乳腺癌是严重威胁女性身心健康的常见肿瘤之一。F-box和WD重复结构域含7（FBXW7）是一种肿瘤抑制蛋白。作为泛素连接酶底物识别元件，FBXW7参与泛素蛋白酶体系，并通常负责关键致癌蛋白的泛素化和降解，进一步在细胞分化、凋亡和代谢过程中发挥重要作用。FBXW7水平降低会导致相关底物稳定性异常，已有报道表明FBXW7基因突变和/或缺失与乳腺癌恶性发展和化疗抗性相关。鉴于乳腺癌临床药物抵抗难题缺乏有效解决方法，阐明FBXW7的作用机制可以为靶向药物的探索提供理论依据。因此，在本综述中，我们将重点关注FBXW7在一系列乳腺癌恶性行为中的作用，并总结与之相关的细胞靶标、信号通路以及调控FBXW7表达的机制。我们还提出了针对FBXW7的治疗策略，探讨替代疗法和特异性肿瘤标志物在乳腺癌治疗中的应用前景。© 2023. 意大利国家癌症研究所“Regina Elena”。

Breast cancer is one of the frequent tumors that seriously endanger the physical and mental well-being in women. F-box and WD repeat domain-containing 7 (FBXW7) is a neoplastic repressor. Serving as a substrate recognition element for ubiquitin ligase, FBXW7 participates in the ubiquitin-proteasome system and is typically in charge of the ubiquitination and destruction of crucial oncogenic proteins, further performing a paramount role in cell differentiation, apoptosis and metabolic processes. Low levels of FBXW7 cause abnormal stability of pertinent substrates, mutations and/or deletions in the FBXW7 gene have been reported to correlate with breast cancer malignant progression and chemoresistance. Given the lack of an effective solution to breast cancer's clinical drug resistance dilemma, elucidating FBXW7's mechanism of action could provide a theoretical basis for targeted drug exploration. Therefore, in this review, we focused on FBXW7's role in a range of breast cancer malignant behaviors and summarized the pertinent cellular targets, signaling pathways, as well as the mechanisms regulating FBXW7 expression. We also proposed novel perspectives for the exploitation of alternative therapies and specific tumor markers for breast cancer by therapeutic strategies aiming at FBXW7.© 2023. Italian National Cancer Institute ‘Regina Elena’.