Getting Closer - Novel Possibilities to Evaluate Cancer Drugs Using Human Cancer Stem Cells

Within the next 30 years the WHO and the RKI in Germany predict an increasing rate of cancer. The need for effective therapies/diagnostics is higher than ever. Here we present a cost saving method that uses blood of cancer patients to detect more effective substances in the preclinical phase. To get a substance from the preclinical phase to initial clinical trials is a time consuming and expensive process. Even when they reach the clinical phase most of the drugs will not come onto the market. Often the effectiveness of drugs cannot be reproduced in human patients, which was seen in xenograft models or cells lines. Even therapies with confirmed efficiency do not work for every patient: This may be due to the patient's tumor stem cells exhibiting better mechanisms of resistance than other tumor cells. Although in vitro methods will never really reflect the physiological/pathological processes in the human body a model as close as possible to reality will enable the researcher to gain a realistic picture. This would provide a higher probability for the tested drug to become successful in later clinical phases. Therefore, we developed a method to culture tumor stem cells (tumorspheroids) from blood samples of cancer patients. The ability of some of the circulating tumor cells to form tumorspheroids and the surface marker expression profile of the cells in the spheroids are typical for cancer stem cells. In breast cancer patients the tumorspheroids are positive for EpCAM, low or negative for CD24 and highly positive for CD44 and express a high level of ALDH1. Tumorspheroids from colorectal cancer are positive for EpCAM and CD133. The number of tumorspheroids correlates significantly with the aggressiveness of the disease. Interestingly the tumorspheroids showed a much higher resistance against some of the common cancer therapeutics compared to the other circulating tumor cells. Only salinomycin, a drug that is known to target especially tumor stem cells, was able to eliminate tumorspheroids. This approach will provide a promising new method towards a more realistic setting in the preclinical phase. Email: [e-mail]