For all its persistence as an adversary, aggressive breast cancer carries a weakness of its own making. A University of Helsinki research group has been investigating where this weakness comes from and how it can be exploited.
The key lies in a protein called MYC, one of the most intriguing molecules in all of cancer research.
“Although MYC is overactive in over 70% of all cancers, it remains among the most challenging targets in drug development,” says Research Professor Juha Klefström of the University of Helsinki.
The difficulty is that the MYC protein is hard to tackle directly. Rather than targeting the protein itself, the researchers thus focused on how it affects the energy metabolism of cancer cells.
Cancer cells set their own trap
The research group found that in cells with high concentrations of the MYC protein, the mitochondria – the powerhouses of the cell – were working harder than usual.
Unlike healthy cells, which can switch energy source, cancer cells with strong MYC protein expression were locked into dependence on a single fuel: glutamine.
“We identified a metabolic vulnerability in aggressive breast cancer that provides a new target for treatment. By combining two investigational drugs, one inhibiting mitochondrial energy production and the other blocking glutamine utilization, we were able to significantly slow tumor growth in breast cancer tumor models,” says Researcher Johanna Anttila.
A step towards personalised treatment
Klefström stresses that while the findings mark a major leap forward in understanding the biology of MYC-driven cancers, they represent only a first step on the road to new treatments. The results are based on cell cultures and rodent experiments, and have not yet been extended to human patients.
The findings may lead to new and more personalised treatments. Since the activity of the MYC gene can be measured from a patient’s tumour sample, treatment would be offered not to all breast cancer patients, but only to those in whose tumours MYC is highly active.
“The next big step is to find not two drugs but a single drug capable of killing cancer cells that express the MYC protein. That would greatly simplify treatment. The first drug development projects aimed at this are already under way at the University of Helsinki,” says a hopeful Klefström.