Personalised Medicines/Precision Medicine

Question 1

What is Personalised Medicine?

Answer 1

Personalised medicine is defined as health care that is individually tailored on the basis of a person’s genes, lifestyle and environment

Question 2

What are Pharmacokinetic Sources of Variability in Drug Response?

Answer 2

Age

Comorbidities (e.g. renal and hepatic function)

Protein binding and drug distribution

Drug-drug interactions

Genetic differences (pharmacogenetics)

Question 3

What are Pharmacodynamic Sources of Variability in Drug Response?

Answer 3

Age

Alterations in expression and/or structure of target (pharmacogenetics)

Question 4

What is a Genome?

Answer 4

Complete DNA within an organism

Question 5

What is DNA composed of?

Answer 5

o	Adenine (A)
o	Cytosine (C)
o	Guanine (G)
o	Thymine (T)

Question 6

A single cell contains how many DNA base pairs?

Answer 6

A single cell contains about 3 billion DNA base pairs, which is included in 23 pairs of chromosomes

Question 7

Compare Exons and Introns

Answer 7

‘Genes’ (exons) make up 2% of these DNA bases and each cell usually contains 2 copies of each gene

Remainder (introns) is involved in chromosomal structure, dynamics and evolution

Question 8

What are Pharmacogenomic differences?

Answer 8

Changes in DNA

Question 9

What is Gene expression?

Answer 9

Measure mRNA/ amount of mRNA cell is producing/amount of gene being transcribed

Question 10

What are Quantitate protein or functional studies?

Answer 10

Measure protein/how much protein a cell is producing

Question 11

What is Genotype?

Answer 11

DNA level

Question 12

What is Phenotype?

Answer 12

Protein level

Question 13

What are Factors affecting Phenotype?

Answer 13

Concurrent diseases

Environmental exposures

Ethnicity

Age

Diet

Concurrent drugs

Gender

Question 14

What is Genomic Variability?

Answer 14

Differences between and within individuals

The 2 copies of the genes (most of the time) within individuals are identical

Question 15

Genomic Variability: What is Homozygote?

Answer 15

2 copies of genes are identical

Question 16

Genomic Variability: What is Heterozygote?

Answer 16

2 copies are different

Question 17

What are the Types of Genomic Variability?

Answer 17

Somatic (acquired) mutations

Germline (inherited) mutations

Question 18

What can Biomarkers be used to assess?

Answer 18

Can be used to assess the likely outcome or response to a treatment based on whether or not the patient has the biomarker

Question 19

What do Prognostic Biomarkers show in a graph?

Answer 19

With these biomarkers, the efficacy of all treatments is improved in patients carrying the biomarker, and vice versa as the biomarker can reduce efficacy too. In other words, if the patient is negative for the biomarker, they will get a bad response to any drug, but if they are positive, they will get a good response from any drug

Question 20

What do Predictive Biomarkers show in a graph?

Answer 20

These types of biomarkers are specific for a particular drug or treatment. The efficacy of that particular treatment is improved for carriers of the biomarker, but not for any other treatment

Question 21

What do Prognostic/Predictive Biomarkers show in a graph?

Answer 21

It is possible for a biomarker to be both predictive and prognostic in nature. This means that having this biomarker will mean you will get an increased response to all treatments (prognostic component), but you will get a better response to one treatment than all the others (predictive component)

Question 22

What is Germline DNA Variability?

Answer 22

Variability within own DNA that we’re born with and will live with

Question 23

What are the Types of Types of Pharmacogenomic Variability?

Answer 23

Single Nucleotide Polymorphism (SNP) or Single Base Pair Substitution Variability

Insertions, deletions and copy number variants (CNVs)

Question 24

Types of Pharmacogenomic Variability: What are Single Nucleotide Polymorphism (SNP) or Single Base Pair Substitution Variability?

Answer 24

E.g. ‘normal’ base pair in that position (e.g. 1000) is an Adenine, but in some people it’s a Thymine

Question 25

Types of Pharmacogenomic Variability: What are Insertions, deletions and copy number variants (CNVs)?

Answer 25

Bits of DNA inserted/transcribed

Deletion of DNA

Multiple copy of gene for particular protein

Question 26

Pharmacogenomic Variability: Variability can be on what?

Answer 26

Drug targets (pharmacodynamics markers)

Drug metabolising enzymes/transporters (pharmacokinetic markers)

Question 27

Types of Pharmacogenomic Variability: What are the types of Single Nucleotide Polymorphism (SNP) or Single Base Pair Substitution Variability?

Answer 27

Coding (non-synonymous) SNP [exon]: May result in a change in the amino acid sequence of the encoded protein

Non-Coding (Synonymous) SNP [intron]: Will not change protein sequence