Breast cancer

Breast cancer is the most common cancer in women worldwide. There is a need for new biomarkers to measure the effectiveness of treatment and the efficacy of new drugs candidates in clinical trials. TK1 is a strong candidate as it measures proliferation and cell disruption, and as samples can be collected as easily by a blood sample.

Breast cancer is the most common cancer in women worldwide. There are several risk factors associated with breast cancer including age, family history, reproduction, mammographic density, exposure to various agents such as alcohol and radiation, and the use of combined estrogen/progestogen contraceptives.

There were an estimated 1.7 million new cases globally in 2012 and 522 000 deaths caused by this disease. Europe and North America represents 43% of the incidences but only 35% of the deaths¹. Incidences increased as an effect of introducing mammography screening as well as an ageing population. Mortality rates have been declining in the western word since the 1980s due to a combination of improved detection sensitivity, population-based screening, and improved treatment².

Pre-operative chemotherapy plus the addition of irradiation and hormone therapy has increased survival rate after surgery (mastectomy) to treat breast cancer. Researchers are continuously looking for new ways to improve survival, in particular for patients contracting metastatic diseases². A recent addition to the therapeutic arsenal is cycline-dependent kinase (CDK) inhibitors. These drugs work by inhibiting CDK 4 or CDK 6. Overactivity of kinases facilitates the proliferation of cancer cells. The CDK 4/6 inhibitors cause cell cycle arrest but these new drugs can be expensive and may cause side effects.

AroCell aims to offer a robust, reproducible and cost-effective assay for monitoring breast cancer patients during treatment and for surveillance of patients after treatment. The objective is to help clinicians obtain more information by measuring the outcome of the treatment as well as to provide decision support in disease management.

TK1 as biomarker in breast cancer

There is a need for new biomarkers to measure the effect of treatment, as well as the efficacy of new drug candidates in clinical trials³.

TK1 is a candidate; measured in the cell it indicates the rate of cell proliferation, measured in blood it indicates the disruption of proliferating cells. In breast cancer, proliferating cells disrupt spontaneously or as a consequence of anti-tumoral therapy.

Kumar et al. suggest that AroCell TK 210 ELISA can detect significant differences in the levels of TK1 in sera from patients with breast cancer at different stages as compared to non-breast cancer controls4. Moreover, significant differences were observed between TK1 levels in patients with lymph node involvement and metastatic disease compared to those without. The results are consistent with the notion that AroCell TK 210 ELISA can be used for monitoring breast cancer in late-stage disease. In addition, correlation between AroCell TK 210 ELISA and activity-based methods was high4.

 

 

TK1 activity and protein concentration levels in sera from healthy and from the entire breast cancer groups. A: Log TK1 activity levels in sera from breast patients and healthy individuals. B: Log TK1 protein concentration levels in sera from healthy and breast cancer patients. Error bars denote maximum and minimum values. The receiver operating characteristic (ROC) curves C: TK1 activity assay. D: AroCell TK 210 ELISA for breast cancer patients in comparison with healthy individuals4.

 

  1. Stewart B.W. and Wild C.P. (Eds) World Cancer Report 2014. World Cancer Reports. World Health Organization. ISBN (PDF) 978-92-832-0443-5; ISBN (EPUB) 978-92-832-0432-9
    http://publications.iarc.fr/Non-Series-Publications/World-Cancer-Reports/World-Cancer-Report-2014
  1. Bjöhle et al.,Serum Thymidine Kinase activity compared with CA 15-3 in local advanced and metastatic breast cancer within a randomized trial. Breast Cancer Res Treat 139 (2013), 751-758 Doi 10.1007/s10549-013-2579-x
    https://www.ncbi.nlm.nih.gov/pubmed/23736998
  1. Kimbung, S. et al., Assessment of early response biomarkers in relation to long term survival in patients with HER2 negative breast cancer receiving neoadjuvant chemotherapy plus evacizumab: Results from the Phase II PROMIX trial. Int J Cancer,142(3) (2018). 618628.doi: 10.1002/ijc.31070. Epub 2017 Oct 13
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5765477/
  1. Jagarlamudi, K.K. et al.,A clinical evaluation of the TK 210 ELISA in sera from breast cancer patients demonstrates high sensitivity and specificity in all stages of disease. Tumor Biol. Published online 14 April 2016.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5080325/