Breast cancer (BC) is the most common
cancer with the highest frequency of death among women. BC is highly heterogenic at the genetic,
biological, and clinical level. Despite the significant improvements in diagnosis and treatments of BC, the high rate of
cancer recurrence and resistance to treatment remains a major challenge in clinical practice. This issue is particularly relevant in
Triple-Negative Breast Cancer (TNBC) subtype, for which
chemotherapy remains the main standard therapeutic approach. Here, we observed that BC cells, belonging to different subtypes, including the TNBC, display an increased expression of
Cockayne Syndrome group A (CSA)
protein, which is involved in multiple functions such as DNA repair, transcription, mitochondrial homeostasis, and cell division and that recently was found to confer cell robustness when it is up-regulated. We demonstrated that CSA ablation by
AntiSense Oligonucleotides (ASOs) drastically impairs tumorigenicity of BC cells by hampering their survival and proliferative capabilities without damaging normal cells. Moreover, suppression of CSA dramatically sensitizes BC cells to
platinum and
taxane derivatives, which are commonly used for BC first-line
therapy, even at very low doses not harmful to normal cells. Finally, CSA ablation restores
drug sensitivity in
oxaliplatin-resistant cells. Based on these results, we conclude that CSA might be a very attractive target for the development of more effective anticancer
therapies.