In a study published in the journal Cell Reports Medicine, it was observed that the loss of the neurofibromin1 (NF1) gene leads to a reduced response to alpelisib. Researchers from the Department of Biomedicine at the University of Basel discovered that the dietary supplement N-acetylcysteine restored the sensitivity of cancer cells to alpelisib therapy.

The author of the study stated that, at present, patients with advanced and metastatic breast cancer lack effective treatment options. On the other hand, the PI3K signalling pathway is often overactive in breast cancer due to mutations that promote tumour development.

Hence, alpelisib therapy was found to be limited due to mutations. However, if the mutations are switched off, the resulting production of the NF1 protein makes the tumours resistant to treatment with alpelisib. It is known that NF1 suppresses the growth of tumours through a variety of signalling pathways. Several experiments have shown that the loss of NF1 can result in resistance in human cancer cells and tissue cultured from tumours.

Considering these modifications, the researchers tested the impacts of NF1 depletion using the well-known antioxidant N-acetylcysteine, which has a comparable impact on energy metabolism. This chemical is a popular nutritional supplement and a common component in cough syrups.

In the study, the researchers found that N-acetylcysteine had the opposite effect on resistance. They found that it restored the effectiveness of alpelisib in resistant cancer cells. The researchers noted that this reversal occurred via an additional intervention in another signalling pathway that also plays an important role in tumour growth. 

(Source: https://theprint.in/health/dietary-supplement-develops-resistance-in-breast-cancer-study/1512744/ )