Cancer Biomarkers

INTRO
1. Biomarker definition
  1. bioimarkers can be described as measurable and quantifiable biological indicators of normal physiological function, disease states, or of the body's response to therapeutics.
  2. Biomarkers are present in bodily fluids, such as blood and blood fractions (plasma, serum etc), urine, saliva and tissues.
  3. Biomarkers, while often considered to only be proteins, can also take the form of a specific measurement such as an ECG or imaging test (E.g. MRI or CT scan) or can be a physical assessment or verbal test
  4. The Biomarkers Definitions Working Group (2001) classified the different types of biomarker based on function
    1. Biomarkers can be
      1. Diagnostic
      2. Prognostic
      3. Predictive
      4. Staging
      5. Surrogate endpoints
Diagnostic Biomarkers
1. function:
  1. diagnostic tool for identification of patients with a disease or abnormal condition
    1. e.g. elevated blood glucose in individuals with diabetes mellitus
2. widely used in diagnosis of cancer
  1. have the ability to determine the primary tumour in cases where it has metastasised
Prognostic Biomarkers
1. Prognosis refers to the natural course of the disease in the absence of treatment
  1. takes place after an individual has been diagnosed with cancer
2. Clinical example
  1. breast cancer
    1. better prognosis in patients that are ER+/PR+/HER+
    2. poor prognosis for cancers negative for these receptors
3. Some cancers more aggressive than others
  1. biomarkers can help distinguish between rapidly growing and slowly growing cancers
    1. patients can then receive different treatment
      1. patients with slowly growing tumours may be spared aggressive treatments
Predictive Biomarkers
1. give an indication as to the
  1. likely response to treatment
  2. likelihood of developing a disease
  3. likelihood of disease recurrence
2. clinical importance:
  1. some cancers that affect the same part of the body may exhibit differences from person to person
    1. can influence how they respond to treatment
3. EXAMPLE
  1. Human Epidermal Growth Factor Receptor 2 gene (HER2)
    1. 1/4 of breast cancer patients have a mutation in HER2 gene
      1. causes overexpression of HER2
    2. HER2+ breast cancers are likely to respond to Trastuzimab, which inhibits HER2 protein activity
      1. HER2- patients will not respond to Trastuzimab and so are not given this therapy
    3. HER2 overexpression causes breast cancers to rapidly grow and divide
      1. aggressive cancer
    4. HER2 us a prognostic AND predictive biomarker
  2. OncotypeDX is used in early stage ER+ patients who will be treated with hormone therapy
    1. evaluates a panel of 21 genes from a tumour biopsy sample
      1. results in the form of a recurrence score indicating the likelhood of tumour recurring in the next 10 years
Staging Biomarkers
1. used as a tool to classify the extent or stage of the disease
2. Example
  1. CA-125 elevation in ovarian cancer
  2. PSA concentration in blood
    1. reflects extent of tumour growth and metastasis in prostate cancer
Surrogate endpoints
1. clincal endpoint is a characteristic or variable that reflects how a patient feels, functions or survives
  1. they are distinct measurements of disease characteristics observed in a study that reflect the effect of therapeutic intervention
2. A surrogate endpoint is a biomarker that is intended to substitute for a clinical endpoint
  1. it is expected to predict clinical benefit based on epidaemiologic, therapeutic, pathophysiologic or other scientific evidence
3. EXAMPLE:
  1. effect of drug therapy on cancer progression and survival
    1. use of a validated surrogate endpoint would prevent patients having to undergo tumour biopsies and trials to see if a drug worked
    2. Instead, a blood test could be performed to determine whetehr the biomarker has increased or decreased in response to the drug

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Cancer Biomarkers

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