Proliferation Biomarkers in Drug Discovery and Development, The Immunoassay of Thymidine Kinase 1

C.E. Credits: P.A.C.E. CE Florida CE


Proliferation biomarkers are proteins that are up-regulated in growing cells. Immunological staining of tumor tissue can provide an indication of the aggressivity of the tumor and provide information as to the likely therapeutic response. Most such biomarkers can only be measured immunohistologically requiring biopsy and making repeat sampling difficult. Thymidine Kinase 1 (TK1) is up-regulated in cells synthesising DNA and many studies have shown it to be found in increased concentrations in tumor tissue. However, uniquely TK1 is also measurable in body fluids making it a convenient biomarker for following cell proliferation. However, previous assays based on enzymatic activity have under-estimated TK1, particularly in samples from subjects with solid tumors, such as prostate and breast. Immunoassays using antibodies specific for the TK210 antigen increase the clinical sensitivity of TK1 and make the assay more robust. This presentation will demonstrate the value of TK1 immunoassays in the study of anti-tumor therapies in in-vitro, xenograft and pre-clinical studies. Examples will be taken from several tumor types, particularly recent data from studies on prostate cancer.

Learning Objectives:

1. Review how proliferation biomarkers can add value to studies with other tumor biomarkers.

2. Summarize Thymidine Kinase 1 as a mechanistic biomarker.

3. Review the use of Thymidine Kinase 1 immunoassay as a valuable translational biomarker applicable from drug discovery through to clinical trials.

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