Protein Found That Could Help Prevent Glioblastoma Recurrence

Glioblastoma brain cancer, CT scan

Researchers based at the Autonomous University of Barcelona (UAB) have uncovered a method that could stop tumor recurrence in individuals with the brain cancer glioblastoma.

The research team found a way to activate an important protein called DNA Fragmentation Factor 40 (DFF40) or Caspase-activated DNase (CAD), which is not active enough in glioblastoma cells. By enhancing its activity, they showed that more tumor cells went through a process called apoptosis and died off, which they hope could go some way to stopping recurrence in patients if proved in further studies.

“Promoting apoptosis to end properly in tumor cells could be a good therapeutic strategy to treat glioblastoma. The findings presented are promising and encourage us to carry out further research,” said Víctor Yuste, professor at the UAB and lead author of the paper published in the journal Cancers, in a press statement.

Glioblastoma is an aggressive brain cancer, representing 15% of all brain cancers, and is hard to treat. Less than 7% of patients survive longer than 5 years and even if treatment is initially successful, most cases recur.

Previous research has revealed that one likely reason recurrence is so common, is that glioblastoma cells do not have enough of the DFF40/CAD protein. This protein promotes cancer cell breakdown. The low activity of this protein in glioblastoma cells means that even if the cancer cells are damaged by treatment, they can still recover and continue spreading.

Using a glioblastoma cell line, Yuste and co-authors experimented by treating the cells with gossypol, a chemical extracted from cotton plants. They found that this substance, a natural terpenoid aldehyde, managed to increase DFF40/CAD activity in glioblastoma cells and push more cancer cells into apoptosis and cell death.

“We have seen that, contrary to other drugs, gossypol allows DFF40/CAD to stay in the nucleus for longer to promote its fragmentation. With our study, we demonstrated that compounds such as gossypol can push these cells to a point of no return after starting the cell death process without modifying them genetically,” said Laura Martinez-Escardó, a researcher at the UAB and first author of the paper about the study.

While this work is at a very early stage, the authors hope it might help create more effective therapies for this aggressive cancer in the future and perhaps help stop so many glioblastoma cases recurring.

“Unravelling that glioblastoma cells can enter into the point-of-no-return of apoptosis entails that those cells have no opportunity to acquire adaptive advantages. This finding is of special interest regarding the aggressiveness of glioblastoma and its refractory nature towards the current therapeutic strategies,” write the authors.

“Indeed, improving the efficacy of the compounds potentially employed to manage this illness, in terms of apoptosis induction, could be paramount to tackle its malignant progression.”

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