Genomics in practice

Pharmacogenomics is the study of how an individual’s genetic makeup affects their response to medication and involves the use of genetic and genomic information to tailor treatment. The goal is to maximise efficacy and minimise toxicity where possible. In clinical practice, pharmacogenomics is used where the evidence base is robust enough to justify deviating from the standard treatment or dose, for example where a patient has a genetic variant that would mean they may not respond as intended to that treatment (see the case study, above, for an example). You can learn more in this GeNotes article: Introduction to pharmacogenomics.

The body–drug relationship

Genetic variation influences both what the body does to the drug (known as pharmacokinetics) and what the drug does to the body (known as pharmacodynamics). Consequently, certain genetic variants have come to be associated with the risk of adverse drug reactions or inefficacy.

Examples in clinical practice

• There are a large number of well-established drugs affected by pharmacogenomic variation in clinical practice today, although the NHS does not currently offer routine testing for all of them. Examples of these drugs include abacavir, carbamazepine and mavacamten.
• In 2020, the NHS rolled out the core pharmacogenomic test for DPYD, which tests 40,000 people annually when initiating fluoropyrimidine systemic anticancer treatment.
• In 2024, NICE released evidence-based recommendations on CYP2C19 genotype testing to guide clopidogrel use after ischaemic stroke or transient ischaemic attack. NICE is working with NHS England, who will initially deliver a pilot until mid-2025 to produce an implementation guide for providers and information to support future commissioning decisions.
• The feasibility of delivering a diagnostic service for pharmacogenetics within the NHS is being explored through the pharmacogenetics roll out – gauging response to service (PROGRESS) project.
• Internationally, the landmark pre-emptive pharmacogenomic testing for preventing adverse drug reactions (PREPARE) study investigated the utility of a pre-emptive pharmacogenomic panel and published its results in 2023.

You can read more about pharmacogenomics in GeNotes, or get a definition from our glossary entry.

As we learn more about the genomic basis for different diseases, we can create more treatments that are directly targeted to what causes them. We often refer to these types of treatments as ‘precision medicines’, which aim to provide the most beneficial result for the individual with the minimum side effects. Due to the specificity of these medicines, they may be less effective if the molecular causes of disease that they have been designed to target are absent.

In the NHS, patients suspected of carrying a genomic variant that could be ‘targeted’ by a medicine often need to have a genomic test first, to ‘unlock’ that treatment. This will usually be described in the drug’s licence or commissioning criteria.

Examples in clinical practice

• In cystic fibrosis, CFTR gene variants can produce malfunctioning protein. Treatments improve the production, processing or function of the CFTR protein to reduce symptoms.
• In familial hypercholesterolaemia, where an overactive PCSK9 variant leads to reduced sensitivity of the body to detect and respond to circulating cholesterol, the use of alirocumab and evolocumab inhibits the PCSK9 protein to allow patients to better control their LDL cholesterol levels.
• In cancer, including trastuzumab/pertuzumab for HER2-expressing breast cancer, and osimertinib for EGFR-mutated non-small cell lung cancer to target proteins not expressed in healthy cells.

A better understanding of genomic variation, biological pathways and mechanisms of disease can allow us to find new uses for existing medicines. This is important because developing new treatments can be a long and costly process, with no guarantee of success.

Use in rare and complex conditions

Although rare diseases are, as the name suggests, rare – they are collectively common, affecting 1-in-17 people in the UK. Identifying the molecular biology of a specific condition can help researchers and clinicians to match them to existing drugs that are known to be safe and effective within their licence. Data collected from studies (such as the deciphering developmental disorders (DDD) study introduced in this webinar) can be pivotal in helping to make these connections.

Conditions such as breast cancer, diabetes and Alzheimer’s disease are also difficult to treat because of the complex interplay of genes involved in their pathophysiology. Existing drugs can help us target points in those pathways that can have beneficial up- or downstream effects in the wider complex disease.

Examples in clinical practice

• The use of aspirin for the prevention of colorectal cancer in people with Lynch syndrome. This treatment was off-label in January 2020 but NICE now recommends its use.

Up to date information around genomic testing, diagnosis, management and treatment of health conditions can be found on GeNotes.

Genomic characteristics of tumours and infectious organisms (for example, bacteria and viruses) can help us to predict resistance to standard treatments and find alternative options.

Examples in clinical practice

• In oncology, tumour cells may mutate and become resistant to a previously effective targeted treatment. Serial sampling of cancer cells and further genomic testing can help reveal the molecular causes of treatment resistance and guide changes in therapy.
• Pulmonary tuberculosis is caused by a bacteria that often carries many antimicrobial drug resistance genes. Genomic sequencing allows us to rapidly analyse a microbe’s genome to see which resistance genes it carries, and therefore optimise treatment more quickly. You can read more around antimicrobial resistance in this resource from the Royal Pharmaceutical Society.

Gene therapies are treatments that modify the genome to treat or prevent a particular genetic condition or disease. They use cutting-edge technology to deliver tailor-made genetic material into a person’s cells, usually with long-lasting or permanent effects.

Examples in clinical practice

• Onasemnogene abeparvovec (branded as Zolgensma) provides a new, functioning copy of the SMN1 gene to patients with spinal muscular atrophy (SMA). The therapy is a viral vector that specifically ‘infiltrates’ and targets the motor neurons that would normally produce the protein (which those with the condition are deficient in). More information about SMA therapies can be found in this 60-minute webinar with Dr Louise Hartley.