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PHAR 211 > Identification of Biomarkers > Flashcards

Identification of Biomarkers Flashcards

1
Q

What is the definition of biomarkers?

A

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

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2
Q

What are the different types of biomarkers organized by the source of information?

A
  • Molecular characteristics
  • Histological characteristics
  • Radiographic characteristic
  • Physiological characteristic
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3
Q

Does a biomarker always indicate a patient’s clinical presentation?

A

Not necessarily

ex. perfectly healthy patients with detected BCRA1 allele

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4
Q

What are some characteristics of molecular biomarkers?

A

They are molecules measured in biological samples (small molecules, proteins, DNA, and RNAs)

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5
Q

What are some characteristics of radiographic biomarkers?

A

A characteristic derived from medical images (ex. CT scan result)

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6
Q

What are some characteristics of histological biomarkers?

A

They reflect biochemical or molecular changes in cells, tissues, or fluids (ex. used for cancer staging and grading, increased differentiation = higher survival)

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7
Q

What are some characteristics of physiological biomarkers?

A

They are measurements of body processes (ex. blood sugar, blood pressure)

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8
Q

What are different levels of the cancer grading system?

A

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)

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9
Q

What are the six qualities of an ideal biomarker?

A
  1. Sensitive and specific (should not result in false positives or negatives)
  2. Stratify the risk of progression
  3. Cost effective (matters to publically-funded healthcare systems)
  4. Personalized management
  5. Quantifiable
  6. Correlate to clinical outcome (what is the impact of biomarker to health)
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10
Q

Compare and contrast genomics + transcriptomics vs. proteomics + metabolomics

A

Genomics + transcriptomics (closer to phenotype and is cheaply sequenced, so used more often)

Proteomics + transcriptomics (closer to genotype, but is more expensive)

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11
Q

What are the categories of biomarkers by what can be deduced from the results?

A
  • Susceptibility/risk
  • Diagnostic
  • Monitoring
  • Prognostic
  • Predictive
  • Pharmacodynamic/response
  • Safety
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12
Q

What is the definition of susceptibility/risk biomarkers?

A

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

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13
Q

What is the definition of diagnostic biomarkers?

A

They are used to detect or confirm a disease of medical condition

ex. GFR is a proxy for kidney function

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14
Q

What is an example of a diagnostic biomarker test?

A

FoundationOne Liquid X

Analyzes over 300 genes including BRCA1/2, PIK3CA

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15
Q

What is the definition of monitoring biomarkers?

A

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

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16
Q

What are some examples of a monitoring biomarker?

A

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)

17
Q

What is the definition of prognostic biomarker?

A

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)

18
Q

What is an example of a prognostic biomarker?

A

ERBB2 (HER2) is a prognostic biomarker for endometrial carcinoma (does not measure treatment response)

Low expression = better prognosis

19
Q

What is the definition of predictive biomarkers?

A

They are used to identify individuals who are more likely to respond towards a treatment than those without the biomarker

20
Q

What is the benefit of predictive biomarkers?

A

We can select patients for a particular treatment and assessing the most likely response (helps reduce the use of unecessary therapies or doses)

21
Q

What is an example of a predictive biomarker?

A

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

22
Q

Review slide 25 and its concepts (will come on exam)

A
23
Q

What is the definition of pharmacodynamic/response biomarker?

A

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)

24
Q

What are the pharmacodynamic assessments for cancer?

A

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)

25
Q

What is the definition of a safety biomarker?

A

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

26
Q

What are pharmacogenomic biomarkers?

A

They demonstrate inter-individual genetic on the pharmacokinetics, pharmacodynamics, efficacy, and safety of drug treatments

ex. Genetic variants of P450s

27
Q

What P450 enzyme has the most number of SNPs?

A

CYP 2D6

28
Q

Which P450 enzyme is involved in the metabolism of the most number of drugs?

A

CYP 3A4

29
Q
A

PHAR 211 (18 decks)

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