Precision medicine is at the forefront of innovative cancer treatment, targeting specific changes in a patient’s tumour DNA to treat, or even maybe one day prevent, the disease while also taking into account genetic variations between individuals, along with environmental and lifestyle factors.
Precision medicine is an alternative strategy to some of the one-size-fits-all approaches of older cancer treatments, which often have harsher side effects, and aims to maximise the likelihood that treatment will be effective by identifying those patients likely to respond.
A precision medicine mind-set in cancer drug discovery
At the start of December last year, The Institute of Cancer Research, London, was awarded a highly prestigious Queen’s Anniversary Prize for its pioneering discoveries in precision medicines for cancer, having discovered 20 new potential targeted cancer drugs and now taken ten into clinical trials since 2005.
During the panel session at The Economist's ‘War on Cancer’ event, Dr Olivia Rossanese discussed the importance of incorporating precision medicine ideas into drug discovery.
“Precision medicine means that drug discovery is not just coming up with the drug, it’s also coming up with a therapeutic hypothesis, understanding which patients will respond and why, and finding a way to identify those patients.
“This includes the delivery of a drug, a biomarker of response and a diagnostic tool that can find the right patients.”
Applying precision medicine to current treatments
Dr Rossanese emphasises the need for a personalised component in all types of treatments, even immunotherapy.
“All aspects of cancer medicine – including diagnoses, chemotherapy and immunotherapy – need some element of precision to stratify who will respond and which treatment is the best option,” she explained.
“For example, measuring the number of immune cells that infiltrate a tumour would allow a person’s predicted response to immunotherapy to be assessed and accounted for.”
Precision medicine could also be used as an early marker of resistance to therapy or of disease recurrence; detecting biomarkers or specific genetic changes in the blood could signal a change in response to therapy and allow for decisions regarding treatment to be made earlier.
“This precision approach will allow for continuous learning to be incorporated into the next round of treatment and, ultimately, the next generation of drug discovery or diagnostic tools.”
In 2016, the ICR launched a bold and ambitious five-year joint research strategy with The Royal Marsden NHS Foundation Trust that will speed up our progress against cancer.
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The role of biomarkers in precision medicine
This use of biomarkers in precision medicine for the treatment of cancer can be seen in the development of BRAF inhibitors, an area that Dr Rossanese has worked extensively in.
In the early 1990s, a team of ICR researchers led by Professor Chris Marshall predicted that a gene called BRAF played a role in cancer development. Working alongside colleagues at The Wellcome Trust Sanger Institute to investigate this hypothesis further, Professor Marshall’s team, along with ICR researcher Professor Richard Marais found that BRAF mutations not only present in a number of cancers, but are capable of driving the development of cancer even in the absence of other major genetic defects.
As a number of cancers stem from mutations in a gene called BRAF, anti-cancer drugs that specifically inhibit this gene have been developed. When ICR researchers, Professors David Barford and Richard Marais elucidated the detailed molecular structure of the mutated gene, pharmaceutical companies, such as the one Dr Olivia Rossanese was working at, were able to develop selective inhibitors of mutated BRAF – including vemurafenib and dabrafenib.
Therefore, BRAF-V600E can be used as a biomarker to determine how well a patient with one of these cancer types will respond to drugs that specifically target it.
Encouraging innovation in precision
Despite all the progress made so far in targeted cancer drug discovery, particularly at the ICR, Dr Rossanese explained that the ability to identify and measure mutations or drivers in patient tumours has out-paced drug discovery efforts to come up with individual medicines to target each of these drivers.
It is tempting, especially for pharmaceutical companies, to follow in the footsteps of previously successful drugs, resulting in over-investment in ‘me-too’ drugs instead of innovative new drugs.
Dr Rossanese explained:
“It is hard to define innovation without knowing what the next big thing will be, or what will lead to the next breakthrough. But it is important to discourage researchers from expending too much effort jumping on the band-wagon of ‘me-too’ drugs and to encourage the development of unique drugs.”
One way to combat this ‘me-too’-ism and incentivise innovation is to introduce a law, as is already in place in some countries, which prevents companies from charging as much for me-too drugs as the original, first-of-its-kind treatment.
For example, regulators in countries including Germany, Hungary and New Zealand only allow me-too drugs to be admitted for reimbursement from their national health service if they are cheaper than the originator drug, or contain significant therapeutic improvements.
This active management still allows follow-on drugs with proven benefits to reach the patient, but also encourages the development of innovative drugs.
Patient-centricity for precision medicine
For precision medicine to succeed, patient-centricity is essential – not only do we need nation-wide access to the treatments, drugs and care but also to the diagnostic tools and genetic tests, which are enhanced by increased sharing of health data throughout the UK.
By identifying biomarkers associated with patient responses to treatment, clinical trials can be designed around the individual patients. These hypothesis-driven trials are cheaper due to their biomarker-based design and, combined with increase routine patient-reported outcome measurement, will improve drug reviews and lead to faster drug approval rates.
If achieved, this could reduce the time it takes for a drug to get from bench to bedside, increasing a patient’s access to potentially life-saving drugs.
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