Identification of Biomarkers Flashcards
What is the definition of biomarkers?
A defined characteristic that is measured as an indicator of normal biological processes, pathogenic process, or responses to an exposure or intervention, including therapeutic interventions
What are the different types of biomarkers organized by the source of information?
- Molecular characteristics
- Histological characteristics
- Radiographic characteristic
- Physiological characteristic
Does a biomarker always indicate a patient’s clinical presentation?
Not necessarily
ex. perfectly healthy patients with detected BCRA1 allele
What are some characteristics of molecular biomarkers?
They are molecules measured in biological samples (small molecules, proteins, DNA, and RNAs)
What are some characteristics of radiographic biomarkers?
A characteristic derived from medical images (ex. CT scan result)
What are some characteristics of histological biomarkers?
They reflect biochemical or molecular changes in cells, tissues, or fluids (ex. used for cancer staging and grading, increased differentiation = higher survival)
What are some characteristics of physiological biomarkers?
They are measurements of body processes (ex. blood sugar, blood pressure)
What are different levels of the cancer grading system?
GX: Grade cannot be assessed
G1: Well differentiated (low grade)
G2: Moderately differentiated (high grade)
G3: Poorly differentiated (high grade)
G4: Undifferentiated high grade (higher risk of mortality)
What are the six qualities of an ideal biomarker?
- Sensitive and specific (should not result in false positives or negatives)
- Stratify the risk of progression
- Cost effective (matters to publically-funded healthcare systems)
- Personalized management
- Quantifiable
- Correlate to clinical outcome (what is the impact of biomarker to health)
Compare and contrast genomics + transcriptomics vs. proteomics + metabolomics
Genomics + transcriptomics (closer to phenotype and is cheaply sequenced, so used more often)
Proteomics + transcriptomics (closer to genotype, but is more expensive)
What are the categories of biomarkers by what can be deduced from the results?
- Susceptibility/risk
- Diagnostic
- Monitoring
- Prognostic
- Predictive
- Pharmacodynamic/response
- Safety
What is the definition of susceptibility/risk biomarkers?
They indicate the potential of developing a disease or medical condition (the patient does not have the condition as of time of test)
ex. testing healthy patients for BCRA1/2 mutations
What is the definition of diagnostic biomarkers?
They are used to detect or confirm a disease of medical condition
ex. GFR is a proxy for kidney function
What is an example of a diagnostic biomarker test?
FoundationOne Liquid X
Analyzes over 300 genes including BRCA1/2, PIK3CA
What is the definition of monitoring biomarkers?
They are measured repeatedly to assess the status of a disease or medical condition
With disease progression (one may see increases in biomarker levels) or to monitor treatment response
What are some examples of a monitoring biomarker?
CA115 is a monitoring biomarker for ovarian cancer (increased levels of CA115 = progression of ovarian cancer)
PSA (prostate-specific antigen) is a monitoring biomarker for prostate cancer (high PSA level = prostate cancer)
What is the definition of prognostic biomarker?
It is used to identify the likelihood of health outcome (ex. disease recurrence or progression) in patients who have already diagnosed with the disease or medical condition (treatment has yet to be initiated)
What is an example of a prognostic biomarker?
ERBB2 (HER2) is a prognostic biomarker for endometrial carcinoma (does not measure treatment response)
Low expression = better prognosis
What is the definition of predictive biomarkers?
They are used to identify individuals who are more likely to respond towards a treatment than those without the biomarker
What is the benefit of predictive biomarkers?
We can select patients for a particular treatment and assessing the most likely response (helps reduce the use of unecessary therapies or doses)
What is an example of a predictive biomarker?
ERBB2 (HER2) is a predictive biomarker for breast cancer
10-15% of patients with breast cancer have HER2 overexpressed (now we will focus therapy on drugs that are known to be effective in HER2 positive breast cancer)
ex. Trastuzumab, pertuzumab, T-DM1, and lapatinib
Review slide 25 and its concepts (will come on exam)
What is the definition of pharmacodynamic/response biomarker?
They are measures of the effect of a drug on biological/pharmacological functions
Its levels change in response to the drug treatment (useful in determining the effective dose and dose schedule)
What are the pharmacodynamic assessments for cancer?
Invasive approaches:
- Serial tumour biopsies/analysis
- Surrogate tissue biopsies
- Neoadjuvant/window-of-opportunity trials
Noninvasive approaches:
- Circulating biomarkers (ctDNA, CTCs)
- Toxicity-based assessments
- Non-invasive imaging (ex. PET)
What is the definition of a safety biomarker?
They indicate the likelihood, presense or extent of toxicity
ex. urine albumin is a safety biomarker for nephrotoxicity
They can help identify patients who should avoid a particular therapy
What are pharmacogenomic biomarkers?
They demonstrate inter-individual genetic on the pharmacokinetics, pharmacodynamics, efficacy, and safety of drug treatments
ex. Genetic variants of P450s
What P450 enzyme has the most number of SNPs?
CYP 2D6
Which P450 enzyme is involved in the metabolism of the most number of drugs?
CYP 3A4
