New concept leading to personalised cancer treatment
Several factors (genetic, epigenetic, lifestyle, environmental) come into play to determine how a particular individual responds to the given therapy. The EU-funded 'Integrated chemical synthesis and screening in patient cells' (ICSC) project developed a technology for identifying novel drug candidates using cancer cells isolated from individual cancer patients. The core deliverable of the ICSC project is a newly developed high-throughput (HT) drug discovery technology, ChemoCellomics®. It integrates chemical synthesis and HT cell-based screening in a micro format directly in primary cells from patients. The present ChemoCellomics® format is on polymer beads (300–400 micrometres (µm) in diameter). Active compounds are identified by isolating beads showing activity followed by mass spectrometry-based identification of the bead-associated compounds. In the ICSC project, the beads are replaced by polymer-coated micro particles (250 µm) that are optically encoded. The encoding represents the synthetic history of the individual compounds and replaces mass spectrometry. The small form factor of the micro carriers allows HT screening in the direct cell isolates from patients. Over two and a half years of the project researchers developed optically encoded particles where measurement of biological activity and compound decoding can be done in a DNA microarray reader. They established procedures for chemical library synthesis and cell attachment on optically encoded particles. HT cell-based screening was successfully tested on defined cancerous cells from patients followed by identification of the active compounds. During the project, it became apparent that the ICSC technology could be applied to direct identification of an effective combination therapy in the individual colorectal cancer patient. Medical treatment of colorectal cancer in Europe and the United States includes 10 individual drugs given in combinations of 3–4 drugs. The ICSC concept has been tested on primary tumour cells from patients. In all cases, cells were treated with a combination of either three compounds or different concentrations of the same compound. The testing demonstrated significant differences in drug sensitivity between patients. Application of the new technology will enable oncologists to find the most efficient combination therapy for the individual colon cancer patients. In the future it might enable the identification of novel drugs acting in combination with established cancer treatment regimens to improve patient outcome.
