The results will now have to be verified for humans in controlled prospective studies. Subsequently, it will have to be decided whether the treatment guidelines for a number of solid tumors need to be modified. Until then, it is strictly advised not to terminate ongoing therapies with cortisone drugs without consulting the doctor in charge.

Cortisone drugs used in cancer treatment cause programmed cell death, or apoptosis, in transformed cells of the hematopoietic system. In addition, the drugs lessen side effects such as nausea and vomiting and protect against edema formation as well as allergies to specific chemotherapy drugs. At the same time, glucocorticoids protect normal body tissue against harmful side effects of the tumor. These facts have given the drugs a good reputation. The recommendations for cancers of the blood have so far also been applied to the treatment of carcinomas by leading oncological organizations. However, sufficient controlled studies have not yet been performed for this area of application.

In a diversified investigation of cells from over a dozen types of cancer including tumors of the lung, breast, prostate, colon, pancreas, and nerve tissue, Ingrid Herr and clinicians of Heidelberg University Hospital have now confirmed a suspicion that arose back in mid-2003. Jointly with colleagues from Ulm and Heidelberg, Herr had shown at the time that cell lines from cervical and lung cancers respond significantly less well to drug treatment or irradiation when glucocorticoids are given at the same time. The researchers put this down to a change in the apoptosis program. For reasons that are not yet known, substances of the steroid hormone group block programmed cell death in solid tumors, while inducing apoptosis in malignant blood cells.

Does this effect occur only in individual malignant tumors or is this a general mechanism? To answer this question, the Heidelberg researchers analyzed more than 150 tissue samples of representative cancers using common cell lines, freshly isolated tumor tissue cells and tumors that had been transplanted into mice. They found out that over 85 percent of tumors studied develop a resistance and, thus, become less sensitive to numerous tested anticancer drugs and radiation when steroid hormones are given at the same time. The effect was observed for various common glucocorticoids and at very low levels and lasted for quite some time even after a single dose. In addition, tumors appear to grow faster under these conditions.

Ingrid Herr recently published these results in five individual publications. The scientist has now compared these to data from other research projects and provided a summary in an article in the specialist journal Lancet Oncology. It turned out that over 50 years ago researchers had already observed increased metastasis in breast cancer patients who received cortisone drugs. Elevated levels of endogenous glucocorticoids, which often occur in patients with renal cell carcinoma, were found to correlate with a worsening prognosis. Patients with brain metastases of a primary lung tumor responded less well to cancer treatment when they received steroid hormones at the same time. These are alarming results. On the other hand, a retrospective study showed no negative effects of cortisone drugs on the survival of ovarian cancer patients. However, the results of a further patient study indicate that systemic treatment with steroid hormones also appears to increase the risk of skin cancer or lymphoma. Researchers presume that the development of therapy resistance and the increased tendency to metastasize of solid tumors under glucocorticoid treatment may be caused not only by inhibition of apoptosis, but also by a weakening of the immune system.

However, scientists emphasize that it is too early to condemn glucocorticoid therapy altogether, since it also has many positive effects in cancer treatment. It is necessary to verify the assumptions reached from investigations with cell lines and animals in controlled prospective studies. This is the topic of ongoing research projects.

About the DEUTSCHES KREBSFORSCHUNGSZENTRUM

The Deutsches Krebsforschungszentrum (DKFZ) Heidelberg was founded as a non-profit organization and supraregional research center by the Land (state) Baden-Wuerttemberg in 1964. It was constituted as a foundation of public law. Since 1975, it has been a Gro?forschungseinrichtung (National Research Center). It is mainly funded by the Bundesforschungsministerium (Federal Ministry for Research and Technology) (90 %) and by the Ministerium fuer Forschung und Wissenschaft (Ministry for Research and Sciences) of the Land Baden-Wuerttemberg (10 %). Additional funding is obtained by other public and private sources e.g. the Deutsche Forschungsgemeinschaft (German Science Association), special projects of the European Union (EU), of Federal and State ministries as well as cooperations with the industry and also private donations to the foundation. In accordance with its Statutes and Articles, it is the task of the Center to engage in cancer research. "Cancer research", a term which every discipline defines quite differently. In a center with a multi-disciplinary structure, the discussion about the research program is a continuous balancing process.

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