Advanced breast cancer care today
Thanks to progress with new therapies, the short-term outlook has improved. For patients with hormone receptor positive disease, there are often lengthy responses to therapy. The number of therapeutic options has increased. With these changes, quality of life, confident decision-making, switching treatments at the right time, and managing costs become more important. Monitoring of metastatic breast cancer today is a collection of tests, including imaging, tumor markers, routine lab tests, symptoms, and a physical exam.
“Monitoring treatment response in MBC remains a clinical challenge and current guidelines suggest a combination of imaging, clinical assessment and in addition application of serum tumor markers if initially elevated. Imaging is golden standard for tumor response evaluations in patients with measurable disease. However, studies report that 10–40% of MBC patients have non-measurable disease. There is a clinical need for better tools to improve prognostication and therapy monitoring in MBC.”
Larsson et al, “Serial evaluation of serum thymidine kinase activity is prognostic in women with newly diagnosed metastatic breast cancer” Nature Scientific Reports, March 2020, 10:4484
The role of thymidine kinase
The enzyme thymidine kinase (TK) is hardly detectable in normal cells, but levels increase sharply in proliferating cells such as cancers. Additionally, since TK activity is highly associated with cell proliferation, it may be a good measure of tumor aggressiveness, and of cell growth that is unregulated. Furthermore, changes in TK activity can appear within two-four weeks of starting cancer treatment.1 Biovica’s DiviTum® is a new and innovative assay that is based on measuring TK activity in blood serum from a routine blood sample.
Key advantages of the DiviTum®TKa assay
DiviTum®TKa is an innovative biomarker assay developed with the aim to monitor treatment response in cancer therapy. The test measures the activity of the enzyme thymidine kinase-1 (TK) in blood serum. In normal cells, TK activity is hardly detectable, but in proliferating cells, its levels increase. Since the degree of TK activity is highly associated with the rate of cell proliferation, it is a particularly suitable biomarker for measuring tumor aggressiveness.
DiviTum®TKa measures thymidine kinase activity, a by-product of cell replication
How DiviTum®TKa works
The DiviTum®TKa assay determines enzymatic activity of thymidine kinase (TK) in blood serum samples. During the assay procedure, thymidine is replaced by its synthetic analog bromodeoxyuridine (BrdU), which gets phosphorylated and then incorporated into a synthetic DNA strand fixated in each well of a 96-well ELISA immunosorbent titer-plate.
The extent of BrdU incorporation depends on the TK activity in the serum sample; the more TK activity, the more BrdU is incorporated into the synthetic DNA strands. The synthetic BrdU is then detected with anti-BrdU specific antibodies using the ELISA assay technique. The DiviTum®TKa technology amplifies the signal, enabling the assay to measure TK activity.
Thymidine kinase phosphorylates the nucleoside analogue BrdU to BrdUMP. Additional enzymes further phosphorylate BrdUMP to BrdUTP.
BrdUTP is subsequently incorporated into a solid-phase DNA-strand. Incorporated BrdU is detected using an anti-BrdU monoclonal antibody conjugated to the signal generating enzyme alkaline phosphatase. The level amount of BrdU incorporated over time is proportional to the level of thymidine kinase activity in the sample.
Nisman B, Allweis T, Kadouri L et al. Comparison of diagnostic and prognostic performance of two assays measuring thymidine kinase 1 activity in serum of breast cancer patients. Clin Chem Lab Med. 2013 ;51(2):439-47.