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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 2

Mechanistic principles underlying cancer treatment and obesity-associated treatment resistance.

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Mechanistic principles underlying cancer treatment and obesity-associate...
(A) Mechanistic principles of cancer drugs. Conventional treatment approaches, including chemotherapeutics and radiation therapy, indistinguishably target malignant and nonmalignant cells in the tumor microenvironment and elsewhere in the body. Numerous targeted therapeutics targeting cancer cells have been developed, such as trastuzumab. Other targeted therapeutics, including antiangiogenic drugs, immune regulators, and antiinflammatory and antifibrotic drugs, aim to interfere with or enhance the interaction between nonmalignant cells and cancer cells. (B) Possible mechanisms of obese adipocytes in contributing to anticancer resistance. Obese adipocytes may have altered metabolism, pharmacokinetics, expression of tumor cell survival factors, immune cell functions, vascular functions, and drug distribution to affect anticancer drug responses. These alterations often lead to the development of resistance to cancer drugs.

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

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