One of the challenges facing specialists treating breast cancer is that cancer cells become resistant to treatment. This occurs, for example, with alpelisib, a drug used in the treatment of advanced breast cancer. Now, scientists from the Department of Biomedicine at the University of Basel have discovered why these tumors develop resistance to this therapy and a possible way to avoid it thanks to an antioxidant that is often used as a dietary supplement and as an ingredient in expectorant medications (to reduce the thickness of the mucus and facilitate its extraction).
These researchers have found that loss of the neurofibromin 1 (NF1) gene reduces the response to this drug and that by combining alpelisib with the dietary supplement N-acetylcysteine, cancer cells became receptive to treatment. The results of the study have been published in Cell Reports Medicine.
There are currently no effective therapeutic options available for patients with advanced breast cancer, especially if metastases are developing, and therefore great expectations were generated with the approval of alpelisib, whose function is to inhibit the PI3K signaling pathway, which is usually hyperactivated by mutations in breast cancer and contributes to tumor formation.
N-acetylcysteine restored and even potentiated the effects of alpelisib on treatment-resistant breast cancer cells
However, the effectiveness of this active principle is significantly limited by the resistance of malignant cells, highlighted Dr. Mohamed Bentires-Alj, head of the research group, whose objective was to identify the genes whose alteration makes cancer cells resistant. What they found is that the mutations that turned off the NF1 protein made the tumors resistant to treatment. NF1 is known to suppress tumor growth through several signaling pathways, but the gene has not yet been linked to alpelisib resistance.
N-acetylcysteine, a dietary supplement against breast cancer
An analysis revealed that the loss of NF1 influences the energy balance of the cell: “Not as much energy is produced anymore with the help of mitochondria, but instead switches to other forms of energy production,” explained Dr. Priska. in Maur, first author of the study. These changes prompted the researchers to carry out experiments with the antioxidant N-acetylcysteine, which has a similar effect on energy metabolism and was intended to mimic the effects of NF1 loss.
To the surprise of these scientists, N-acetylcysteine had the opposite effect: it restored and even potentiated the effects of alpelisib on resistant cancer cells. This is done through additional intervention in another signaling pathway, which also plays an important role in tumor growth, as they discovered through further analysis. Interestingly, the loss of NF1 is also implicated in resistance to other drugs, so it is possible that it could be combated with combination therapy with N-acetylcysteine.
“Since N-acetylcysteine is a widely used and safe additive, this result is highly relevant for clinical research,” concludes Bentires-Alj, who is of the opinion that combining N-acetylcysteine with alpelisib could improve the treatment of advanced breast cancer. Now it is necessary to confirm the positive effects that have been observed in the laboratory in clinical trials with patients with breast cancer.
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