The Lipid Metabolic Landscape of Cancers and New Therapeutic Perspectives

Abstract

Lipid metabolism reprograming, as a hallmark of malignancy, has received renewed interest in recent years in such areas as energy sources, cell membrane components, and signaling molecules involved in the rapid tumor growth and the adaptation to the tumor microenvironment. Lipid metabolism deregulation in cancer involves multiple aspects, including an increased lipid uptake, endogenous de novo fatty acid synthesis, fatty acid oxidation, and cholesterol accumulation, thereby promoting tumor growth and progression. Recent advances in the understanding of specific metabolic alterations in cancer reveal novel pathogenesis mechanisms and a growing number of drugs targeting lipid metabolism have been applied in anti-tumor therapy. Thus, this review discusses the lipid metabolic landscape of cancers and the interplay with oncogenic signaling, and summarizes potential therapeutic targets to improve the therapeutic efficiency in cancer patients, in order to provide more reference and thinking for the treatment of lipid metabolism of cancer patients.

Metabolic Classification and Intervention Opportunities for Tumor Energy Dysfunction

“…Breast adenocarcinoma [21] Leukemia [21] Multiple myeloma [21] Prostate adenocarcinoma [21] Ovarian adenocarcinoma [21] Gastric adenocarcinoma [22] Pancreatic adenocarcinoma [22] Small cell lung cancer [22] Squamous cell carcinoma [22] 3-Bromopyruvate [21] CD36 inhibitors [22] Fatty acid synthesis FASN [25,26] SREBP1 [27,28] LXR [29] SCD-1 [29] Breast adenocarcinoma [25] Colon adenocarcinoma [28,30] Pancreatic adenocarcinoma [26,31] Ovarian carcinoma [28] Prostate adenocarcinoma [27] TVB-3136 [25] TVB-2640 [25] IPI-9119 [27] Cerulenin [28] Orlistat [28,32,33] C93 [28] Proton pump inhibitors [26,34] Fatty acid oxidation CPT1 [35] IDH2 [36] Glioblastoma [36] Acute myeloid leukemia [35] Etomoxir [35,36] Prostaglandin E2…”

“…Cancer-associated adipose tissue Extracellular lipid uptake Tumor [21][22][23]: CD36 increase FABP4 increase LPL increase Adipocyte [21,24]:…”

Anthracyclins Increase PUFAs: Potential Implications in ER Stress and Cell Death

“…Among others, the malignant transformation of hepatocytes dysregulates the de novo lipogenesis [ 5 ]. This altered lipid metabolism is involved in rapid tumor growth and adaptation to the tumor microenvironment [ 6 ].…”

Synthesis and biological evaluation of 4-phenoxy-phenyl isoxazoles as novel acetyl-CoA carboxylase inhibitors

“…Therefore, elevated FASyn is accepted as a major characteristic of numerous cancers, including those in the prostate, colon, breast, lung, and liver. The drugs that intervene with the enzymes in FASyn may provide an innovative approach for the fight against cancer [5][6][7][8] .…”

“…118.5-119.5 C 1. H NMR (400 MHz, CDCl 3 ): d 7.71 (t, J ¼ 8.2 Hz, 2H),6.99 (t, J ¼ 7.7 Hz, 4H),6.91 (d, J ¼ 8.8 Hz, 2H), 6.40 (s, 1H), 5.95 (d, J ¼ 9.3 Hz, 1H), 5.47-5.28 (m, 1H), 3.92 (t, J ¼ 4.5 Hz, 2H), 2.04 (s, 3H), 1.88-1.75 (m, 2H), 1.58 (d, J ¼ 5.9 Hz, 3H), 1.06 (t, J ¼ 6.2 Hz, 3H) 13. C NMR (100 MHz, CDCl 3 ): d 172.9, 169.5, 162.1, 160.5, 156.0, 149.1, 128.4, 121.4, 117.9, 117.5, 115.7, 99.2, 70.1, 42.3, 23.3, 22.7, 19.6, 10.6.…”