Molecular Targeting Unit, Department of Research, Fondazione IRCCS Istituto Nazionale dei Tumori di Milano, Via Amadeo 42, 20133 Milan, Italy.
Int J Mol Sci. 2020 Nov 28;21(23):9069. doi: 10.3390/ijms21239069.
Breast cancer (BC) is the most common tumour in women. Although the introduction of novel therapeutic approaches in clinical practice has dramatically improved the clinical outcome of BC patients, this malignant disease remains the second leading cause of cancer-related death worldwide. The wingless/integrated (Wnt) signalling pathway represents a crucial molecular node relevantly implicated in the regulation of normal somatic stem cells as well as cancer stem cell (CSC) traits and the epithelial-mesenchymal transition cell program. Accordingly, Wnt signalling is heavily dysregulated in BC, and the altered expression of different Wnt genes is significantly associated with cancer-related aggressive behaviours. For all these reasons, Wnt signalling represents a promising therapeutic target currently under clinical investigation to achieve cancer eradication by eliminating CSCs, considered by most to be responsible for tumour initiation, relapse, and drug resistance. In this review, we summarized the current knowledge on the Wnt signalling pathway in BC and have presented evidence implicating the suitability of Wnt targeting in an attempt to improve the outcome of patients without affecting the normal somatic stem cell population.
乳腺癌（BC）是女性最常见的肿瘤。虽然在临床实践中引入新的治疗方法极大地改善了 BC 患者的临床预后，但这种恶性疾病仍然是全球癌症相关死亡的第二大主要原因。无翅型/整合素（Wnt）信号通路是一个关键的分子节点，与正常体干细胞以及癌症干细胞（CSC）特征和上皮-间充质转化细胞程序的调控密切相关。因此，Wnt 信号在 BC 中严重失调，不同 Wnt 基因的表达改变与癌症相关的侵袭性行为显著相关。基于所有这些原因，Wnt 信号被认为是目前临床研究中通过消除 CSCs 来实现癌症根除的一个很有前途的治疗靶点，CSCs 被认为是肿瘤起始、复发和耐药的主要原因。在这篇综述中，我们总结了 Wnt 信号通路在 BC 中的最新知识，并提出了证据表明靶向 Wnt 是合适的，试图改善患者的预后而不影响正常的体干细胞群体。
