Biomarkers in cancer

Biomarkers in cancer

• 1.
  Biomarkers in cancer “Acharacteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathological processes, or responses (pharmacologic or otherwise) to a therapeutic intervention”. Types of biomarkers Screening biomarkers A screening biomarker is a marker which identifies disease at an early stage  Cytological screening for cervical cancer  Mammography for breast cancer What might the problem be if there was population screening for bladder cancer? Too many false positives leading to expensive followup What group might screening for bladder cancer be beneficial for? At risk groups Risk / predisposition markers A risk/predisposition marker is a marker which identifies individuals at increased risk of developing cancer  BRCA1/2  APC  MLH1  Measures of carcinogen exposure – DNA adducts  Microsatellite instability Colorectal HNPCC
• 2.
  A risk/predisposition markerfor TCCB Retinoblastoma Mutant p53 People with polymorphisms in N-acetyltransferase – 2 and glutathione – S transferase genes who are exposed to carcinogens are at increased of bladder risk. This is because the gene products are involved in detoxification of bladder carcinogens. Diagnostic markers A diagnostic biomarker defines the type of cancer a patient has  Standard imaging  Pathology  PSA (PSA is a screening, diagnostic and surrogate biomarker)  CEA  CA-125 used in ovarian cancer  Calcitonin Thyroid cancer Why do we need a diagnostic biomarker for bladder cancer? Haematuria is non specific. Cytoscopy is very expensive. Diagnostic biomarkers currently being considered/assessed in TCCB: Urine based  Cytology  NMP22  BTA Stat/ BTA TRAK basement membrane protein antigen released into urine  FDP/ Accu – Dx  HA-HAase detects hyaluronidase which is a component of the extracellular matrix
• 3.
   BLC A-4nuclear matrix protein  Survivin  UBC cytokeratins 8 & 18  CYFRA 21-1  Urinary cytokeratin 19 Cell based: Immunocyt CEA Cytokeratin 20 Telomerase Quanticyte nuclear karyometry FISH Micro satellite DNA Prognostic biomarkers A prognostic biomarker indicates the likely course of the disease Why is there a need for prognostic biomarkers for patients with confirmed TCCB? Heterogeneity of response/prognosis in patients in the same pathological classification Prognostic biomarkers in all cancers: HER2 the growth factor receptor is a negative prognostic biomarker in breast cancer. However HER2 is a positive predictive biomarker of response to Herceptin – trastuzumab ie only patients with the HER2 amplification should be given Herceptin.
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  Prognostic biomarkers inTCCB:  MMP-9  Loss of E-cadherin  Mutant p53  Bcl-2  IL-8  VEGF Predictive biomarkers A predictive biomarker identifies subpopulations of patients who are most likely to respond to a given therapy  Breast cancer patients with oestrogen receptor positive tumours are more likely to respond to antiendocrine therapies  Only patients with HER2 amplification should be given trastuzumab (Herceptin) therapy. HER2 is a growth factor receptor.  Oncotype DX used in breast cancer as a predictor for response to adjuvant therapy with tamoxifen  Mutant EGFR used in colon and non small cell lung cancer as a predictor for EGFR inhibitors Pharmacological biomarkers Pharmacological markers measure the effects of a drug treatment on a specific target e.g., inhibition of enzymes, receptor blockade, induction of apoptosis (cell death), inhibition of cell proliferation, inhibition of angiogenesis. Pharmacological markers are used to demonstrate proof of mechanism and proof of concept at tolerated doses.
• 5.
  Surrogate response markers Surrogateresponse markers are biomarkers that can be used in place of clinically meaningful endpoints.  PSA  CEA  CA-125