Pancreatic cancer: New approach to overcoming treatment resistance

A new study led by the Robert Bosch Center for Tumor Diseases in Stuttgart shows how therapy resistance in pancreatic cancer can be prevented or reversed. It may be that the addition of an active ingredient is enough to make previously unsuccessful chemotherapies effective.

Bosch Health Campus | March 2023
BHC / S. Johnsen

Pancreatic tumor cells stained against Keratin-7

Pancreatic cancer remains one of the most fatal cancer diagnoses of all. In Germany, around 21,000 people will be diagnosed with the disease this year. Of these, half will succumb to the disease within the first six months, and only ten percent will survive five years. In addition to late diagnosis, a major hurdle in the treatment of pancreatic cancer is the amazing and unique ability of the tumor cells to resist the effects of treatment by changing their molecular identity.

A new study now gives hope that it may be possible to prevent or reverse the molecular changes that enable tumor cells to resist the effects of certain chemotherapies. The study was led by Dr. Steven A. Johnsen, Scientific Director of the Robert Bosch Center for Tumor Diseases (RBCT) at the Bosch Health Campus, in collaboration with researchers and physicians from the Mayo Clinic in Rochester, Minnesota (USA), and with important contributions from the University Hospitals of Göttingen, Essen, and Bochum in Germany.

Surprising activation of certain genes

The group was able to identify a unique way in which certain genes become active in chemotherapy-resistant pancreatic cancer. In contrast to their initial expectations, the group found that the epigenetic state of the genes associated with therapy resistance was unchanged. Instead, they found that specific regions of the genome that were already active in tumor cells sensitive to therapy suddenly began to find and activate new partner genes, most notably genes required for therapy resistance.

Based on other molecular changes found to be present on these regions of the genome, the group was able to devise different ways to overcome them. "The great value of our work is that our findings allow us to combine certain compounds currently being tested in clinical trials with chemotherapies routinely used in the clinic," Johnsen explains. “According to our results, we hope that just the addition of one further drug, may be sufficient to prevent therapy resistance or restore therapy responsiveness in resistant tumors."

Success is possible only through teamwork

However, he also emphasizes that there is still a long road ahead to take the findings from laboratory research into clinical practice. To achieve this, Johnsen plans to work closely with his colleague, the Clinical Director of the Robert Bosch Center for Tumor Diseases, Prof. Dr. Hans-Georg Kopp, who is also the chief of oncology at the Robert Bosch Hospital. “Overcoming this dreadful disease will require a lot of teamwork. We cannot do this alone,” Kopp said. With the National Center for Tumor Diseases Southwest, which is funded by the German Federal Ministry of Education and Research and includes the Bosch Health Campus as well as the university hospitals in Ulm and Tübingen, Johnsen and Kopp hope to have more and better opportunities to translate research findings like these into clinical practice.