PDF(Pubmed)
Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
CONCLUSIONS: 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.
摘要：
背景：神经酰胺是神经鞘脂，作为信号分子参与调节细胞过程，包括细胞凋亡，扩散,和新陈代谢。神经酰胺代谢的失调有助于癌症的发展和进展。因此,作为癌症治疗的新方法，正在探索调节癌细胞中的神经酰胺水平。
目的：本文讨论了神经酰胺在癌细胞中的多种作用以及调节神经酰胺水平用于癌症治疗的策略。神经酰胺减弱细胞存活信号和代谢途径，在激活凋亡机制的同时，让它们抑制肿瘤。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，和激活神经酰胺合成。我们还强调联合治疗，如使用神经酰胺调节剂与化疗，免疫疗法，凋亡诱导剂，和抗血管生成药物，提供协同抗肿瘤作用。此外,我们还描述了正在进行的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的挑战，包括神经酰胺代谢的复杂性，有针对性的交付，癌症异质性，抵抗机制，和长期安全。
结论：基于神经酰胺的治疗是一种潜在的癌症治疗方法。然而,克服药代动力学的障碍，特异性，并且需要抗性来优化其功效和安全性。这需要对神经酰胺信号进行全面的临床前/临床研究，配方，和组合疗法。神经酰胺调制为开发新的癌症治疗提供了机会，但更深入地了解神经酰胺生物学对推进其临床应用至关重要。
目的：本文讨论了神经酰胺在癌细胞中的多种作用以及调节神经酰胺水平用于癌症治疗的策略。神经酰胺减弱细胞存活信号和代谢途径，在激活凋亡机制的同时，让它们抑制肿瘤。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，和激活神经酰胺合成。我们还强调联合治疗，如使用神经酰胺调节剂与化疗，免疫疗法，凋亡诱导剂，和抗血管生成药物，提供协同抗肿瘤作用。此外,我们还描述了正在进行的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的挑战，包括神经酰胺代谢的复杂性，有针对性的交付，癌症异质性，抵抗机制，和长期安全。
结论：基于神经酰胺的治疗是一种潜在的癌症治疗方法。然而,克服药代动力学的障碍，特异性，并且需要抗性来优化其功效和安全性。这需要对神经酰胺信号进行全面的临床前/临床研究，配方，和组合疗法。神经酰胺调制为开发新的癌症治疗提供了机会，但更深入地了解神经酰胺生物学对推进其临床应用至关重要。
