Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA; O'Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL, 35233, USA.
Mol Metab. 2024 May;83:101936. doi: 10.1016/j.molmet.2024.101936. Epub 2024 Apr 9.
Ceramides are sphingolipids that act as signaling molecules involved in regulating cellular processes including apoptosis, proliferation, and metabolism. Deregulation of ceramide metabolism contributes to cancer development and progression. Therefore, regulation of ceramide levels in cancer cells is being explored as a new approach for cancer therapy.
This review discusses the multiple roles of ceramides in cancer cells and strategies to modulate ceramide levels for cancer therapy. Ceramides attenuate cell survival signaling and metabolic pathways, while activating apoptotic mechanisms, making them tumor-suppressive. Approaches to increase ceramide levels in cancer cells include using synthetic analogs, inhibiting ceramide degradation, and activating ceramide synthesis. We also highlight combination therapies such as use of ceramide modulators with chemotherapies, immunotherapies, apoptosis inducers, and anti-angiogenics, which offer synergistic antitumor effects. Additionally, we also describe ongoing clinical trials evaluating ceramide nanoliposomes and analogs. Finally, we discuss the challenges of these therapeutic approaches including the complexity of ceramide metabolism, targeted delivery, cancer heterogeneity, resistance mechanisms, and long-term safety.
Ceramide-based therapy is a potentially promising approach for cancer therapy. However, overcoming hurdles in pharmacokinetics, specificity, and resistance is needed to optimize its efficacy and safety. This requires comprehensive preclinical/clinical studies into ceramide signaling, formulations, and combination therapies. Ceramide modulation offers opportunities for developing novel cancer treatments, but a deeper understanding of ceramide biology is vital to advance its clinical applications.
神经酰胺是一种鞘脂类物质，作为信号分子参与调控细胞凋亡、增殖和代谢等多种细胞过程。神经酰胺代谢失调与癌症的发生和发展密切相关。因此，调控癌细胞中的神经酰胺水平被视为一种新的癌症治疗方法。
本文综述了神经酰胺在癌细胞中的多种作用以及调控神经酰胺水平用于癌症治疗的策略。神经酰胺可抑制细胞存活信号和代谢途径，同时激活凋亡机制，从而发挥抑癌作用。增加癌细胞中神经酰胺水平的方法包括使用合成类似物、抑制神经酰胺降解以及激活神经酰胺合成。我们还强调了联合治疗策略，如使用神经酰胺调节剂与化疗、免疫疗法、凋亡诱导剂和抗血管生成剂联合应用，可产生协同的抗肿瘤效应。此外，我们还描述了正在评估神经酰胺纳米脂质体和类似物的临床试验。最后，我们讨论了这些治疗方法所面临的挑战，包括神经酰胺代谢的复杂性、靶向递送、癌症异质性、耐药机制和长期安全性。
基于神经酰胺的治疗方法可能是一种很有前途的癌症治疗方法。然而，要优化其疗效和安全性，需要克服药代动力学、特异性和耐药性等方面的挑战。这需要对神经酰胺信号、制剂和联合治疗进行全面的临床前/临床研究。神经酰胺的调节为开发新型癌症治疗方法提供了机会，但深入了解神经酰胺生物学对于推进其临床应用至关重要。
