Biomarkers Flashcards
Define biomarker.
characteristic that is objectively measured & evaluated as an indicator of normal biological/pathogenic processes or response to a therapeutic invention
Where can you measure biomarkers?
Serum
urine
tissue
saliva
blood cells
any accessible body fluid
What are technologies used to measure biomarkers?
Ion selective electrodes
Immunoassay
Immunohistochemistry
spectrophotometry
PCR/RT-PCR
DNA sequencing
Where does biomarker testing occur?
Hospital laboratories
commercial laboratories
point-of-care
over the counter
pharmaceutical industry
When are biomarkers used?
Disease detection & management
Drug discovery and evaluation
What are 6 uses for biomarkers?
Risk identification
screening
aiding diagnosis
assessing prognosis
therapy prediction
monitoring
What are 4 predisposing genes for disease?
BRCA1 - breast, prostrate & ovarian
BRCA2 - breast, prostrate & ovarian
HFE - haemochromatosis
CF gene - cystic fibrosis
What are 3 screening tests?
mammography
FOB (Crc)
PAP/HPV
What is PSA screening test used for?
For prostrate cancer
What are benefits of PSA?
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
What are 2 arguments against PSA?
Overdiagnosis
overtreatment
What are 5 diagnostic biomarkers?
Glucose - diabetes
Troponin - MI
urea & creatinine - renal disease
Albumin - liver
t4/TSH - thyroid disease
What are prognostic markers used to assess?
Disease aggressiveness & patient outcome -> avoids under/over treatment
What is the challenge with lymph-node negative BC?
Differentiate the majority who are cured from surgery from the minority that need chemo
What test was used to identify if chemo wasnt needed?
uPA & PAI-1
Why do we need therapy predictive markers?
Only a proportion of Pts with a specific disease respond to a specific therapy
many therapies are toxic
some therapies are v expensive
What are 6 predictive biomarkers used to target in cancers?
HER2 - breast
EGFR - lung
KRAS/NRAS - CRC
BRAF - melanoma
ALK - lung
ER/PR - breast
What is a benefit of Herceptin in HER2+ BC?
10-15% of Pts with metastatic BC now have long-term outcome & may be cured
How amplified in the HER2 gene in BC?
15-20%
What does increased expression of HER2 dfrive?
BC formation & metastasis
What do Mabs against HER2 block?
HER2 signalling -> blocking HER2-driven proliferation
How is monitoring used for serial levels of markers?
Serial levels of markers can detect recurrent or metastatic disease prior to clinical or radiological criteria
Determines if Pt is responding to treatment
What are future developments for tumour markers?
Mutated genes (ctDNA)
Methylated genes
circulating tumour cells
gene expression microarray
proteomics
miRNAs
What are 5 major causes of attrition in drug development?
Lack of efficacy
toxicity
commercial factors
costs
bioavailability
