Cancer Biomarkers

Cancer Biomarkers

1. INTRO

   • Biomarker definition
     • bioimarkers can be described as measurable and quantifiable biological indicators of normal physiological function, disease states, or of the body's response to therapeutics.
     • Biomarkers are present in bodily fluids, such as blood and blood fractions (plasma, serum etc), urine, saliva and tissues.
     • 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
     • The Biomarkers Definitions Working Group (2001) classified the different types of biomarker based on function
       • Biomarkers can be
         • Diagnostic
         • Prognostic
         • Predictive
         • Staging
         • Surrogate endpoints

2. Diagnostic Biomarkers

   • function:
     • diagnostic tool for identification of patients with a disease or abnormal condition
       • e.g. elevated blood glucose in individuals with diabetes mellitus
   • widely used in diagnosis of cancer
     • have the ability to determine the primary tumour in cases where it has metastasised

3. Prognostic Biomarkers

   • Prognosis refers to the natural course of the disease in the absence of treatment
     • takes place after an individual has been diagnosed with cancer
   • Clinical example
     • breast cancer
       • better prognosis in patients that are ER+/PR+/HER+
       • poor prognosis for cancers negative for these receptors
   • Some cancers more aggressive than others
     • biomarkers can help distinguish between rapidly growing and slowly growing cancers
       • patients can then receive different treatment
         • patients with slowly growing tumours may be spared aggressive treatments

4. Predictive Biomarkers

   • give an indication as to the
     • likely response to treatment
     • likelihood of developing a disease
     • likelihood of disease recurrence
   • clinical importance:
     • some cancers that affect the same part of the body may exhibit differences from person to person
       • can influence how they respond to treatment
   • EXAMPLE
     • Human Epidermal Growth Factor Receptor 2 gene (HER2)
       • 1/4 of breast cancer patients have a mutation in HER2 gene
         • causes overexpression of HER2
       • HER2+ breast cancers are likely to respond to Trastuzimab, which inhibits HER2 protein activity
         • HER2- patients will not respond to Trastuzimab and so are not given this therapy
       • HER2 overexpression causes breast cancers to rapidly grow and divide
         • aggressive cancer
       • HER2 us a prognostic AND predictive biomarker
     • OncotypeDX is used in early stage ER+ patients who will be treated with hormone therapy
       • evaluates a panel of 21 genes from a tumour biopsy sample
         • results in the form of a recurrence score indicating the likelhood of tumour recurring in the next 10 years

5. Staging Biomarkers

   • used as a tool to classify the extent or stage of the disease
   • Example
     • CA-125 elevation in ovarian cancer
     • PSA concentration in blood
       • reflects extent of tumour growth and metastasis in prostate cancer

6. Surrogate endpoints

   • clincal endpoint is a characteristic or variable that reflects how a patient feels, functions or survives
     • they are distinct measurements of disease characteristics observed in a study that reflect the effect of therapeutic intervention
   • A surrogate endpoint is a biomarker that is intended to substitute for a clinical endpoint
     • it is expected to predict clinical benefit based on epidaemiologic, therapeutic, pathophysiologic or other scientific evidence
   • EXAMPLE:
     • effect of drug therapy on cancer progression and survival
       • use of a validated surrogate endpoint would prevent patients having to undergo tumour biopsies and trials to see if a drug worked
       • Instead, a blood test could be performed to determine whetehr the biomarker has increased or decreased in response to the drug