Zhang Yanyan, Yang Zhichao, Liu Yuchen, Pei Jinjin, Li Ruojie, Yang Yanhui
Qinba State Key Laboratory of Biological Resources and Ecological Environment, Shaanxi Province Key Laboratory of Bio-Resources, College of Bioscience and Bioengineering, Bashan Mountains Bioresources Comprehensive Development C.I.C, Shaanxi University of Technology, Qinling, Hanzhong, 723001, China.
Department of Epidemiology and Health Statistics, School of Public Health, Dalian Medical University, Dalian, China.
Lipids Health Dis. 2025 Jan 13;24(1):12. doi: 10.1186/s12944-024-02426-0.
Lipid metabolism in cancer is characterized by dysregulated lipid regulation and utilization, critical for promoting tumor growth, survival, and resistance to therapy. Pancreatic cancer (PC) is a highly aggressive malignancy of the gastrointestinal tract that has a dismal 5-year survival rate of less than 10%. Given the essential function of the pancreas in digestion, cancer progression severely disrupts its function. Standard treatments for PC such as surgical resection, chemotherapy, and radiotherapy. However, these therapies often face significant challenges, including biochemical recurrence and drug resistance.Given these limitations, new therapeutic approaches are being developed to target tumor metabolism. Dysregulation of cholesterol biosynthesis and alterations in fatty acids (FAs), such as palmitate, stearate, omega-3, and omega-6, have been observed in pancreatic cancer. These lipids serve as energy sources, signaling molecules, and essential components of cell membranes. Their accumulation fosters an immunosuppressive tumor microenvironment that supports cancer cell proliferation and metastasis.Moreover, lipid metabolism dysregulation within immune cells, particularly T cells, impairs immune surveillance and weakens the body's defenses against cancer. Abnormal lipid metabolism also contributes to drug resistance in PC. Despite these challenges, targeting lipid metabolism may offer a promising therapeutic strategy. By enhancing lipid peroxidation, the induction of ferroptosis-a form of regulated cell death-could impair the survival of PC cells and hinder disease progression.
癌症中的脂质代谢以脂质调节和利用失调为特征，这对促进肿瘤生长、存活及抗治疗能力至关重要。胰腺癌（PC）是胃肠道的一种高度侵袭性恶性肿瘤，其5年生存率极低，不到10%。鉴于胰腺在消化中的重要功能，癌症进展会严重破坏其功能。PC的标准治疗方法包括手术切除、化疗和放疗。然而，这些疗法常常面临重大挑战，包括生化复发和耐药性。鉴于这些局限性，正在开发针对肿瘤代谢的新治疗方法。在胰腺癌中已观察到胆固醇生物合成失调以及脂肪酸（FAs）的改变，如棕榈酸、硬脂酸、ω-3和ω-6。这些脂质可作为能量来源、信号分子及细胞膜的重要组成部分。它们的积累促进了免疫抑制性肿瘤微环境的形成，支持癌细胞增殖和转移。此外，免疫细胞尤其是T细胞内的脂质代谢失调会损害免疫监视并削弱机体对癌症的防御能力。异常的脂质代谢也导致了PC的耐药性。尽管存在这些挑战，但靶向脂质代谢可能提供一种有前景的治疗策略。通过增强脂质过氧化作用，诱导铁死亡（一种程序性细胞死亡形式）可能会损害PC细胞的存活并阻碍疾病进展。
