N-acetylcysteine (NAC) is a widely used
antioxidant with therapeutic potential. However, the
cancer-promoting effect of NAC observed in some preclinical studies has raised concerns regarding its clinical use.
Reactive oxygen species (ROS) can mediate signaling that results in both
cancer-promoting and
cancer-suppressing effects. The beneficial effect of NAC may depend on whether the type of
cancer relies on ROS signaling for its survival and
metastasis.
Triple-negative breast cancer (TNBC) has aggressive phenotypes and is currently treated with standard
chemotherapy as the main systemic treatment option. Particularly, basal-like TNBC cells characterized by inactivated BRCA1 and mutated TP53 produce high ROS levels and rely on ROS signaling for their survival and malignant progression. In addition, the high ROS levels in TNBC cells can mediate the interplay between
cancer cells and the tissue microenvironment (TME) to trigger the recruitment and conversion of stromal cells and induce hypoxic responses, thus leading to the creation of
cancer-supportive TMEs and increased
cancer aggressiveness. However, NAC treatment effectively reduces the ROS production and ROS-mediated signaling that contribute to cell survival,
metastasis, and drug resistance in TNBC cells. Therefore, the inclusion of NAC in standard
chemotherapy could probably provide additional benefits for TNBC patients.