How far are we from the vision of precision medicine that is so commonly presented to us?
Writer: Sumayyah Imran
Editor: Skyla (Wingyan) Siu
Artist: Zach Ng
For the past few years, I have been as captivated by the prospect of precision medicine as the rest of the public and the scientific community. However, upon researching the field I discovered that, as with so many other technologies intended to revolutionise healthcare, there is a significant chasm between the promise of precision medicine and its implementation. So where do we stand? What are the issues, and what does the future hold? Can we still see a future for this approach?
Precision medicine is defined as the adaptation of medical treatment to a patient’s lifestyle and genotype. The logic behind it is simple; at present, the ‘one size fits all’ approach to medical care fails to account for individual variations in genetics and environment. Precision medicine will allow clinicians to match their patients to appropriate treatments on the basis of both clinical factors and molecular biomarkers. This will limit exposure to ineffective and potentially harmful drugs and maximise the time for which patients receive beneficial treatment.
Tumour profiling and pharmacogenomics are two avenues that are being explored.
Genetic profiling of tumours focuses on identifying mutations that drive cancer development and can act as potential drug targets. This has created a new buzz in oncology, and since the early 2000s, when trastuzumab was approved for breast cancer expressing HER2 receptors, there has been a race to develop drugs acting on a range of tumour biomarkers.
Pharmacogenomics develops therapies targeted to particular alleles that influence drug uptake, distribution and metabolism. A number of drugs which come with companion diagnostics have been approved by the US Food and Drug Administration (FDA). These are only to be used if patients are genetically compatible with them. For instance, the HIV drug abacavir and the anti-seizure drug carbamazepine are known to cause serious side effects in patients with certain HLA gene variants.
It is clear that precision medicine holds exciting promise for the future. This has been latched onto by the academic community and the public alike, fuelled by media reports and economic incentives like Barack Obama’s $215 million Precision Medicine Initiative. However, the pace of development seems to be outstripping the evidence.
Academic interest in precision therapies for cancer was catalysed by a series of case reports of super-responders to these treatments. However, a systematic review of these reports revealed several shortcomings in the data. It appears that much of the optimistic discourse stems from incomplete evidence which cannot be generalised to the broader population. Furthermore, the few randomised controlled trials which have been conducted into precision cancer therapies have yielded modest results at best and poorer treatment tolerance at worst. These studies demonstrate the need for pragmatism; much of the academic community is jumping the gun before appropriate evidence can be obtained.
Precision pharmacotherapy has three main problems. Firstly, the demand for therapies currently outstrips the available treatments. Secondly, trials target a narrow patient population, which limits drug indications. Finally, there is very little gold-standard testing of the drugs. Considerable amounts of time and funding are required to overcome these issues.
Other barriers to adoption
Practicality and logistics pose the most obvious issue. Precision medicine requires the integration of various streams of data, from blood results to gene profiles, and thus has complex data needs. It is here that artificial intelligence (AI) may play a role. However, this requires high-quality input data, which we don’t always have access to.
There are also significant ethical concerns associated with precision medicine. Most research into the discipline is conducted at large academic centres in developed nations, and this does not translate well into rural or resource-deprived settings. Funding and resource barriers, coupled with many clinicians’ lack of awareness of the available treatments, will undoubtedly lead to huge inequities in care delivery. The issue of inclusion doesn’t end there; the majority of available genetic data has been taken from individuals of Northern European origin and is thus unlikely to account for variants in people of different ethnic groups. Indeed, genetic test results indicating a ‘variant of unknown significance’ are of greater frequency in ethnic minority women, and this is testament to how under-researched the interests of these patient populations are.
What can be done to make the promises of the past decades a reality?
Firstly, the scientific community must commit itself to collecting evidence through randomised controlled trials just as it would for other therapies. Furthermore, doctors, patients, researchers and funders must all collaborate to allow the smooth implementation of precision medicine into clinical practice. Examples of such collaborations are the IGNITE and CSER2 consortia in the US, which are being funded by the National Human Genome Research Institute (NHGRI).
There will have to be considerable collaboration between stakeholders to allow the aims of precision medicine to be delivered. Even then, it is unlikely that the utopian vision of precision medicine that is so commonly touted will come to fruition; the gaps in our understanding and data processing capabilities place that future somewhat beyond our present reach. However, in small ways precision medicine is becoming one of the tools the clinician has at their disposal, and it is crucial that it is implemented with the aim of improving patient care rather than for the sole benefit of advancing innovation. And finally, as A Cecile JW Janssen writes, the end goal of precision medicine should be whatever the patient desires it to be.