CTCtrap – Circulating Tumor Cells TheRapeutic APheresis: a novel biotechnology enabling personalized therapy for all cancer patients

Final Report Summary CTCTRAP (Circulating Tumor Cells TheRapeutic APheresis: a novel biotechnology enabling personalized therapy for all cancer patients) Executive Summary: Chemotherapy is slowly being supplemented by a new generation of drugs that recognize specific targets in or on cancer cells and has proven to be more effective with markedly fewer side effects. During the course of the disease alternative oncogenic signaling pathways take over inevitably leading to drug resistance. As a consequence renewed tumor analysis is required to redefine the optimal treatment regiment. However a biopsy can frequently not be obtained without risk and / or discomfort to the patient. Circulating tumor cells (CTC) may circumvent this problem. CTC refer to cells that detach from a primary tumor or metastatic site, circulate in the peripheral blood and may form metastasis. CTC represent a "liquid biopsy" that can be used to tailor treatment for individual patients. CTC are however rare and can only be obtained for further characterization in a small fraction of patients. In the CTCTrap consortium universities, research institutions and SMEs have explored various ways to isolate CTC from 1-2 liters of blood. The approach ultimately evaluated in cancer patients was Diagnostic LeukApheresis (DLA) in combination with the FDA cleared CellSearch system targeting EpCAM+ CTC and technology based on differences in physical characteristics between blood cells and cancer cells (EpCAMCTC). This approach has led to a significant increase in the number of isolated CTC enabling a more comprehensive real-time characterization of the cancer. Development is however still ongoing to further improve the CTC enrichment in conjunction with DLA. Using the technology developed in CTCTrap EpCAM+ as well EpCAMCTC were identified in both prostate as well as breast cancer patients. Long-term follow-up will be needed to determine the relation with clinical outcome. Efforts are still ongoing to gather new knowledge on the differences at both the molecular and protein level of these CTC. These results will provide insight in the mechanism of metastasis, provide a risk assessment and guide the optimal therapy choice for the patients. Pilot work on the health economic consequences of the use of CTC’s in cancer disease management has been conducted. Although the value of diagnostics generally is appreciated, the current incentive structures do not facilitate nor reward innovation in diagnostic testing. Diagnostic testing is seen as part of the value created by drugs and current reimbursement schemes do not easily incentivize further developments nor implementation of diagnostics. For this reason, it is very useful to anticipate market access and reimbursement in case of advanced molecular diagnostics, such as developed in the CTCTrap program.