FACT is a blood test which measures a nucleic acid biomarker released from dying cancer cells. The FACT test can be performed regularly during chemotherapy treatment. An inadequate decrease in the cell free telomere level could alert the testing oncologist to possible ineffective treatment. By collapsing the amount of time required for treatment efficacy assessment, Blondin Bioscience will contribute to reducing the overall cancer burden for patients.
Speeding the time to knowledge will reduce the emotional expenditure, financial burden, potential side effects from ineffective drugs, and perhaps most importantly, the time required to find the optimal treatment protocol. In short, we hope to save lives. Learn more by listening to Blondin Bioscience’s interview with Birmingham Business Radio or by reading Kirti Patel’s blog post
Telomeric DNA is over-expressed in cell-free DNA from cancer cells. This cell-free telomeric DNA (cf-tel DNA) is preferentially secreted by cancer cells relative to healthy cells, thus cf-tel is a measure of tumor burden. Blondin’s novel DNA capture technology (developed by Dr. Kate Hayden and collaborators) allows for specific quantification of cf-tel DNA using proprietary tests developed at Blondin. A pilot clinical study of the ability of cf-tel DNA to predict clinical response in metastatic prostate cancer is underway at UAB Medical Center. Expansion of this study to Duke, Vanderbilt, Emory and 3 other academic medical centers is planned in a SBIRPhase 2 application to the NIH. Similar clinical studies in metastatic non-small cell lung cancer, triple negative breast cancer, and metastatic colon cancer are planned for the future.
In other Blondin research, Dr. Katri Selander, has been investigating TLR9 as a source of health care disparity in triple negative breast cancer. She has previously found that high TLR9 (an important protein in the innate immune system) is associated with good prognosis in Caucasian patients, but not in African-American patients. She has identified genetic differences in the TLR9 gene between these two ethnic groups that may be the cause of this difference in protection by TLR9. She has submitted an NIH R21 application to the Institute on Minority Health and Health Disparities to study the effect of these genetic changes. Also, she will determine if bisphosphonate drugs can overcome the inability of high TLR9 to support a good prognosis in African-American patients. This work could lead to additional Blondin commercial products such as TLR9 clinical diagnostics, and a novel bisphosphonate drug to treat triple negative breast cancer.
1. Estrogen receptor-α and sex steroid hormones regulate Toll-like receptor-9 expression and invasive function in human breast cancer cells.Sandholm J, Kauppila JH, Pressey C, Tuomela J, Jukkola-Vuorinen A, Vaarala M, Johnson MR, Harris KW, Selander KS. (2012).Breast Cancer Res Treat. Apr;132(2):411-9,
2. Low TLR9 expression defines an aggressive subtype of triple-negative breast cancer.Tuomela J, Sandholm J, Karihtala P, Ilvesaro J, Vuopala KS, Kauppila JH, Kauppila S, Chen D, Pressey C, Härkönen P, Harris KW, Graves D, Auvinen PK, Soini Y, Jukkola-Vuorinen A, Selander KS. (2012). Breast Cancer Res Treat.135(2): 481-93,.
3. DNA from dead cancer cells induces TLR9-mediated invasion and inflammation in living cancer cells Tuomela J, Sandholm J, Kaakinen M, Patel A, Kauppila JH, Ilvesaro J, Chen D, Harris KW, Graves D, Selander KS. (2013) Breast Cancer Res Treat. Dec;142(3):477-87.
4. Hypoxia regulates Toll-like receptor-9 expression and invasive function in human brain cancer cells in vitro. Sandholm, J., Tuomela, J., Kauppila, J. H., Harris, K. W., Graves, D., and Selander, K. S. (2014), Oncology Letters 8, 266-274.
5. Toll-like receptor 9 expression is associated with breast cancer sensitivity to the growth inhibitory effects of bisphosphonates in vitro and in vivo. Sandholm, J., Lehtimaki, J., Ishizu, T., Velu, S.E., Clark, J., Harkonen, P., Jukkola-Vuorinen, A., Schrey, A., Harris, K.W., Tuomela, J.M. et al. (2016) Oncotarget. Dec 27;7(52):87373-87389 (2016)
6. Telomeric G-quadruplex-forming DNA fragments induce TLR9-mediated and LL-37-regulated invasion in breast cancer cells in vitro. Tuomela, J.M., Sandholm, J.A., Kaakinen, M., Hayden, K.L., Haapasaari, K.M., Jukkola-Vuorinen, A., Kauppila, J.H., Lehenkari, P.P., Harris, K.W., Graves, D.E. et al. (2016) Breast Cancer Res Treat, 155, 261-271.
7. Isolation and purification of cell-free human telomeric DNA using peptide nucleic acid (PNA) capture probes. Hayden K, Gupta A, Armitage B, Selander K, and Graves D. (2017) In preparation for submission to Biochemistry
8. Cell-free telomeric DNA is associated with breast cancer proliferation and death.
Tuominen, S., Habash, M., Hayden, K.,Jukkola-Vuorinen, A., Harris, K.W., Tuomela, J.M., Selander,
K.S. (2017) Manuscript submitted.
9. Cell-free telomeric DNA is released from patients with acute myeloid leukemia in response to chemotherapy-induced cell death. Borate U., Hossain EM, Metha A, Pressey C, Ousley RJ, Bartlett T, Dhulipala V, Stoltz KM, Graves D, Selander KS, and Harris KW. (2017) Manuscript submitted