期刊
ADVANCED DRUG DELIVERY REVIEWS
卷 159, 期 -, 页码 245-293出版社
ELSEVIER
DOI: 10.1016/j.addr.2020.07.013
关键词
Fatty acids; Fatty acid synthesis; Lipid uptake; Lipid droplets; De novo lipogenesis; Membrane lipids; Reactive oxygen species; Lipidomics
资金
- EU Interreg grant [V-A EMR23 EURLIPIDS]
- Research Foundation-Flanders (FWO)
- Stichting tegen Kanker, Kom op tegen Kanker
- Movember Foundation/Prostate Cancer Foundation of Australia
- Prostate Cancer Foundation of Australia [2711]
- Cancer Council South Australia Beat Cancer Project [PRF1117]
- NIH [RO1CA131945, R01CA187918, RO1CA58961]
- Norris Cotton Cancer Center
- Dartmouth College Norris Cotton Cancer Center [P30CA023108]
- DoD [PC160357, DoD PC180582, P50CA211024]
- Prostate Cancer Foundation
- Stichting tegen Kanker
- Kom op tegen Kanker
- Movember Foundation/Prostate Cancer Foundation of Australia (MRTA3)
- KU Leuven [C16/15/073, C32/17/052]
With the advent of effective tools to study lipids, including mass spectrometry-based lipidomics, lipids are emerging as central players in cancer biology. Lipids function as essential building blocks for membranes, serve as fuel to drive energy-demanding processes and play a key role as signaling molecules and as regulators of numerous cellular functions. Not unexpectedly, cancer cells, as well as other cell types in the tumor microenvironment, exploit various ways to acquire lipids and extensively rewire their metabolism as part of a plastic and context-dependent metabolic reprogramming that is driven by both oncogenic and environmental cues. The resulting changes in the fate and composition of lipids help cancer cells to thrive in a changing microenvironment by supporting key oncogenic functions and cancer hallmarks, including cellular energetics, promoting feedforward oncogenic signaling, resisting oxidative and other stresses, regulating intercellular communication and immune responses. Supported by the close connection between altered lipid metabolism and the pathogenic process, specific lipid profiles are emerging as unique disease biomarkers, with diagnostic, prognostic and predictive potential. Multiple preclinical studies illustrate the translational promise of exploiting lipid metabolism in cancer, and critically, have shown context dependent actionable vulnerabilities that can be rationally targeted, particularly in combinatorial approaches. Moreover, lipids themselves can be used as membrane disrupting agents or as key components of nanocarriers of various therapeutics. With a number of preclinical compounds and strategies that are approaching clinical trials, we are at the doorstep of exploiting a hitherto underappreciated hallmark of cancer and promising target in the oncologist's strategy to combat cancer. (C) 2020 The Author(s). Published by Elsevier B.V.
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