Can cancer cells develop resistance to the treatment?

New Approaches to Resistance to Therapy in Cancer

If tumors start to grow again despite treatment, doctors often have few options to save those affected. This is especially true for cancers that only occur in young children - called neuroblastomas. These are tumors that develop in the pelvis or head area. In Germany there are around 150 new cases every year. The course of the disease is extremely different: Neuroblastomas can regress spontaneously, but they can also progress very aggressively and lead to death. With a severe course of the disease, only about 30 percent of children survive in the long term.

The biggest problem with the treatment: the neuroblastomas become resistant to the therapy. In many cases, the tumor initially shrinks after the first chemotherapy. At a certain point, however, it begins to grow again and reacts worse and worse to treatment. Scientists at the German Cancer Research Center (DKFZ) in Heidelberg have now deciphered the mechanisms of therapy resistance in the “MYC-NET” project funded by the Federal Ministry of Research. It is now her goal to use this knowledge to develop new therapies against cancer.

Why do certain tumor cells survive chemotherapy?

At the beginning of the research there was the assumption that a kind of selection of resistant tumor cells already occurs with the first chemotherapy: While a large part of the tumor cells die as expected, certain cells survive, grow again and form metastases. In order to find out what distinguishes these cells from the others, the researchers continuously observed the growth of individual tumor cells before and after chemotherapy. “In the interplay of experiment and computer simulation, we found out that cancer cells that are in a certain phase of the cell cycle at the start of therapy can survive chemotherapy,” says Thomas Höfer from the German Cancer Research Center, project manager of “MYC-NET”. Above all, cancer cells that are in a resting phase before the next cell division develop resistance to therapy. These cells survive and multiply again.

New Approaches to Improved Therapies

For the researchers, this results in completely new starting points for improved cancer therapies. “Our results suggest that a combination of chemotherapy and new drugs that influence the growth switches of cells could, in the best case, protect children with neuroblastoma from resistance to therapy,” says Höfer. "The most important thing here is the order in which the various therapies are applied." The idea is that the additional active ingredients intervene in the growth of the tumor cells to such an extent that as few as possible of them are in the critical phase of the chemotherapy Cell cycle.

In cooperation with the pharmaceutical company Bayer, the Heidelberg-based company is currently testing several options for such a combination therapy. "In order to make our results quickly applicable to children with neuroblastoma, we concentrate on active ingredients that have already been approved or have been tested in clinical studies," explains doctor and tumor geneticist Frank Westermann, head of the neuroblastoma reference laboratory at the German Cancer Research Center. The researchers hope that their results can also be transferred to other types of cancer.

The scientific success of the “MYC-NET” project was made possible by funding from the Federal Ministry of Research. The joint project of the German Cancer Research Center and the University of Heidelberg was supported with 2.1 million euros from 2012 to 2015 as part of the funding measure "CANCERSYS - Systems Biology in Cancer Research".