新辅助化疗（NAC）常用于治疗局部晚期乳腺癌，但不幸的是，一部分肿瘤未能完全消除。凋亡和治疗诱导的细胞衰老（TIS）是两种细胞应激机制，但它们在介导NAC病理反应中的确切作用尚不明确。我们在两个乳腺癌基因数据集中调查了编码凋亡促进蛋白NOXA的基因PAMIP1在NAC后的表达变化，并在55个配对患者样本（NAC前后）中检查了NOXA蛋白在NAC中的表达变化。PAMIP1的表达在两个数据集中NAC后明显下降，并且我们的队列中75％的样本在NAC后下调了NOXA的表达。显示NAC后NOXA下降的配对样本基于Lamin-B1和Ki-67表达下调以及p16INK4a表达增加的标志进行TIS检查，大多数样本Lamin B1（66％）和Ki-67（80％）下降，p16INK4a增加（49％）。由于我们的队列包括未能获得完全病理反应的患者，这些发现对于TIS和NOXA下调在介导当前已建立的NAC对亚最佳反应中的作用具有临床意义。© 2023年 Springer Nature Limited。

Neoadjuvant chemotherapy (NAC) is a frequently utilized approach to treat locally advanced breast cancer, but, unfortunately, a subset of tumors fails to undergo complete pathological response. Apoptosis and therapy-induced senescence (TIS) are both cell stress mechanisms but their exact role in mediating the pathological response to NAC is not fully elucidated. We investigated the change in expression of PAMIP1, the gene encoding for the pro-apoptotic protein, NOXA, following NAC in two breast cancer gene datasets, and the change in NOXA protein expression in response to NAC in 55 matched patient samples (pre- and post-NAC). PAMIP1 expression significantly declined in post-NAC in the two sets, and in our cohort, 75% of the samples exhibited a downregulation in NOXA post-NAC. Matched samples that showed a decline in NOXA post-NAC were examined for TIS based on a signature of downregulated expression of Lamin-B1 and Ki-67 and increased p16INK4a, and the majority exhibited a decrease in Lamin B1 (66%) and Ki-67 (80%), and increased p16INK4a (49%). Since our cohort consisted of patients that did not develop complete pathological response, such findings have clinical implications on the role of TIS and NOXA downregulation in mediating suboptimal responses to the currently established NAC.© 2023. Springer Nature Limited.