include Precision Panc, a UK-wide platform for pancreatic cancer, and IMAGINE (Integrating Medically Actionable Genomics Into Early-phase Trials), which will start to deliver genomic profiling for phase 1 trial patients in the West of Scotland. We also provide molecular profiling for multiple trials from Investigators across the UK and we support the roll out of our platforms (both wet and dry components) into labs that want to adopt and deliver them using their own local infrastructure. Currently we have our full workflow installed and working well as far afield as Verona, Italy, as well as sites in England and Scotland.
FLG: What motivated you to pursue a career in this field?
Purely because I found it interesting! I’ve never had a detailed plan of where I want to be in five or ten years’ time and how to get there – I just do the thing that feels most exciting at the time I’m looking. I did a PhD in breast cancer genomics and next-generation sequencing emerged when I was doing my first post-doc, so my career has grown with the sequencing technology and where it takes the field of cancer genomics. Having said that, since I started out, I have lost a lot of family members to cancer and that is what drives me to bridge the translation gap with my research. Too often cancer research stops with the theoretical benefits – how it could help patients – I think scientists (with funders’ support!) need to push harder to deliver those benefits, rather than just moving on to research the next big thing.
FLG: How do you think genetic testing/data is being used across the pharmaceutical industry today?
Genetic testing and data are being used in pretty much every way imaginable – risk stratification, screening, pharmacogenomics, diagnostics, precision therapeutics, disease monitoring. What is probably missing is consistency – making sure genetics/genomics are included for every study and every sample where it could be relevant, uniform workflows, comprehensive genomic profiling and analysis, integration with clinical meta-data and ultimately national and international data aggregation. Sometimes in the rush to leverage the power of genomics it can feel like we’re trying to do a jigsaw without turning all the pieces the right way up first – but it’s going to be confusing and end up taking longer if we don’t standardise and rationalise what’s being done, especially in healthcare delivery.
FLG: What sets the Glasgow Cancer Assay apart from others currently in use and what steps did you take in order to develop it?
There are two key features of the Glasgow Cancer Assays. Firstly, the evidence base behind the inclusion of each genomic feature – we did a meta-analysis of all publicly available data and literature, looking at all types of genomic alteration to work out which are the bone fide cancer genes, relevant signatures and non-coding features. We combined this with information on prevalence and utility to make sure that the assays cover the most clinically important genomic features for the largest number of cancer patients. Secondly, we’ve ensured that they generate equivalently robust data for all genomic feature types – copy number, structural changes and signatures, as well as the usual mutations and small indels – and we have a clinical-grade analytical pipeline that can analyse all those features. Copy number changes tell you at least as much about a cancer as mutations do, so it’s absolutely essential to assay and analyse both.
FLG: Why are we seeing an increase in the demand for genetic data in clinical development?
Simply because everyone is different and a lot of those differences are genetic. Similarly, every tumour is different and that’s down to how the cancer’s genome has evolved. Put together that means tumours respond differently to treatments and patients experience different side effects and we need to be able to predict both those elements and pick the right treatment for the right patient up front. There is a fundamental problem before we can reach the stage of picking and choosing treatments based on cancer genomics and pharmacogenomics though, and that is to get more treatments approved for cancer patients. At the moment, the clinical utility of genomic profiling for a cancer patient is limited because there aren’t that many treatment options. However, there is huge new/repurposed treatment and biomarker potential in the clinical trials space, we just need to realise that potential. Providing a broad genomic profile as standard would turn the entire cancer patient population into a trial-ready cohort for precision medicine, making drug development faster and economically viable, even for rare indications. It would be easier for patients to find trials and hence access state-of-the art therapies. Standard-of-care treatment options would improve more rapidly and we would be able to promise every cancer patient that we would learn from them to make it less likely that their friends, their children, their siblings will have to go through the same illness. Lower drug development costs would lead to lower drug prices and more competition and any healthcare system that rolled out comprehensive genomic profiling would attract investment from companies wanting to access patients for trials. It’s win-win-win for patients, public healthcare and pharma companies in terms of both economics and patient outcomes. Yet without it, we’re in complete deadlock in terms of therapeutic development and drug approvals. Seems like a no brainer to me!
FLG: What will GPOL be looking at turning its attention to next?
In 2020 we’ll be focusing on making our software more widely available. We’ll also be releasing more cancer assays – starting with one for haematological malignancies and an extended solid tumour panel called Cancer Plus that is designed for clinical trials use. The original Glasgow Cancer Assay – Cancer Core – focused on clinical utility and a price point compatible with use in resource-limited public healthcare systems. Cancer Plus includes more speculative genomic content and is based on horizon-scanning of what is coming through into the clinical trials space.
FLG: What do you think is the most exciting thing happening in genomics right now?
The most exciting thing in genomics right now is the opportunity to move it into clinical practice in a timely fashion. Genomics has never really been used in solid tumour clinical pathways before, so this would be a totally new strategy. As such, it has the potential to really disrupt how we manage cancer and therefore have an impact on outcomes. Cancer outcomes have been steadily improving over the last couple of decades, but the UK lags behind many other countries in cancer survival and 28% of us still end up with ‘cancer’ written on our death certificates. So, I think it’s time to try something new and keep the momentum going forwards – hopefully even accelerate progress.
FLG: What breakthroughs do you see happening in 12 months or 5 years?
Integrating genomics into routine oncology care pathways would be an ambitious but achievable goal for the next 12 months. That would be a breakthrough in terms of enabling the next wave of progress for cancer treatment and management strategies. I’m not sure I believe in ‘breakthroughs’ for cancer per se – there’s never going to be one single ‘cure for cancer’ but we will be able to work out how to deal with the disease one section of the patient population at a time. The progress that has been made for cervical cancer through effective screening and prevention through vaccination is a triumph and we’ll see that in incidence and outcome statistics over the next few years, but it obviously isn’t applicable to other tumours. I’m excited about immunotherapy, it definitely has the potential to provide long-term control of cancers for patients who might previously have been facing palliative care, but again it’s not going to work for everyone. We need to break the problem down and solve one piece at a time – that’s essentially what precision medicine will do.
FLG: Why are you speaking at the Festival of Genomics this year?
I think we’re reaching a critical point for cancer genomics – a lot of the discovery work has been done through initiatives like the International Cancer Genome Consortium (ICGC) and it’s at a stage where it could be usefully adopted into routine care pathways. However, there’s the risk of choosing the wrong path forward; we need to make sure we deliver the right genomics tests in the right way to maximise patient benefit and accelerate therapeutic development. This means moving away from thinking about genomics in a cancer type specific way. We can’t take the approach of saying ‘we need to test for these ten genes in this sub-type of cancer when these lines of treatments have failed’. We need to test all cancer-relevant genomic features in all advanced cancers as a reflex test at diagnosis. It means not taking a reactionary approach to genomic profiling by adding one gene at a time to test directories in response to a drug approval but instead rolling out a standardised and comprehensive genomic test for all advanced cancer patients. It means making an effort to ensure that we’re not biased towards point mutations for historical technical reasons but instead we use evidence of biological and clinical utility to make sure we’re assaying and analysing the genomic variants that are driving tumour development, treatment response and drug resistance. I want to be part of making sure we get it right first time. After all, for every year we wait or waste, 165,000 people in the UK will die of cancer.