220P - Total cell division the ultimate biomarker for personalized medicine in cancer? Updated technology and novel clinical results

Date 30 September 2012
Event ESMO Congress 2012
Session Poster presentation II
Topics Biomarkers
Personalised Medicine
Presenter simon Gronowitz
Authors S.J. Gronowitz1, B. Nisman2, T. Peretz-Yablonski3
  • 1Medical Sciences, Biovica/Rönnerbol Int AB, 75183 - Uppsala/SE
  • 2Oncology, Hadassah University HospitalHebrew University Medical Center, IL-91120 - Jerusalem/IL
  • 3Hadassah University Hospital, IL-91120 - Jerusalem/IL

Abstract

Aim

To compare an updated serum thymidine kinase activity (s-TK) assay to other TK assays, and show results addressing, differentiation related markers, stage, prognoses, and therapy effect in various types of cancers.

Material and methods

S-TK was determined using both gen1 and gen 2 DiviTum assay. These are based on BrdU phosphorylation, with concomitant processing to BrdUTP and its immobilization into a growing DNA-strand immobilized in a 96-well microtiter plate followed by ELISA quantification of DNA amount produced. Serum material analysed comprised both retrospective cohorts and recently collected sera sampled in connection with imaging and/or surgery or other therapy invention in cancer.

Results

Working time of DiviTum assay was reduced from 24h to 7h by use of 2 ul sample per well and modified reaction conditions. Technically less sample dilution and incubation performed at 37oC made the assay simpler to perform and easier to semi automatize. This combined with use of soluble standards increased the reproducibility of the assay. Comparison between the original and the modified DiviTum assay showed similar values for cancer patients as compared healthy individuals.

A better resolution of cancer patients (including breast, lung, prostate and blood malignancies) from healthy individuals was found using DiviTum, as compared to REA-TK assay or nonradioactive Liason TK assay. Further, in healthy carrying BrCa mutation, or benign breast lumps increased levels of cell division was detected with DiviTum assay but not Liason TK assay. A strong relation between s-TK and finding of metastases was seen when comparing pretreatment s-TK with imaging for different types of cancer. The effect of various therapies, including surgery, thermal ablation and various chemotherapies upon cell division measured by DiviTum TK in patients with spread cancer will be presented to illustrate the capacity of the improved assay.

Conclusion

S-TK by DiviTum principle detects 10 times less tumor cell division the other TK analyses due to low signal from healthy. This makes total body cell division analyses a useful parameter also for solid cancers. However, for the implementation in daily practice more clinical research addressing all types of cancer is required.

Disclosure

S.J. Gronowitz: J. Simon Gronowitz is the inventor of the DiviTum assay and his family owns stock shares in Biovica International AB. In addition he is the research director and a meber of the Board of said company.

All other authors have declared no conflicts of interest.