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Defining cancers based on genetic ‘fingerprint’ could help personalise treatment

Doctors are closer to personalising treatment for some cancers as genetic analysis of tumours becomes more commonplace, according to research presented at the world’s largest cancer conference.

The goal of personalised, or precision, medicine is to select cancer treatment based on the genetic ‘fingerprint’ of each patient’s tumour.

In theory, selecting treatments in this way will make them more specific, which may then also lead to fewer side effects.

And several studies being presented at the 2016 ASCO conference in Chicago(link is external) highlight how DNA analysis is helping doctors offer more tailored treatment. 

The approach isn’t new, and some experts stressed that larger studies designed to prove its benefits were still needed.

The MyPathway study(link is external), led by scientists at the Sarah Cannon Research Institute in the US, gathered genetic data from 129 patients with different advanced cancers, including lung, bowel, bladder and ovarian. 

The patients’ tumours were tested for gene faults where a treatment that targets the fault exists but is not commonly offered for that type of cancer. 

For example, the drug vemurafenib (Zelboraf) is approved for treating melanoma skin cancers that carry a particular fault in the BRAF gene. But other tumours may also carry this fault, and may therefore be susceptible to the drug. 

As well as faults in the BRAF gene, the study also looked at the HER2, Hedgehog and EGFR genes, each of which have drugs available against them. 

Early results showed that of 118 patients who were followed-up, 29 saw their tumours respond to a matched drug in the 11 months following treatment. The responses were seen across 12 different types of cancer.

Professor Peter Johnson, Cancer Research UK's chief clinician, said that the early signs from this study were ‘positive’, and signalled a move towards defining tumours based on their DNA, rather than where they develop in the body.

"This is still early research,” he said. “But it shows that we’re starting to move from general treatments chosen on the basis of the tissue where the cancer starts and what the cancer looks like, to an era of molecular-designed therapy, targeting a tumour’s genetic fingerprint.” 

While personalised treatment and genetic tests are already available for some cancers, Johnson added that there was still work to be done to understand how the approach can be offered to all patients who need it.

“Cancer Research UK is developing targeted tests and treatments, particularly for lung and bowel cancer to help ensure the NHS is ready and able to adopt these new approaches to diagnose and treat cancer," he said.

But a recent Cancer Research UK report raised concerns that for cancers where targeted treatments and genetic tests are available, some NHS patients may be missing out.

A second study, from scientists at the University of California, San Diego and also presented at the conference, analysed data from published studies spanning over 13,200 patients enrolled in early-stage clinical trials.

The team found that studies using a personalised approach to treatment – where tumours were tested for genetic changes and matched to drugs – saw around a third of patients (31%) responding to therapy, compared to 5% in those applying a generic approach.

“This interesting analysis of earlier research shows that in some patients targeted drugs matched to molecular targets can work,” said Cancer Research UK’s Professor Johnson. 

“Cancers are complex and have many different abnormalities in their genes, so we need to fully understand how effective targeted treatments might be when compared with chemotherapy,” he added.

But personalising treatment requires access to DNA samples from tumours, which often involves an invasive tissue sample – or biopsy – that can be challenging in advanced cancers.

And experts believe that an alternative may be found in patient blood samples. 

The approach centres on how some tumours release pieces of their DNA into the bloodstream. 

These DNA fragments can be fished from blood samples and analysed. And many believe these so-called ‘liquid biopsies’ could offer a promising way of tracking a tumour’s genetic fingerprint without the need for invasive tissue samples.

third study(link is external) from scientists at the University of California Davis Comprehensive Cancer Center, including data from 15,000 advanced cancers, found that ‘liquid biopsies’ were as good as traditional tissue samples for picking up genetic faults found in tumours. 

Professor Jacqui Shaw, Cancer Research UK’s biomarker research expert from the University of Leicester, said the large analysis, including lung, breast, bowel and other cancers, confirmed the promise of liquid biopsies. 

She added that this approach “could one day transform how patients are monitored and treated”.

“Importantly in some cases, blood tests were better than tissue samples at identifying changes in genes that cause resistance to treatment,” she said. 

And in doing so these blood tests could help “identify patients who would benefit from tailored treatments that target genetic faults”.

While there is much excitement around the potential for ‘liquid biopsies’, experts also urged caution as large scale studies are still needed.

In a session discussing the potential for blood tests to help monitor patients’ tumours, Dr Melissa Johnson, from the Sarah Cannon Research Institute, said they “may be the stethoscope for next 200 years, but don’t take away my CT scan just yet". 

Cancer Research UK’s Professor Shaw also stressed that there was more to be done before these tests become a routine part of personalised treatment.

“This is important progress, but more research is needed before we see these blood tests being used to diagnose patients,” she said.

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