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SSC- Biology of Cancer > Cancer Biomarkers > Flashcards

Cancer Biomarkers Flashcards

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1
Q

Define the term cancer biomarker

A

A substance or process that is indicative of the presence of cancer in the body

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2
Q

What are the uses of cancer biomarkers in practice?

A
  • Risk/screening
  • Prognosis
  • Prediction (response to treatment)
  • Recurrence/monitoring
  • Diagnosis
  • Pharmacodynamics
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3
Q

What are the categories of biomolecules that can be cancer biomarkers

A
  • Genetic
  • Epigenetic
  • Proteomic
  • Glycomic
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4
Q

What are the genetic cancer biomarkers?

A
  • DNA mutations
  • mRNA expression
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5
Q

What are the epigenetic cancer biomarkers?

A
  • DNA methylation
  • Histone methylation
  • miRNA gene silencing
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6
Q

What are the proteomic cancer biomarkers?

A
  • Protein levels
  • PTM
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7
Q

What are the glycomic cancer biomarkers?

A

Glucose metabolism

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8
Q

What sources can be tested for cancer biomarkers?

A
  • Blood
  • Fine-needle aspirates
  • Fresh tissue
  • Frozen tissue
  • FFPE
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9
Q

What are the features of an ideal cancer biomarker?

A
  • Specific
  • Sensitive
  • Predictive
  • Robust
  • Reflect kinetics
  • Minimally invasive
  • Clinical importance
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10
Q

What should a cancer biomarker be specific to?

A
  • Disease type
  • Disease stage
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11
Q

How sensitive should the ideal biomarker be?

A

Ideally should detect a single molecule

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12
Q

What should the ideal biomarker be predictive of?

A
  • Stratification
  • Treatment response
  • Recurrence
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13
Q

What factors are considered when deciding if a biomarker is robust?

A
  • Fast
  • Simple
  • Cheap
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14
Q

What features must biomarkers have if they are to be used for cancer screening?

A
  • Must be highly specific
  • Must be able to clearly reflect different stages of the disease
  • Must be easily detected without complicated medical procedures
  • Method of screening must be cost effective
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15
Q

Why must cancer biomarkers used for screening be highly specific?

A

To minimise false positives and negatives

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16
Q

What markers are good targets for application of early screening?

A

Markers released to the serum and urine

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17
Q

What is prostate specific antigen produced by?

A

Epithelial cells of the prostate

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18
Q

What levels of PSA are considered suspicious?

A

4-10ng/ml

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19
Q

What is required when PSA is 4-10ng/ml?

A

Biopsy

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20
Q

How is PSA used in risk stratification?

A

Used to stratify patients into low, intermediate, or high risk for having/developing metastatic disease, or dying of prostate cancer. It is used in conjunction with two other parameters - grade (Gleason grading) and stage (imaging)

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21
Q

Where is HPV detected?

A

Almost all cases of cervical cancer

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22
Q

How are cervical cells collected?

A

Using a Pap smear

23
Q

Who is screened for cervical cancer in the UK?

A

Women aged 25 to 64 years - 25-49 years screened every 3 years, 50-64 screened every 5 years

24
Q

How is cancer traditionally diagnosed?

A

Using tissue biopsy, on which immunohistochemistry and pathological evaluation are performed

25
Q

What is the problem with using biopsy to diagnose cancer?

A
  • Highly invasive
  • Expensive
26
Q

Define diagnostic biomarkers

A

Substances that are produced by cancer, or by other cells of the body, in response to cancer or certain benign conditions.

27
Q

Are tumour markers made by normal cells?

A

Most are, however are produced much higher levels in cancerous conditions

28
Q

Give 6 examples of diagnostic biomarkers

A
  • Alpha-fetoprotein in liver cancer
  • Cancer antigen 125 in ovarian cancer
  • CA15-3 in metastatic breast cancer
  • Carbohydrate antigen 19-9 in colorectal cancer
  • Carcinoembryonic antigen in pancreatic cancer
  • Prostate specific antigen in prostate cancer
29
Q

Give an example of a genetic diagnostic biomaker

A

BCR-ABL in CML (chronic myelogenous leukaemia)

30
Q

What % of patients with CML harbour a BCR-ABL translocation?

A

95%

31
Q

What drug targets BCL-ABL?

A

Imatinib

32
Q

What is a prognostic biomarker?

A

Indicates the likely course of the disease in an untreated individual

33
Q

What is the purpose of a predictive biomarker?

A

It identifies subpopulations of patients who are most likely to respond to a given therapy

34
Q

Why are predictive biomarkers clinically useful?

A
  • Predictive biomarker driven cancer therapy reduces the unnecessary treatment and adverse effects
  • Can quickly highlight acquired resistance to therapy
35
Q

Why is it important to reduce unnecessary treatment and adverse effects?

A
  • Safer - Certain chemotherapy regimens result in death rates in the range of 0.5-2.0%, and 30-40% patients experience grade 3 or 4 toxic effects
  • More clinical benefit
  • More cost effective
36
Q

Give three examples of predictive biomarkers

A
  • ERBB2 amplification
  • ECFR mutation
  • BRAF mutation
37
Q

What is ERBB2 mutation a marker for?

A

Highly aggressive breast cancers

38
Q

What is ERBB2 amplification targeed by?

A

Trastuzumab (Herceptin)

39
Q

What is mutated EGFR indicative of?

A

Response to erlotinib in NSCLC

40
Q

What is BRAF mutation indicative of?

A

Response to vemurafenib in metastatic melanoma

41
Q

What is cell free DNA derived from?

A
  • Apoptosis
  • Necrosis
  • Active secretion
42
Q

When are elevated levels of cell free DNA seen?

A

In tumour cell turnover

43
Q

What somatic alterations might occur in cell free DNA?

A
  • Point mutations
  • CNV
  • Structural rearrangements
  • Methylation of DNA
44
Q

Give an example of where cell free DNA can be used as a prognostic biomarker

A

ESR1 mutations in metastatic breast cancer

45
Q

What prognostic information can be determined from the presence of ESR1 cell free DNA?

A
  • Those with the mutation who had prior exposure to AIs are resistant to therapy
  • Reduced progression free survival in ES1 mutation positive patients
46
Q

How do circulating tumour cells (CTCs) get into the bloodstream?

A

They are shed

47
Q

What is the clinical use of CTCs?

A
  • Can be prognostic and predictive
  • Extremely useful monitoring tool
48
Q

What is the problem with circulating CTCs as a clinical tool?

A
  • Difficult to isolate
  • Rare
49
Q

What tools can be used to analyse CTCs?

A
  • Immunostatin
  • FISH
  • Sequence
  • qRT-PCR
  • Expression analysis
  • Cell culture
50
Q

What can circulating miRNAs be used as?

A
  • Diagnostic biomarkers
  • Prognostic biomarkers
  • Predictive biomakers
51
Q

What are the applications of miRNAs as diagnostic biomarkers?

A
  • Monitor asymptomatic high-risk individuals
  • Identification of early-stage cancer
  • Discriminate between benign and malignant disease
52
Q

What are the applications of miRNAs as prognostic biomarkers?

A
  • Predict disease outcome
  • Predict progression-free and overall survival
  • Discriminate between benign and malignant disease
53
Q

What are the applications of miRNAs as predictive biomakers?

A
  • Monitor sensitivity to therapy and therapy response
  • Aid treatment decisions

SSC- Biology of Cancer (11 decks)

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