PDF(Pubmed)
Abstract：
Eribulin (ERI), clinically utilized for locally advanced or metastatic breast tumors, has shown potential links to the immune system. Notably, the cGAS-STING pathway, a key component of innate immunity, has gained prominence. Yet, limited reports explore ERI\'s effects on the cGAS-STING pathway. Additionally, the nuclear presence of cGAS remains poorly understood. This study uniquely delves into ERI\'s impact on both the cytosolic cGAS-STING pathway and nuclear cGAS. ERI enhances nuclear localization of cGAS, resulting in hyper-activation of the cGAS-STING pathway in triple-negative breast cancer cells. Reduction of cGAS heightened both cell proliferation and ERI sensitivity. In clinical data using ERI in a neo-adjuvant setting, patients with low cGAS cases exhibited reduced likelihood of achieving pathological complete response after ERI treatment. These findings illuminate the potential of cGAS and IFNβ as predictive biomarkers for ERI sensitivity, providing valuable insights for personalized breast cancer treatment strategies.
摘要：
Eribulin(ERI),临床用于局部晚期或转移性乳腺肿瘤，已经显示出与免疫系统的潜在联系。值得注意的是,cGAS-STING途径，先天免疫的关键组成部分，已获得突出地位。然而，有限的报道探讨了ERI对cGAS-STING途径的影响。此外,cGAS的核存在仍然知之甚少。这项研究独特地探讨了ERI对胞质cGAS-STING途径和核cGAS的影响。ERI增强了cGAS的核定位，导致三阴性乳腺癌细胞中cGAS-STING途径的过度激活。cGAS的减少提高了细胞增殖和ERI敏感性。在新佐剂设置中使用ERI的临床数据中，低cGAS病例的患者在ERI治疗后获得病理完全缓解的可能性降低.这些发现阐明了cGAS和IFNβ作为ERI敏感性的预测生物标志物的潜力，为个性化乳腺癌治疗策略提供有价值的见解。
