Background Natural substances and micronutrients are more and more included in anti-cancer therapy. However, benefit and harm both are reported from one and the same substance. This emphasizes the urgent need for the systematic analysis of a personalized approach which patient will profit from which substance.

Materials and Methods Risk analysis was performed using PBMCs isolated from patients diagnosed with advanced solid cancer. Benefit was analyzed using 3D-microtumors directly prepared from individual patient tumors. Blood cells and cancer cells were treated with different natural substances, namely curcumin, artesunate and vitamine C, as single agents and in combination therapy with guideline-directed drugs for 72h. Impact on cell metabolic activity was measured with the CellTiter Glo assay. The cell phenotype was described by FACS analysis.

Results In 80% of the patients natural substances induced a slight (mean: 10.7%, range: 2.3–17.7%) metabolic inhibition of the immune cells, which was minor in comparison to the strong immunotoxicity of chemotherapeutic drugs (e.g. 5-FU, mean: 33.5%; Gemcitabine: 67.2%). Contrary, 20% of the patients revealed a stimulatory effect on PBMC depending on the basic activity and the exhaustion of the immune cells. Combination therapy revealed that natural substances were able to reduce (mean: 16.4%, range: 5.2–42.8%) immunotoxicity mediated by chemotherapy. Analysis of the 3D-microtumors indicated that natural substances can mediate an anti-cancer effect, which was most obvious in relapsed tumors heavily pretreated with chemotherapeutic drugs. In addition, natural substances were identified as chemosensitizer. For example, curcumin was found to increase efficacy of Mitomycin C in breast cancer, Bicalutamid in prostate cancer and 5-FU combined with Cisplatin in gastric cancer.

Conclusions Complementary substances have a different effect depending on dosing, timing, cell type and cell characteristics. Therefore preclinical testing is required to identify the most effective complementary substances for the individual cancer patient analyzing both immune cells and cancer cells.

Disclosure Information M. Luzbetak: None. N. Süßenguth: None. E. Kronemeyer: None. H. Widera: None. J. Werner: None. B. Mayer: None.