BASEL, Switzerland — Many cancer therapies out there, unfortunately, don’t produce the desired results patients are counting on, especially in the late stages. In advanced breast cancer, this happens because the cancer cells become resistant to the treatments. Now, researchers from the University of Basel have revealed a mechanism behind this and one possible solution: combination therapy with a popular dietary supplement, N-acetylcysteine.
“Unfortunately, it turned out that the success of the medication is severely limited by resistance,” says Professor Mohamed Bentires-Alj, head of the research group, in a university release. “Hence, we urgently need to find out more about how resistance arises.”
To do this, his team set out to find the genes responsible for making cancerous cells resistant. They found that mutations which switch off the production of NF1 protein, which plays a crucial role in tumor suppression, made the tumors resistant to treatment with alpelisib, a common drug for these patients. This is the first time scientists have discovered a link between genetic expression of NF1 and resistance to this specific drug. The group repeated experiments to validate this, and everything lined up consistently.
“So the absence of NF1 is the elephant in the room; it throws everything into disarray within the cell and hinders successful treatment,” says Bentires-Alj.
The team also found that when NF1 loses its function, it impacts the cell’s energy reserves.
“They stop producing as much energy using mitochondria; instead, they switch to other energy production pathways,” explains the lead author of the study, Dr. Priska Auf der Maur.
This is where the antioxidant N-acetylcysteine comes in
NAC is a popular dietary supplement which is often an ingredient in several cough medicines. The researchers used this supplement to mimic the effects of NF1 loss. To their surprise, NAC was able to make the cells respond to alpelisib again, even increasing their responsiveness. The mechanism for this involves it acting on another signaling pathway implicated in tumor growth, according to their analysis. Combining conventional treatment with NAC could be a game-changer.
“As N-acetylcysteine is a safe and widespread additive, this result is highly relevant for clinical research,” says Bentires-Alj.
The researcher believes that not all hope is lost, and that combining these therapies could improve outcomes for those with late-stage breast cancer. Now, the team is looking ahead to testing these effects outside of the lab. They hope to run clinical trials with breast cancer patients before considering widespread use in clinical settings.
The findings are published in the journal Cell Reports Medicine.