With the potential of personalised medicine becoming ever clearer, clinicians are increasingly turning their attention to the various ways in which this can be realised, and genomics is a prime example of where huge progress can be made. Consultant in medical oncology Dr Nirupa Murugaesu discusses how the 100,000 Genomes Project has supported both research and service delivery in the UK and how whole genome sequencing can be harnessed to transform cancer care.
In October 1990, some of the best scientific brains in the world began working on an international programme to sequence an entire human genome. It took 10 years to complete an initial sequence and cost billions of US dollars.
Fast forward to today, and the picture is vastly different. ‘Because of next-generation sequencing and advances in technology we are now able to sequence a genome comprising around 20,000 genes in less than a week, at a fraction of the cost,’ says Dr Nirupa Murugaesu, consultant in medical oncology and cancer genomics lead at London’s Guy’s and St Thomas’ NHS Foundation Trust.
‘We can now see how routine sequencing to understand the mutational landscape of cancers has helped in terms of understanding more how the cancer is likely to behave, and also determining the best treatment approaches for patients.’
Dr Murugaesu is also principal clinician in cancer genomics and clinical studies at Genomics England. The organisation has been collaborating with NHS England, Queen Mary University of London and the University of Westminster on research into how whole genome sequencing can be combined with clinical data from patients to identify changes in in their cancer’s DNA.
The study, published earlier this year in the journal Nature Medicine, involved more than 13,000 participants with solid mass tumours, and examined clinicopathological data – their type of cancer, histological subtype, the behaviour of their tumour, the types of treatment and survival – over a five-year period.
By combining that information with genomic data, the researchers could pinpoint the cancer’s genetic changes and mutations that resulted in different outcomes. Crucially, this can improve precision cancer care, meaning therapies can be better targeted and individualised to each patient.
Participants were recruited as part of the UK’s 100,000 Genomes Project, which has also collected and analysed data on a number of rare diseases. The solid cancer study found that, through whole genome sequencing, clinicians can use a single test to uncover genetic changes in a tumour.
Implementing genomics findings in practice
What sets this study apart from other research in genomics is that, for the first time, the information collected could be applied in real-world settings and in real time, Dr Murugaesu explains.
‘The unique selling point was to have a research study that is embedded within a healthcare system. After the genomes were sequenced, the results were in fact returned to the respective hospital trusts and treating clinicians,’ she says.
‘Normally when research is carried out, the results are not necessarily fed back. We have clinical trials and outcomes that do not always reflect what we end up seeing in practice. But here, we have that real-world clinical information linked with patients’ genomic data, so if there were relevant findings that could be acted upon, this could be undertaken by the treating clinical team.’
Currently, this can be applied in healthcare settings and influence how cancer patients are treated. In particular, it may be helpful in knowing which treatments are less likely to work, or which may not be necessary. ‘If we know from the data that a person’s tumour is likely to be less aggressive, we can decide to not overtreat them, and we can give less-toxic therapies,’ Dr Murugaesu says.
In addition, clinicians can provide patients with more information about how their cancer is likely to behave and what their prognosis may be. In the future, as more data are accumulated and genomics research progresses further, they may be used to develop new and improved therapies as well.
Equitable access to genomic testing
Having laid the groundwork for genomic testing in England, the 100,000 Genomes Project has led to a Genomic Medicine Service being developed and rolled out nationwide.
As a result, Dr Murugaesu says there are criteria for ensuring that minimum standards are met for testing different cancer types, and, importantly, that testing is provided equitably across the country, rather than only at larger cancer centres.
Enormous progress has been made from the early shoots of genomics, when sequencing took years and had a hefty price tag, to becoming embedded into routine care. Now, however, training and education must keep pace with the science, Dr Murugaesu explains.
‘It is now about upskilling the workforce – not just oncologists, but the whole multidisciplinary team – so they understand the role of genomics, and that there is a Genomic Medicine Service available to their patients,’ she says.
In addition, infrastructure and pathways must be set up efficiently to ensure that when a patient undergoes genomic sequencing, their results are returned to their treating team in a timely manner. If genomic testing is performed alongside a biopsy to confirm a cancer diagnosis, and taking that as Day 1, the goal is to have the results back by Day 14, Dr Murugaesu says.
‘That is a challenge that’s not consistently being met, but work is ongoing and one of the main focuses over the next year will be to try and understand the bottlenecks so we can streamline these pathways,’ she adds.
Expanding genomics testing and potential
Other technology will have a role in supporting enhanced learning about the genomics of cancer, too. A case in point is liquid biopsies, whereby a blood sample can enable the extraction of circulating tumour DNA – which is shed by tumours, especially those that are more advanced – and sequencing of that DNA can then be undertaken, just as you would for a genomic panel. ‘The repertoire is expanding for what is available and possible to fully molecularly profile tumours,’ Dr Murugaesu says.
Again, performed as soon as there is radiological suspicion of cancer, a simple blood sample can enable genomic sequencing of the tumour’s circulating DNA. If successful, this testing can potentially circumvent problems associated with tissue biopsies, such as not getting enough tissue to yield meaningful results. This has implications for patients – needing to go through the upheaval of a repeat biopsy, for example – and places resource and time pressures on healthcare systems.
A pilot exploring this technology in non-small cell lung cancer is currently under way and has demonstrated promising results in the initial phase.
‘The next phase has now launched and there will be 10,000 tests made available across England for patients with suspected lung cancer, which is exciting because there’s a real opportunity to expand our circulating tumour DNA testing,’ Dr Murugaesu says. ‘There is more and more emerging data about what the role of circulating DNA may be, including screening and earlier detection of cancers.’
There is interesting work in genomic testing across Europe, too. For example, scientists at The Hartwig Medical Foundation in Amsterdam found clinically relevant data from almost 5,000 metastatic solid tumour samples, and supported recruitment to a large-scale trial in the Netherlands – the Drug Rediscovery Protocol (DRUP) trial.
The study is collecting information on the off-label use of registered targeted therapies for patients with incurable cancer who have exhausted standard treatment options, based on their tumour’s molecular profile.
This is one way of embedding genomic testing into cancer care. Dr Murugaesu hopes this becomes routine in the future so that not only will whole genome and genomic panel sequencing help predict the best therapies, but also it could identify whether patients are at increased risk of their cancer reoccurring.
There is enormous potential for genomic medicine to take much of the guesswork out of how tumours are treated, and to be truly transformative in cancer care globally.
