In recent years, cancer therapies have often fallen short of expectations, with tumors developing resistance to medication. One such example is alpelisib, a drug approved for use in Switzerland as a treatment for advanced breast cancer.
However, a research group at the Department of Biomedicine of the University of Basel has made a breakthrough in understanding the reasons behind this resistance, publishing their findings in the journal Cell Reports Medicine.
For patients suffering from advanced and metastatic breast cancer, effective treatment options are limited. The PI3K signaling pathway is frequently overactive in breast cancer due to mutations that encourage tumor growth.
The approval of the PI3K inhibitor alpelisib was thus eagerly awaited. However, Professor Mohamed Bentires-Alj, the head of the research group, points out that “the success of the medication is severely limited by resistance.”
Bentires-Alj’s team set out to identify the genetic basis of resistance by determining which genes had mutated to make cancer cells resistant. They discovered that mutations that halted the production of the NF1 protein rendered tumors resistant to alpelisib treatment.
While NF1 is known to suppress tumor growth through various signaling pathways, its connection to alpelisib resistance was previously unknown.
Further experiments confirmed that the loss of NF1 resulted in resistance in human cancer cells and in tissue cultured from tumors. Bentires-Alj explains that “the absence of NF1 is the elephant in the room; it throws everything into disarray within the cell and hinders successful treatment.”
Lead author of the study, Dr. Priska Auf der Maur, notes that the loss of NF1 impacts the cell’s energy reserves. “They stop producing as much energy using mitochondria; instead, they switch to other energy production pathways,” she says.
Based on these observations, the researchers conducted experiments with the antioxidant N-acetylcysteine, a common dietary supplement and cough medicine ingredient, which has similar effects on energy metabolism and was expected to mimic the effects of NF1 loss.
Contrary to expectations, N-acetylcysteine restored and even enhanced the effectiveness of alpelisib in resistant cancer cells. Further analysis revealed that this occurred through intervention in another signaling pathway that also plays a crucial role in tumor growth.
The loss of NF1 is also implicated in resistance to other medications, suggesting that combination therapy with N-acetylcysteine could be a viable option in these cases as well.
Bentires-Alj emphasizes the significance of these findings for clinical research, stating that “as N-acetylcysteine is a safe and widespread additive, this result is highly relevant.”
He believes that a combination of N-acetylcysteine and alpelisib could potentially improve the treatment of advanced breast cancer. The next step, he suggests, would be to conduct clinical studies with breast cancer patients to confirm the positive effects observed in the laboratory.
N-acetylcysteine (NAC) is an antioxidant and a derivative of the naturally occurring amino acid L-cysteine. It has a variety of health benefits and is commonly used as a dietary supplement.
NAC plays a crucial role in the body’s production of glutathione, a powerful antioxidant that helps protect cells against oxidative stress and damage caused by reactive oxygen species (ROS).
In addition to its antioxidant properties, NAC has mucolytic effects, meaning it can break down mucus in the airways, making it an effective ingredient in many cough medicines. It has also been used to treat a range of conditions, such as chronic obstructive pulmonary disease (COPD), asthma, and cystic fibrosis, as well as to prevent kidney damage from certain drugs or to treat acetaminophen (paracetamol) overdose.
Yes, N-acetylcysteine (NAC) is available to the public as an over-the-counter dietary supplement and as an ingredient in various cough medicines. It can be purchased without a prescription in many countries, including the U.S., and can be found in most health food stores.
NAC is available in various forms, including capsules, tablets, and powder, and is typically marketed for its antioxidant and respiratory health benefits.
However, it is essential to note that the research mentioned in the previous response is still in the early stages, and the potential use of NAC in cancer treatment is not yet well-established. The next step would be to conduct clinical trials with cancer patients to confirm the positive effects observed in the laboratory setting.
Before considering NAC supplementation or using it for any specific health condition, it is always a good idea to consult a healthcare professional to discuss the appropriate dosage, potential side effects, and any possible interactions with other medications or supplements you may be taking.
N-acetylcysteine (NAC) is generally considered safe when used appropriately. However, like any supplement or medication, it can cause side effects in some individuals. These side effects are usually mild and not as serious as pharmaceutical medication, and may include:
Keep in mind that the severity and frequency of side effects may vary depending on the individual, dosage, and method of administration. It is essential to consult with a healthcare professional before starting NAC supplementation to discuss the appropriate dosage, potential side effects, and any possible interactions with other medications or supplements you may be taking.
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