With advances in genomics, drugs could be more effective than ever
One of the main justiﬁcations for human genetic research is the prospect of medicines tailored to a patient’s individual make-up – pharmacogenetics.
The idea is that a patient would be diagnosed with, say, heart disease and a doctor would do a quick test to ﬁnd out which drug would work best on them or which drug they shouldn’t take because of its likely side-effects. It’s an appealing vision, but how realistic is it?
Pharmacogenetics may well be the future, but it’s likely to be some time arriving.
There are some applications:
- Trastuzumab (Herceptin) is prescribed only for breast cancer patients with HER2 mutations.
- Imatinib is given to chronic myeloid leukaemia patients with a speciﬁc chromosome abnormality.
- The anti-HIV drug abacavir causes a rash in 5 per cent of patients with a particular gene variant. Patients can be screened before medication is given.
Among the most signiﬁcant factors in pharmacogenetics are the cytochrome P450 (CYP) enzymes, which metabolise drugs and are found mainly in the liver. Many different forms of CYP enzyme exist, and each form may have many variants. The way an enzyme metabolises a drug may therefore differ signiﬁcantly. Duplication of CYP2D6 has been linked to a poor response to antidepressants; other variations underlie limited response to painkillers such as codeine. One potential use is to screen people for CYP2C9 variations, which predict how well people respond to warfarin (a drug that’s used to prevent blood clotting but can also cause excessive bleeding).
Unfortunately, although its promise is great, the translation of pharmacogenetics into clinical practice is likely to be slow.
The identiﬁcation of a variant linked to a particular drug response is only the beginning. Many factors are likely to inﬂuence the body’s response to a drug, and clinical trials will be needed to conﬁrm that patients actually beneﬁt from targeted treatment – something that so far has rarely been done. Even then, the practicalities of changing healthcare delivery will have to be tackled.
Industry will also have to respond to the pharmacogenetic challenge. Drugs being targeted to a subset of the population could mean that pharmaceutical companies are no longer able to produce ‘blockbuster’ drugs (drugs that are widely used and generate vast profits). Ruling out non-responders could reduce market size by 30–40 per cent.
On the other hand, a better understanding of disease will suggest new drug targets. Clinical trials could be streamlined – only responders would be included. Pharmacogenetics could identify groups at risk of an adverse reaction. This might mean a new life for drugs that work but are currently too risky to use.