Progress in mainstreaming genomics into clinical practice

Corinna Alberg

30 September 2015

New policy update on genomics and oncology

The American Society of Clinical Oncology (ASCO) has just published a policy statement update on genetic and genomic testing for cancer susceptibility. This was commissioned by the prevention and ethics committee of the Society and aims ‘to reflect the impact of advances in this area on oncology practice’ and to highlight the opportunities for cancer susceptibility testing.  While there have been concerns that the promise of genomics has been hyped, it is clear that genomics is impacting on clinical practice for the treatment of those with cancer. 

Targeted therapies

Testing for germline mutations has been available in clinical practice for almost 20 years for heritable cancer susceptibility such as BRCA 1 and 2 mutations in familial breast and ovarian cancer syndrome. In contrast, somatic mutation profiling has entered clinical practice more recently. The advent of much cheaper and higher throughput next generation DNA sequencing has heralded the introduction of somatic mutation profiling. This method of profiling tumour cells’ DNA can identify mutations that are driving cancer in individual patients (so-called driver mutations);  in some cases therapeutics exist that target those same mutations, and choosing such a targeted therapy maximises treatment response. 

The number of targeted drugs or therapies has risen sharply in recent years from around 15 in 2008 to over 60 today that have been approved by the FDA. The most ‘druggable’ targets are for lung and haematological malignancies, which, although a small subset of all cancer types, account for a large proportion of cancer patients.  Lung cancer is the most prevalent form of cancer worldwide, with 1.8 million new cases diagnosed in 2012 including 36% of all newly diagnosed cancer cases occurring in China. According to Professor Dennis Lo of the Chinese University of Hong Kong, 40% of Chinese lung cancer patients have a mutation in the EGFR gene, which is a therapeutic target. While not all patients will have mutations that will respond to existing targeted therapies, the high prevalence of lung cancer globally highlights the impact that genomics could be making. This will only increase as the number of targeted therapies increases. 

Liquid biopsies to monitor cancer

Another development that will contribute to the impact of genomics on clinical practice in oncology is the use of liquid biopsies – blood tests to evaluate tumour status, a method first reported in 2007.Liquid biopsies analyse the small fragments of DNA shed by tumour cells into the blood. In contrast, traditional tissue biopsies usually require invasive procedures and are difficult to obtain for inaccessible and fragile organs like the lungs. So liquid biopsies can help identify cancer presence or recurrence without the need for a tissue biopsy. Moreover, the diversity of mutations within a single tumour means that a standard tissue biopsy may not be representative of the whole tumour and analysis may fail to identify the crucial driver mutations - unlike a liquid biopsy, which produces a more comprehensive view of tumour diversity. Liquid biopsies have the potential to allow clinicians to monitor whether current treatments are working, or whether there are signs of recurrence due to the tumour developing resistance and other mutations becoming the new driver mutation. Whilst this approach is at present still mainly employed in the research arena, liquid biopsies are seen as a future ‘game changer’ for personalised cancer care. 

Genomics in other specialties

For many areas of medicine, genomics can have a large impact on a subset of patients. A recent paper in the Lancet highlighted the impact of genetic testing on the outcomes of patients with neonatal diabetes; using genetic testing as the initial investigation (rather than later as per usual practice, to confirm a diagnosis) had a great benefit.   Genetic testing can distinguish between isolated permanent diabetes, transient neonatal diabetes and patients in whom the diabetes is part of the presenting features of a more complex syndrome. For this latter group of patients, early genetic testing can enable the rapid detection and management of additional clinical features of the syndrome. For example, in Wolcott-Rallison syndrome liver failure is life-threatening, but can be managed more effectively if liver complications are detected as part of syndrome diagnosis. Genetic testing can also distinguish between those for whom the diabetes resolves, those who will respond to insulin or sulfonylurea which can be taken orally, and those who will require pancreatic enzyme replacement in addition to insulin treatment. 

Early genetic testing also offers potential clinical utility in many other specialties such as ophthalmology, enabling some patients to be identified as suitable candidates for gene therapy. In cardiology, understanding which gene is responsible for an arrhythmia may suggest different interventions, and can also help identify other family members who may be at risk from sudden cardiac death. Similarly, genetic screening for familial hypercholesterolemia can identify asymptomatic patients and allows effective treatment with statins to prevent sudden cardiac death.  

Mainstreaming genomics in clinical practice

For all areas of clinical practice, the education of health professionals is key to patients being able to access high quality genomic services. The ASCO policy update highlights the need for professionals to develop core competences in genetics - a level of knowledge that typically exceeds that received during training.  

In the UK, the PHG Foundation is working in collaboration with the Royal College of Physicians (RCP) to improve knowledge of genomics in the range of specialties that comes under the RCP umbrella.  The aim is to raise awareness of the impact that genomics is already making in certain specialties, and in certain aspects of clinical care such as pharmacogenomics. Introductory resources are being developed by clinical champions within each specialty.