Researchers find more effective pathway for cancer cells to die

Our research into a long-established chemotherapy drug has uncovered a more successful way of killing cancer cells.

The findings could offer valuable new insight into developing more successful drugs to treat advanced colon, pancreatic and other cancers.

Published in the journal Cell Death and Differentiation, the research looked at the drug Fluorouracil (5FU) which has been used in various forms as a chemotherapy treatment. It is effective in killing cancer cells for a period of time but after a while it frequently fails, and the cancer cells start growing again and the drug becomes ineffective.

The researchers, led by Dr Ralf Zwacka, from the University’s Cancer and Stem Cell Biology
Group, looked into the mechanisms of how the cells are killed and identified the protein Caspase-10 as one of the factors involved in the cancer cell killing process triggered by 5FU.

To better understand the working of this protein, the team genetically-engineered cells without Caspase-10, expecting there to be less cell death. However, the opposite was true and the scientists saw higher cell death in cancer cells. They discovered the engineered cells were switching to a different way of dying, which involved the production of cytokines, including one called tumour necrosis factor (TNF). These proteins were responsible for triggering cell death and also brought the immune system into play, helping in the process of destroying the cancer cells. The overall effect of the treatment with 5FU was now more successful.

“Initially these findings were very surprising,” explained Dr Zwacka, “but they open up some interesting new therapeutic avenues for improving the treatment of advanced cancers.”

This study was part of ongoing research by Dr Zwacka, working with Dr Andrea Mohr and PhD students in their laboratory at the University’s School of Biological Sciences, into cancer therapy. They are now hoping to take the research forward to look at individual cancer samples and predict how they respond to treatment. In the future their findings could also help the development of drugs for cancer patients which can lead to a more effective treatment to kill cancer cells.