Metabolomics to investigate combined cancer therapy

Breast cancer is the leading type of cancer in women worldwide and accounts for about 25% of all cases with steadily increasing rates. Most breast cancers require estrogens for their growth and risk factors for this disease include also exposure towards estrogens through the diet or the environment. In the research project Metabolomics to investigate combined cancer therapy the molecular basics of a novel, highly promising anti-cancer drug (palbociclib) will be investigated in detail. The combined treatment with a current standard anti-cancer drug as well as the impact of two estrogens which occur naturally in our food will be evaluated. Thereby, we intend to better understand the mode of action of the combined treatment. The effect of the dietary estrogens will be studied to prove whether or not they influence this therapy. To measure the response of breast cancer cells on the different treatments we will use highly innovative and comprehensive analytical platforms, which are able to detect thousands of small molecules simultaneously. These so-called metabolomics platforms will enable us to directly look into the metabolism of cancer cells. A novel technique, the global isotope metabolomics approach will be applied for the first time in cancer research within the course of this project. It is expected that the project results in a deeper knowledge of the mode of action of the novel combined breast cancer treatment and the impact of dietary estrogens. As a long-term goal it is hoped that the new insights will contribute to enhance future anti-breast cancer drug developments and therapies.

Breast cancer is the leading type of cancer in women worldwide and accounts for about 25% of all cases with steadily increasing rates. Most breast cancers require estrogens for their growth and risk factors for this disease include also exposure towards estrogens through the diet or the environment. In the research project Metabolomics to investigate combined cancer therapy the molecular basics of a novel, highly promising anti-cancer drug (palbociclib) was investigated in detail using innovative mass spectrometry and cloud-based data processing methodology. The combined treatment with a current standard anti-cancer drug (letrozole) as well as the impact of two estrogens which occur naturally in our food were evaluated. To measure the response of breast cancer cells on the different treatments we used highly innovative and comprehensive analytical platforms, which were able to detect a myriad of small molecules simultaneously. These so-called metabolomics platforms enabled us to directly look into the metabolism of cancer cells. Applying these new techniques, we found that amino acid metabolism, the central energy metabolism and lipid metabolism are the key points of significant alterations upon the combined cancer therapy. Moreover, we saw a very distinct effect of two model dietary estrogens, the plan hormone genistein and the mycotoxin zearalenone, on several of the affected metabolites. The project resulted in a deeper knowledge of the mode of action of the novel combined breast cancer treatment and the impact of dietary estrogens. As a long-term goal it is hoped that the new insights gained will contribute to a more effective development of breast cancer therapies and lead to science-based nutritional recommendations for cancer patients.