What is pharmacogenomics?
The study of how the whole genome can influence a drug response.
What is pharmacogenetics?
The study of genetic causes of individual variations in drug responses.
- it involves looking at how specific genes will influence the response to a drug.
What is a genome?
The complete genetic information of an organism.
What is a gene?
A specific sequence of DNA that codes for a functional molecule (ie a protein).
Briefly, why do we carry out genomics testing? 🧬
- ✅ for diagnostic purposes (ie cancer, infectious disease, rare and inherited conditions).
- ✅ prediction of risk (ie for developing a condition)
- ✅ identification of carriers of certain genetic traits for disease - will inform reproductive choices.
- ✅ individualise drug selection ie if we know a patient has certain genomic traits we can match treatment to that (ie HER2+ and Herceptin)
- ✅ individualise dosing regimen ie if we know a patient is fast or slow metabolisers, or able to activate products, or liable to ADRs we can then adjust their dosing regimen accordingly. (Ie fast metaboliser of codeine - reduce dosing interval to avoid accumulation and tox).
Give 3 examples of diseases or conditions which we can use to test for treatment selection?
- ✅ cystic fibrosis
- ✅ familial hypercholesterolaemia
- ✅ lung cancer
Describe how Pharmacogenomics plays a role in treatment selection for cystic fibrosis?
CF is a respiratory condition where there is a variant in both copies of the cystic fibrosis transmembrane conductance regulator (CFTR) gene.
- the delta F508 variant is more common and based on these variants we can develope targeted treatments that can be used only in patients with those mutations.
Eg medications Katyro.
Describe how Pharmacogenomics plays a role in treatment selection for Familial Hypercholesterolaemia.
There are lots of variants involving siRNA in the LDL cholesterol receptor and other proteins which we can treat with targeted therapies (ie PCSK9 - MCAB) or siRNA
Describe how Pharmacogenomics plays a role in treatment selection Lung Cancer.
25% KRAS genes in lung are altered :
- lots EGFR variants which depending on what they are we can use 1st, 2nd or 3rd generation TKI’s to treat. Depending on your genomics we may use a particular TKI over the other.
- ALK fusions - treated with alectinib, brigantinib , certinib, crizotinib etc.
- lots of other genetic mutations invoved in lung cancer.
Which type of lung cancer can we use Pharmacogenomics based therapies to treat?
Non - small cell cancer.
