Sarkar Abhisek, Banerjee Sounak, Biswas Kaushik
Department of Biological Sciences, Bose Institute, Kolkata, India.
Front Pharmacol. 2023 Nov 27;14:1282572. doi: 10.3389/fphar.2023.1282572. eCollection 2023.
Gangliosides are glycosphingolipids with prevalence in nervous tissue and their involvement in certain neuronal diseases have been widely known. Interestingly, many recent studies highlighted their importance in the development and progression of various cancers through orchestration of multiple attributes of tumorigenesis, i.e., promoting migration, invasion, escaping the host immune system, and influencing other cancer hallmarks. Therefore, the multidimensional role of gangliosides in different cancers has established them as potential cancer targets. However, the tremendous structural complexity and functional heterogeneity are the major challenges in ganglioside research. Moreover, despite numerous immunotherapeutic attempts to target different gangliosides, it has failed to yield consistent results in clinical trials owing to their poor immunogenicity, a broad range of cross-reactivity, severe side effects, lack of uniform expression as well as heterogeneity. The recent identification of selective O-acetylated ganglioside expression in cancer tissues, but not in normal tissues, has strengthened their potential as a better and specific target for treating cancer patients. It was further supported by reduced cross-reactivity and side effects in clinical trials, although poor immunogenicity remains a major concern. Therefore, in addition to characterization and identification of the biological importance of O-acetylated gangliosides, their specific and efficient targeting in cancer through engineered antibodies is an emerging area of glycobiology research. This review highlights the modulatory effect of select gangliosides on different hallmarks of cancer and presents the overall development of ganglioside targeted immunotherapies along with recent progress. Here, we have also discussed its potential for future modifications aimed towards improvement in ganglioside-based cancer therapies.
神经节苷脂是一类糖鞘脂，在神经组织中普遍存在，其与某些神经元疾病的关联已广为人知。有趣的是，最近许多研究强调了它们在各种癌症发生和发展过程中的重要性，通过协调肿瘤发生的多个特性，即促进迁移、侵袭、逃避宿主免疫系统以及影响其他癌症特征。因此，神经节苷脂在不同癌症中的多维作用使其成为潜在的癌症靶点。然而，巨大的结构复杂性和功能异质性是神经节苷脂研究中的主要挑战。此外，尽管针对不同神经节苷脂进行了大量免疫治疗尝试，但由于其免疫原性差、广泛的交叉反应性、严重的副作用、缺乏统一表达以及异质性，在临床试验中未能产生一致的结果。最近在癌组织而非正常组织中发现了选择性O - 乙酰化神经节苷脂的表达，这增强了它们作为治疗癌症患者更好且特异性靶点的潜力。尽管免疫原性差仍是一个主要问题，但临床试验中交叉反应性和副作用的降低进一步支持了这一点。因此，除了表征和鉴定O - 乙酰化神经节苷脂的生物学重要性外，通过工程抗体在癌症中对其进行特异性和高效靶向是糖生物学研究的一个新兴领域。本综述强调了特定神经节苷脂对癌症不同特征的调节作用，并介绍了神经节苷脂靶向免疫疗法的总体发展以及最新进展。在此，我们还讨论了其未来改进的潜力，旨在改善基于神经节苷脂的癌症治疗。
