The London Breast Institute, Princess Grace Hospital, London, U.K.
Cancer Genomics Proteomics. 2024 Nov-Dec;21(6):549-556. doi: 10.21873/cgp.20471.
Expression of disialoganglioside GD2 in normal tissues is primarily limited to the central nervous system, peripheral sensory nerve fibers, dermal melanocytes, lymphocytes, and mesenchymal stem cells. Its widespread overexpression in various cancer types allows it to be classified as a tumor-associated antigen with potential diagnostic and therapeutic implications. This article reviews the synthesis pathways of GD2 and its role in cancer cell adhesion, proliferation, and metastasis with a focus on breast cancer. GD2 appears to be overexpressed on the outer membrane of most breast cancer cells and breast cancer stem cells (BCSCs) and is closely linked to epithelial-mesenchymal transition (EMT). GD3 synthase (GD3S) is considered to be the rate-determining step in GD2 synthesis. Clinical studies indicate that GD2 expression is increased in 35-70% of breast cancer samples, with higher levels in triple-negative breast cancer (TNBC). This overexpression correlates with more aggressive tumor features and worse prognosis. Therapeutic targeting of GD2 with monoclonal antibodies (moABs) like dinutuximab and naxitamab has demonstrated anti-cancer activity in preclinical cancer models and human clinical trials against high-risk neuroblastoma reducing tumor growth and enhancing survival. GD2-specific chimeric antigen receptor (CAR) T-cell therapy and GD3S inhibition present other promising therapeutic strategies to improve clinical outcomes. Furthermore, GD2-targeted vaccines are currently being investigated in cancer therapy. This narrative review article underscores the critical role of GD2 in breast cancer pathogenesis and highlights the promising therapeutic opportunities it offers. It advocates for the initiation of clinical trials to further explore the potential of GD2-targeted treatment in combination with standard breast cancer therapies.
二唾液酸神经节苷脂 GD2 在正常组织中的表达主要局限于中枢神经系统、外周感觉神经纤维、皮肤黑素细胞、淋巴细胞和间充质干细胞。其在各种癌症类型中的广泛过表达使其被归类为具有潜在诊断和治疗意义的肿瘤相关抗原。本文综述了 GD2 的合成途径及其在癌细胞黏附、增殖和转移中的作用，重点关注乳腺癌。GD2 似乎在外膜上过表达于大多数乳腺癌细胞和乳腺癌干细胞（BCSCs），并且与上皮-间充质转化（EMT）密切相关。GD3 合酶（GD3S）被认为是 GD2 合成的限速步骤。临床研究表明，GD2 在 35-70%的乳腺癌样本中表达增加，在三阴性乳腺癌（TNBC）中表达更高。这种过表达与更具侵袭性的肿瘤特征和更差的预后相关。用单克隆抗体（moABs）如 dinutuximab 和 naxitamab 靶向 GD2 的治疗已在临床前癌症模型和针对高危神经母细胞瘤的人类临床试验中证明了抗癌症活性，降低了肿瘤生长并提高了生存率。GD2 特异性嵌合抗原受体（CAR）T 细胞疗法和 GD3S 抑制为改善临床结果提供了其他有前途的治疗策略。此外，目前正在癌症治疗中研究 GD2 靶向疫苗。本综述文章强调了 GD2 在乳腺癌发病机制中的关键作用，并强调了它提供的有前途的治疗机会。它主张启动临床试验，以进一步探索 GD2 靶向治疗与标准乳腺癌治疗联合的潜在应用。
