肺癌脂肪酸代谢重编程的研究进展

doi:10.19401/j.cnki.1007-3639.2023.05.012

摘要/Abstract

摘要：

肺癌是最常见的恶性肿瘤，也是癌症死亡的主要原因。尽管靶向治疗和免疫治疗的发展显著改善了肺癌患者的疗效和预后，但总体5年生存率仍不到20%。因此，深入探索肺癌的发生、发展机制对于确立新的诊疗策略，进一步提高患者生存率具有重要的临床意义。代谢重编程是肿瘤维持恶性生物学行为的重要方式，既往研究表明，脂肪酸代谢重编程在肺癌的发生、发展过程中发挥重要作用，提示靶向肺癌脂肪酸代谢可能是新型抗肿瘤方案研发的重要方向。本文聚焦肺癌脂肪酸代谢重编程，拟从参与脂肪酸代谢包括摄取、合成、储存和分解等各环节的关键蛋白分子出发，综述脂肪酸代谢变化与肺癌发生、发展的关系，并对靶向脂肪酸代谢抗肿瘤治疗的应用现状及面临的挑战进行探讨，以期为确立新的肺癌治疗策略提供线索和参考。

关键词: 肺癌, 脂肪酸代谢, 重编程, 靶向治疗

Abstract:

Lung cancer is the most common malignant tumor and the leading cause of cancer-related mortality. Although the development of targeted therapy and immunotherapy has significantly improved the efficacy and prognosis of lung cancer patients, the overall 5-year survival rate is still lower than 20%. Therefore, in-depth exploration of the pathogenesis of lung cancer has important clinical significance for the development of new diagnosis and treatment strategies and further improvement of patient survival. Metabolic reprogramming is a crucial way for tumors to maintain malignant biological behavior. Previous studies have shown that fatty acid metabolism reprogramming has profound effects on tumorigenesis and progression of lung cancer, suggesting that targeting lung cancer fatty acid metabolism might be an important direction for the development of new anti-tumor regimens. This paper, focusing on the reprogramming of fatty acid metabolism, reviewed the relationship between fatty acid metabolism and lung cancer progression from the aspects of the key protein molecules involved in each procedure of fatty acid metabolism (including uptake, synthesis, storage and decomposition), and discussed the application status and challenges of anti-tumor therapy targeting fatty acid metabolism, expecting to provide clues and insights for the development of novel treatment regimen for lung cancer.

Key words: Lung cancer, Fatty acid metabolism, Reprogram, Targeted therapy

中图分类号:

R734.2

吴晶, 周娟, 苏春霞. 肺癌脂肪酸代谢重编程的研究进展[J]. 中国癌症杂志, 2023, 33(5): 517-526.

WU Jing, ZHOU Juan, SU Chunxia. Advances in fatty acid metabolism reprogramming of lung cancer[J]. China Oncology, 2023, 33(5): 517-526.

图/表 2

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Target	Agent	Mechanism of action	Drug development stage
ACC	ND-646	ACC inhibitor binding to the BC domain of ACC^[45]	Preclinical
FASN	Cerulenin	Non-competitive FASN inhibitor^[74]	Preclinical
FASN	Orlistat	Irreversible FASN inhibitor; Induction of ferroptosis in lung cancer cells^[70]	Preclinical
FASN	C75	Cytotoxicity; Side effects of anorexia and weight loss^[69]	Preclinical
FASN	TVB-3166	Reversible FASN inhibitor; Inhibition of β-catenin signaling and induction of apoptosis^[75]	Preclinical
FASN	TVB-2640	Reversible FASN inhibitor^[72,76]	Phase Ⅱ Clinical Trial (NCT03808558)
ACLY	SB-204990	Specific ACLY inhibitor; Inhibition of proliferation in lung tumor growth^[77]	Preclinical
SCD1	MF-438	Specific SCD1 inhibitor; Induction of apoptosis in lung adenocarcinoma stem cells^[80]	Preclinical