Monitoring spreading cancer cells as a basic research and diagnostic tool
Christer Ericsson, PhD, Department of Microbiology, Tumor- and Cell Biology (MTC), Karolinska Institutet, Stockholm, Sweden
In 1869, Thomas Ashworth, the a resident physician at Melbourne Hospital Australia, observed for the first time cells that were morphologically identical to cancer cells observed in a postmortem blood sample from a patient who had about 30 subcutaneous tumors, cells that were morphologically identical with the cancer cells. This observation prompted him to suggest suggest that they the cells “may tend to throw some light upon the mode of origin of multiple tumors existing in the same person”. Circulating tumor cells (CTC) are likely to be the particles that seed s metastasis as already suggested 1454 years ago. Consequently, since 90% of the deaths are associated with metastases, the to study of the spread of cancer is important. If CTCs indeed turn out to be the cells responsible for the spread of cancer, as seems to be the case, or if they reflect important aspects of the diversity of the cancer cells, then it is important to study their properties, whether for basic research or as a diagnostic tool.
However, the primary tumor biopsy has remained the basis for cancer diagnosis, as it was difficult to develop a research or diagnostic test based on Thomas Ashworth’s early insights.
Major reasons for the lag in developing the 144-year-old insightsinsight based on the detection of circulating tumor cells (CTCs) are:
The extremely low number of CTC cells (10-6 or lower in frequency) against a background of normal blood cells
Heterogeneity and plasticity of CTCs with subpopulations that have lost characteristic epithelial features including cell-surface markers
We have developed a sensitive assay for identification of to identify and isolate CTCs, which is independent of any lost biological surface featuresmarkers.
A first pOur preliminary proof-of-principle tests forof the clinical relevance showed that we could indeed monitor the response to colorectal surgery in combination with advanced adjuvant therapy. Consequently, isolation, quantification and molecular analysis of CTCs is seems to be a valuable addition to the scientific and diagnostic repertoire. This, new test which should subsequently will lead to large significant improvementssignificant improvements in the efficacy of cancer care.
Supported by the Karolinska Institutet innovation system, we have therefore started theestablished our company Liquid Biopsy AB (www.liquid-biopsy.com) in 2011NN to market an instrument for the isolation of rare, heterogenous and plastic CTCs for basic and translational research.
Ashworth, T. R (1869). "A case of cancer in which cells similar to those in the tumours were seen in the blood after death". Australian Medical Journal 14: 146–7
Castro J., Ericsson, C., Cashin, P. and Mahteme, H. (2012). “Preliminary Finding: Detection of Circulating Cancer Cells in Blood from a Patient with Peritoneal Carcinomatosis Treated with Cytoreductive Surgery and Intraperitoneal Chemotherapy”. Surgery Curr Res 2:113.
Academic honours, awards and prizes
The Florman award by the Swedish Royal Academy of Sciences