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Ganglioside GD2: a novel therapeutic target in triple-negative breast cancer
Annals of the New York Academy of Sciences ( IF 4.1 ) Pub Date : 2021-10-01 , DOI: 10.1111/nyas.14700
Claire Shao 1 , Vivek Anand 1 , Michael Andreeff 1 , Venkata Lokesh Battula 1, 2
Affiliation  

Triple-negative breast cancer (TNBC) is a heterogeneous disease characterized by lack of hormone receptor expression and is known for high rates of recurrence, distant metastases, and poor clinical outcomes. TNBC cells lack targetable receptors; hence, there is an urgent need for targetable markers for the disease. Breast cancer stem-like cells (BCSCs) are a fraction of cells in primary tumors that are associated with tumorigenesis, metastasis, and resistance to chemotherapy. Targeting BCSCs is thus an effective strategy for preventing cancer metastatic spread and sensitizing tumors to chemotherapy. The CD44hiCD24lo phenotype is a well-established phenotype for identification of BCSCs, but CD44 and CD24 are not targetable markers owing to their expression in normal tissues. The ganglioside GD2 has been shown to be upregulated in primary TNBC tumors compared with normal breast tissue and has been shown to identify BCSCs. In this review, we discuss GD2 as a BCSC- and tumor-specific marker in TNBC; epithelial-to-mesenchymal transition and the signaling pathways that are upstream and downstream of GD2 and the role of these pathways in tumorigenesis and metastasis in TNBC; direct and indirect approaches for targeting GD2; and ongoing clinical trials and treatments directed against GD2 as well as future directions for these strategies.

中文翻译:

神经节苷脂GD2:三阴性乳腺癌的新治疗靶点

三阴性乳腺癌 (TNBC) 是一种异质性疾病,其特征是缺乏激素受体表达,并以高复发率、远处转移和不良临床结果而闻名。TNBC 细胞缺乏可靶向的受体;因此,迫切需要针对该疾病的靶向标志物。乳腺癌干细胞样细胞 (BCSCs) 是原发性肿瘤中与肿瘤发生、转移和化疗耐药相关的一小部分细胞。因此,靶向 BCSCs 是预防癌症转移扩散和使肿瘤对化疗敏感的有效策略。CD44 hi CD24 lo表型是用于鉴定 BCSCs 的公认表型,但 CD44 和 CD24 由于它们在正常组织中的表达而不是可靶向的标记物。与正常乳腺组织相比,已显示神经节苷脂 GD2 在原发性 TNBC 肿瘤中上调,并已显示可识别 BCSC。在这篇综述中,我们讨论了 GD2 作为 TNBC 中的 BCSC 和肿瘤特异性标志物。上皮间质转化和 GD2 上游和下游的信号通路以及这些通路在 TNBC 肿瘤发生和转移中的作用;针对 GD2 的直接和间接方法;和正在进行的针对 GD2 的临床试验和治疗以及这些策略的未来方向。
更新日期:2021-10-01
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