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Adipocyte and lipid metabolism in cancer drug resistance
Yihai Cao
Yihai Cao
Published July 2, 2019
Citation Information: J Clin Invest. 2019;129(8):3006-3017. https://doi.org/10.1172/JCI127201.
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Review

Adipocyte and lipid metabolism in cancer drug resistance

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Abstract

Development of novel and effective therapeutics for treating various cancers is probably the most congested and challenging enterprise of pharmaceutical companies. Diverse drugs targeting malignant and nonmalignant cells receive clinical approval each year from the FDA. Targeting cancer cells and nonmalignant cells unavoidably changes the tumor microenvironment, and cellular and molecular components relentlessly alter in response to drugs. Cancer cells often reprogram their metabolic pathways to adapt to environmental challenges and facilitate survival, proliferation, and metastasis. While cancer cells’ dependence on glycolysis for energy production is well studied, the roles of adipocytes and lipid metabolic reprogramming in supporting cancer growth, metastasis, and drug responses are less understood. This Review focuses on emerging mechanisms involving adipocytes and lipid metabolism in altering the response to cancer treatment. In particular, we discuss mechanisms underlying cancer-associated adipocytes and lipid metabolic reprogramming in cancer drug resistance.

Authors

Yihai Cao

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Figure 3

The mechanism of adipocyte metabolic reprogramming in antiangiogenic drug resistance.

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The mechanism of adipocyte metabolic reprogramming in antiangiogenic dru...
Treatment of tumors with antiangiogenic drugs reduces the tumor vascular density, leading to tissue hypoxia. Hypoxia triggers lipolysis in tumor-infiltrating and peritumoral CAAs to produce excessive FFAs. Hypoxia also upregulates the expression levels of CD36, the fatty acid translocase or receptor, in cancer cells to increase FFA uptake. Within tumor cells, FFA through the β-oxidation pathway is metabolized to produce ATP that supports tumor cell proliferation and migration in the presence of a minimal number of microvessels. This mechanism explains in part how CAAs contribute to antiangiogenic drug resistance.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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