三阴乳腺癌(TNBC)目前尚无有效的靶向治疗方法。虽然大部分病人表皮生长因子受体(EGFR)高表达且通路异常激活，但临床实验显示TNBC对EGFR靶向药物耐受，而耐受机制尚不清楚。我们前期发现：CAP70可与EGFR结合，其表达在TNBC中下调，并与患者恶性程度相关；CAP70过表达可抑制EGFR通路激活并增强EGFR靶向药物对TNBC细胞增殖侵袭和EGFR活化的抑制作用。据此，我们推测：TNBC中CAP70下调，可解除其对EGFR通路的抑制，促进TNBC对EGFR靶向药物的耐受。本项目拟在分子、细胞、动物和临床层次开展研究，阐明CAP70下调导致TNBC细胞对EGFR靶向药物耐受的可能机制：CAP70通过与EGFR结合，调节其泛素化进而影响其降解，调节其二聚化进而影响其磷酸化。本研究将揭示TNBC对EGFR靶向药物耐受的分子机理，为CAP70联合EGFR靶向药物治疗TNBC提供理论依据。

Triple-negative breast cancer (TNBC) patients have the worst prognosis and distant metastasis-free survival among all major subtypes of breast cancer. The poor clinical outlook is further exacerbated by a lack of effective targeted therapies for TNBC. Epidermal growth factor receptor (EGFR) is a potential therapeutic target for TNBC, but clinical trials have shown that TNBC is resistant to EGFR-targeted drugs, and the mechanism of tolerance is unclear. In previous work, we found that CAP70 bound to EGFR, and CAP70 expression was down-regulated in TNBC tissues and was associated with malignancy in patients with TNBC. At the same time, CAP70 overexpression could enhance the inhibitory effect of EGFR-targeted drugs on TNBC cell proliferation, invasion and EGFR activation. Based on these preliminary results, we speculate that the down-regulation of CAP70 expression in TNBC relieves the inhibition of the EGFR pathway and promotes the tolerance of TNBC cells to EGFR-targeted drugs. This project intends to study the role and mechanism of CAP70 down-regulation leading to EGFR-targeted drug tolerance at the molecular, cellular, animal and clinical levels and the possibility of CAP70 as a new therapeutic strategy for TNBC. This study will elucidate the molecular mechanism of TNBC tolerance to EGFR-targeted drugs, identify and validate CAP70 as a new therapeutic target for TNBC to reverse the tolerance of TNBC cells to EGFR-targeted drugs, aiming to provide a new strategy for TNBC therapy.