Pancreatic cancer Specific enzyme is the cause of cancer tumor resistance

Cause of the treatment resistance of pancreatic cancer cells discovered
Pancreatic cancer is one of the most malignant cancers. The prospects for a successful treatment are extremely bad today. Scientists at the German Cancer Research Center (DKFZ) and the stem cell institute HI-STEM in Heidelberg have now discovered why some pancreatic tumors are so resistant to treatment. Obviously, the tumor cells produce larger amounts of an enzyme that breaks down many drugs and actually occurs in the liver. Blockade of the enzyme could significantly increase the efficacy of pancreatic cancer therapy. The researchers published their latest study results in the journal "Nature Medicine".

The scientists of the DKFZ and the HI-STEM stem cell institute not only discovered that the enzyme protects the tumor cells from the effects of the drugs, but they also showed that the cancer cells become sensitive to the therapy again if the enzyme is blocked. In addition, the researchers have developed a "clinically feasible test", "with which three types of tumors can be detected with different disease course," says the DKFZ.

Pancreatic cancer tumor cells become resistant to the action of drugs through a special enzyme. (Image: Coloures-pic / fotolia.com)

Prognosis for pancreatic cancer is usually poor
For those with a diagnosis of pancreatic cancer (pancreatic cancer), the prognosis is usually very poor. Not infrequently, they have only a few months to live after finding the disease. "This is usually because the disease is often discovered only when the tumor has already metastasized and at this time an operation no longer makes sense," says the DKFZ. In addition, many of the tumors are resistant to chemotherapy. The recently discovered three different types of pancreatic tumors differ in their aggressiveness, but also in their response to drugs, according to one of the results of the current research by the research team led by Andreas Trumpp and Martin Sprick from the DKFZ and the stem cell institute HI-STEM.

Enzyme helps in the breakdown of the drugs
In their study, the researchers found that the tumor cells of the resistant subtypes increasingly produce the enzyme CYP3A5, which is normally active in the liver. According to first author Elisa Noll, "the pancreatic tumor cells take advantage of this enzyme cascade and break down drugs before they can even work." In this way, the cells would be resistant to many currently used cancer drugs. According to Martin Sprick, researchers "have already succeeded in blocking the enzyme in the tumor cells and even in tumor-bearing mice, thereby making the cells sensitive to the drugs." Scientists now hope to find substances which can also be used in human patients.

Resistance in response to the treatment?
According to the researchers, "CYP3A5-mediated drug resistance in cancer cells can only occur in the course of treatment." The tumor cells thus respond to practically the drugs used. Although "about twenty percent of pancreatic tumors are resistant from the outset due to the production of this enzyme," it can be assumed "that secondary resistance plays a role in even more patients," emphasizes Martin Sprick. The researchers substantiate this assumption with the observed response of the cancer cells to the prolonged administration of the drug paclitaxel. Previously sensitive tumor cells had suddenly produced more CYP3A5 and then no longer addressed the treatment, reports the DKFZ.

According to the scientists, the detected enzyme could also reduce the effectiveness of the therapy in other cancers. For example, evidence of CYP3A5-mediated drug resistance has also been identified in gastric carcinoma and liver cancer, the DKFZ reports. The previously unknown mechanism may also play a role in the failure of individual clinical trials. (Fp)