Energy as a weak spot: a new approach to tackle aggressive breast cancer?
Could we stop cancer cells by cutting off their energy supply? That’s what Dione Blok, a bachelor’s student in Bio-Pharmaceutical Sciences, aimed to find out during her thesis research. She investigated a compound that affects the tumour cells’ energy metabolism. ‘Hopefully, these insights will provide new leads for treatments.’
Even when oxygen is plentiful, cancer cells in aggressive triple-negative breast cancer (TNBC) derive much of their energy from sugar breakdown (glycolysis). Using glycolysis enables them to grow rapidly—an adaptive trick for which cancer cells are notoriously known.
‘If we can block this energy source, the cancer cells face a real challenge,’ Dione explains. In her research, she focused on 2-deoxy-D-glucose (2-DG), a compound that disrupts energy production from glycolysis in cancer cells. But what happens to the cancer cells then?
Triple-negative breast cancer
Triple-negative breast cancer (TNBC) is an aggressive type of cancer that doesn’t grow due to hormones, making it more difficult to treat, because hormone therapy is not an option.
Blocking glycolysis proved effective: ‘We observed that cell growth decreased, and the cells often remained stuck in a certain phase of their division cycle,’ Dione explains. This could indicate that the cells struggle to continue dividing, thereby slowing tumour growth.
Different concentrations, different effects
As often happens in research, the results were surprising: 2-DG behaved differently at different concentrations. ‘At high concentrations, 2-DG inhibited the spread of cancer cells, while at lower concentrations, it slightly stimulated their movement.’ This suggests that the compound works differently depending on the concentration and highlights the complex interaction between energy metabolism and tumour aggressiveness.
In addition to effects on cell growth and migration, Dione also observed changes in how the cells organised their energy production. She noted alterations in the mitochondria—the cell’s ‘powerhouses.’ ‘This shows that cancer cells try to adapt when glycolysis is blocked,’ she says. This information could be crucial for developing new therapies targeting the tumour’s energy supply.
‘It was fascinating to see live how the cancer cells responded to the treatment’
Real-time cell cycle tracking
One of the most remarkable moments during her research was using FUCCI technology, which allowed Dione to monitor the cell cycle's progression. Each phase of the cell cycle is characterised by distinct proteins, and by linking these unique proteins to fluorescent markers, she could visualise the different phases in real-time. ‘It was fascinating to see live how the cancer cells responded to the treatment,’ she says.
Pursuing cancer research
Dione has now started a master’s programme in Bio-Pharmaceutical Sciences in Leiden, where she’s working on another research project focusing on triple-negative breast cancer. She would love to continue in cancer research, something she is made for, according to her supervisor Sylvia Le Dévédec. ‘I foresee a bright future for Dione in academia, as she has the perfect profile for conducting independent research during a PhD.’ Dione concludes: ‘I hope that my work will ultimately contribute to better treatments for patients who currently have limited options.’