China Oncology ›› 2023, Vol. 33 ›› Issue (5): 517-526.doi: 10.19401/j.cnki.1007-3639.2023.05.012
• Review • Previous Articles Next Articles
WU Jing(), ZHOU Juan, SU Chunxia()
Received:
2022-06-21
Revised:
2022-09-05
Online:
2023-05-30
Published:
2023-06-16
Contact:
SU Chunxia
CLC Number:
WU Jing, ZHOU Juan, SU Chunxia. Advances in fatty acid metabolism reprogramming of lung cancer[J]. China Oncology, 2023, 33(5): 517-526.
Fig. 1
Fatty acid metabolism in lung cancer Lung cancer cells obtain fatty acids from exogenous uptake and de novo lipogenesis. Exogenous uptake of fatty acids from the microenvironment is facilitated by CD36, FATP and FABP. De novo fatty acid synthesis mainly refers to the generation of palmitate from citrate under the enzymatic activities of ACLY, ACC and FASN enzymes, and then can be desaturated and elongated to form diverse lipidomic species. SREBP1 regulates fatty acid synthesis by regulating the expression of fatty acid synthesis-related enzymes at the transcriptional level. When nutrients are sufficient, fatty acids are stored as lipid droplets.And when energy is stressed, these fatty acids are released from lipid dropletsthrough lipolysis, and energy is generated through fatty acid oxidation. In addition to providing energy, free fatty acids, as important signaling molecules, participate in intracellular signaling through FFAR, thereby affecting various physiological processes of cells. FFAR: Free fatty acid receptor; ACLY: ATP-citrate lyase; ACC: Acetyl-CoA carboxylase; FASN: Fatty acid synthase; SCD1: Stearyl coenzyme A desaturated enzyme 1; ATGL: Adipose triglyceride lipase; HSL: Hormone-sensitive lipase; MAGL: Monoacylglycerol lipase; ACSL: Long-chain acyl-CoA synthetase; CPT1: Carnitine palmitoyl transferase; EGFR: Epidermal growth factor receptor; AMPK: AMP-activated protein kinase; SREBP1: Sterol regulatory element-binding proteins; SRE: Sterol regulatory element."
Tab. 1
Inhibitors targeting fatty acid synthesis-related enzymes in lung cancer"
Target | Agent | Mechanism of action | Drug development stage |
---|---|---|---|
ACC | ND-646 | ACC inhibitor binding to the BC domain of ACC[ | Preclinical |
FASN | Cerulenin | Non-competitive FASN inhibitor[ | Preclinical |
FASN | Orlistat | Irreversible FASN inhibitor; Induction of ferroptosis in lung cancer cells[ | Preclinical |
FASN | C75 | Cytotoxicity; Side effects of anorexia and weight loss[ | Preclinical |
FASN | TVB-3166 | Reversible FASN inhibitor; Inhibition of β-catenin signaling and induction of apoptosis[ | Preclinical |
FASN | TVB-2640 | Reversible FASN inhibitor[ | Phase Ⅱ Clinical Trial (NCT03808558) |
ACLY | SB-204990 | Specific ACLY inhibitor; Inhibition of proliferation in lung tumor growth[ | Preclinical |
SCD1 | MF-438 | Specific SCD1 inhibitor; Induction of apoptosis in lung adenocarcinoma stem cells[ | Preclinical |
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