Thymidine Kinase 1 (TK1) as a biomarker for therapy response in treatment of breast cancer patients

Breast cancer is the most common cancer among women. Although the breast cancer mortality rates have fallen over the past few decades – thanks to early detection and treatment improvements – the disease remains the second leading cause of cancer death in females.

A key element in the management of treating cancer is to monitor how well a given therapy is working. At present, monitoring relies heavily on imaging techniques, including magnetic resonance imaging (MRI), positron emission tomography (PET) and computed tomography (CT). Imaging methods are expensive and time-consuming and typically provide information on treatment response after the patient has completed a particular treatment. As a complement to the imaging methods – biomarkers, substances that are made by the tumor or by the body in response to cancer – can add information about the treatment effect. When studying biomarkers in tumor tissue, a biopsy is often taken from a part of the tumor, which means that the whole tumor is not represented in the sample.

Thanks to new techniques, doctors may soon be able to monitor breast cancer and assess prognosis with a simple blood test. Actually, already today, some blood-based assays are helpful in monitoring therapeutic response, including the most widely used serum biomarkers 15-3 (CA 15-3) and carcinoembryonic antigen (CEA). Thymidine Kinase 1 (TK1) is an attractive candidate for monitoring response to breast cancer treatment and detecting relapsed cancer after the treatment is over. With AroCell’s new blood test TK 210 ELISA, TK1 levels can easily be measured in blood samples from cancer patients. TK1 is a protein in close association with DNA synthesis and cell proliferation and its levels are elevated in the blood of patients with a wide variety of solid tumors, including breast tumors (O’Neill, Buckwalter, & Murray, 2001). Increased levels of TK1 in the blood is an early event in cancer development, and the levels increase with the grade and stage of the disease (Jagarlamudi & Shaw, 2018; RA, 2013). TK1 assessment is of low cost can easily be carried out with any frequency of the monitoring.

TK1 has the potential to be of great value for early prediction of treatment for patients with breast cancer. Patients treated with Epirubicin and Docetaxel before surgery were followed by their TK1 levels in serum to directly observe treatment response (Tribukait et al., 2017). In the study, it is concluded that serum TK1 levels are a valid marker for tumor cell loss during NACT (neoadjuvant treatment). In another study, patients were treated with the cyclin-dependent kinase 4/6 (CDK4/6) inhibitors (Bagegni et al., 2017; McCartney et al., 2019). Where the data is supporting that TK1 can be a prognostic and monitoring marker of advanced breast cancer when treated with endocrine therapy, and potentially enabling clinician to early identify treatment resistance and switch to a more efficient one, rather than waiting for treatment failure (McCartney et al., 2019).

Hence, TK1 concentration in serum samples appear to be a promising tool for early treatment response and prediction of the outcome of treatment for breast cancer patients.

Regardless of the treatment given, some patients are resistant to the therapy already from the start, whereas other patients eventually develop resistance. Measuring the TK1 concentrations in blood may aid clinicians at an early time point to identify patients who are resistant to treatment. This will result in better treatment outcome for the patients, as therapies can be changed quickly if not working. In addition, unnecessary side effects can be avoided and money saved when effective treatments can be identified in this way.

Summary:
New breast cancer therapies are offering hope and possibilities to patients with spread disease. In comparison with currently available monitoring techniques, a liquid biomarker such as TK1 is a unique marker to obtain early evidence of treatment response, which is crucial in the fight against cancer.

References:
Bagegni, N., Thomas, S., Liu, N., Luo, J., Hoog, J., Northfelt, D. W., . . . Ma, C. X. (2017). Serum thymidine kinase 1 activity as a pharmacodynamic marker of cyclin-dependent kinase 4/6 inhibition in patients with early-stage breast cancer receiving neoadjuvant palbociclib. Breast Cancer Res, 19(1), 123.

Jagarlamudi, K. K., & Shaw, M. (2018). Thymidine kinase 1 as a tumor biomarker: technical advances offer new potential to an old biomarker. Biomark Med, 12(9), 1035-1048.

McCartney, A., Biagioni, C., Schiavon, G., Bergqvist, M., Mattsson, K., Migliaccio, I.,. Malorni, L. (2019). Prognostic role of serum thymidine kinase 1 activity in patients with hormone receptor-positive metastatic breast cancer: Analysis of the randomised phase III Evaluation of Faslodex versus Exemestane Clinical Trial (EFECT). Eur J Cancer, 114, 55-66.

O’Neill, K. L., Buckwalter, M. R., & Murray, B. K. (2001). Thymidine kinase: diagnostic and prognostic potential. Expert Rev Mol Diagn, 1(4), 428-433.

Tribukait, B., Jagarlamudi, K., Bergh, J., Hatschek, T. (2017). Quantitation of Cell Loss in Breast Cancer during Neoadjuvant Treatment (NACT) Assessed by Serum Thymidine Kinase Protein Concentration (sTK1). Poster from European Society for Medical Oncology (ESMO).