Biomarkers

Question 1

Define biomarker.

Answer 1

characteristic that is objectively measured & evaluated as an indicator of normal biological/pathogenic processes or response to a therapeutic invention

Question 2

Where can you measure biomarkers?

Answer 2

Serum
urine
tissue
saliva
blood cells
any accessible body fluid

Question 3

What are technologies used to measure biomarkers?

Answer 3

Ion selective electrodes
Immunoassay
Immunohistochemistry
spectrophotometry
PCR/RT-PCR
DNA sequencing

Question 4

Where does biomarker testing occur?

Answer 4

Hospital laboratories
commercial laboratories
point-of-care
over the counter
pharmaceutical industry

Question 5

When are biomarkers used?

Answer 5

Disease detection & management
Drug discovery and evaluation

Question 6

What are 6 uses for biomarkers?

Answer 6

Risk identification
screening
aiding diagnosis
assessing prognosis
therapy prediction
monitoring

Question 7

What are 4 predisposing genes for disease?

Answer 7

BRCA1 - breast, prostrate & ovarian
BRCA2 - breast, prostrate & ovarian
HFE - haemochromatosis
CF gene - cystic fibrosis

Question 8

What are 3 screening tests?

Answer 8

mammography
FOB (Crc)
PAP/HPV

Question 9

What is PSA screening test used for?

Answer 9

For prostrate cancer

Question 10

What are benefits of PSA?

Answer 10

Vast majority of cancers detected are organ defined
detect PCA 10 yrs before clinical evidence of disease
detected at lower stage & more differentiated
death rates for PCA have decreased

Question 11

What are 2 arguments against PSA?

Answer 11

Overdiagnosis
overtreatment

Question 12

What are 5 diagnostic biomarkers?

Answer 12

Glucose - diabetes
Troponin - MI
urea & creatinine - renal disease
Albumin - liver
t4/TSH - thyroid disease

Question 13

What are prognostic markers used to assess?

Answer 13

Disease aggressiveness & patient outcome -> avoids under/over treatment

Question 14

What is the challenge with lymph-node negative BC?

Answer 14

Differentiate the majority who are cured from surgery from the minority that need chemo

Question 15

What test was used to identify if chemo wasnt needed?

Answer 15

uPA & PAI-1

Question 16

Why do we need therapy predictive markers?

Answer 16

Only a proportion of Pts with a specific disease respond to a specific therapy
many therapies are toxic
some therapies are v expensive

Question 17

What are 6 predictive biomarkers used to target in cancers?

Answer 17

HER2 - breast
EGFR - lung
KRAS/NRAS - CRC
BRAF - melanoma
ALK - lung
ER/PR - breast

Question 18

What is a benefit of Herceptin in HER2+ BC?

Answer 18

10-15% of Pts with metastatic BC now have long-term outcome & may be cured

Question 19

How amplified in the HER2 gene in BC?

Answer 19

15-20%

Question 20

What does increased expression of HER2 dfrive?

Answer 20

BC formation & metastasis

Question 21

What do Mabs against HER2 block?

Answer 21

HER2 signalling -> blocking HER2-driven proliferation

Question 22

How is monitoring used for serial levels of markers?

Answer 22

Serial levels of markers can detect recurrent or metastatic disease prior to clinical or radiological criteria
Determines if Pt is responding to treatment

Question 23

What are future developments for tumour markers?

Answer 23

Mutated genes (ctDNA)
Methylated genes
circulating tumour cells
gene expression microarray
proteomics
miRNAs

Question 24

What are 5 major causes of attrition in drug development?

Answer 24

Lack of efficacy
toxicity
commercial factors
costs
bioavailability

Question 25

How is drug development being improved

Answer 25

Biomarkers predicting drug efficacy
biomarkers that predict toxicity