The elimination of a cancer stem cell
The research program of the LBI HO is based on the concept of cancer stem cells built on the assumption that each tumor and each leukemia consists of two functionally different parts, namely a stem cell fraction and more mature tumor cells.
The decisive factor here is that only the tumor stem cells are capable of unlimited multiplication, whereas the more mature daughter cells in the tumor (or leukemia) usually die by themselves after a variable number of cell divisions (as well as normal tissue cells). The aim of any sustained cancer therapy must therefore be to eliminate not only the more mature tumor cells, but also the tumor stem cells, which are therefore to be regarded as the root of the cancer diseases. These cells must be destroyed so that no further multiplication can occur and no further daughter cells are produced. The main problem is the high resistance of the cancer stem cells and the fact that they have so far hardly been tested for their biological and molecular properties, which is mainly due to the fact that they represent a small sub-fraction of the tumor and that it is usually very difficult to isolate these cells and to study them in the laboratory.
First, the stem cell population must be separated from the main pool of the cells and isolated as neatly as possible. Subsequently one has to identify genes which provide the cancer stem cells with their special properties. Only then can the stem cell-specific genes and their products be attacked with the approaches of the targeted cancer therapy. First successes with leukaemias rise hope that the stem cell-directed therapy approaches will ultimately also be successful in solid tumors.
To date, the genes or proteins that are responsible for the increased survival of the cancer stem cell are not clearly identified neither in leukaemias nor in solid tumors. To characterize them, cancer stem cell and “progeny cells” are isolated and compared separately.
The “Achilles heel” of the cancer stem cells is the main target of these investigations. Regulatory pathways, mechanisms and structures that play a role in stem cell biology and the maintenance of self-renewal potential, but are also responsible for survival strategies and resistances of cancer stem cells are potential targets for the development of “targeted” therapies. On the basis of these findings, therapeutic approaches and new drugs for the elimination of cancer stem cells can be developed.
From the hospital bed to the lab – and maybe back again:
Tumor stem cell research is a prime example of successful collaboration between preclinical fundamental research and clinical medicine. The results of molecular cell and tissue research are quickly translated into the development of new strategies for cancer treatment, which are tested on the patient and, if necessary, refined for further improvement in the laboratory.