Internal medicine

Tumor microenvironment

Obesity

Biology

Cancer

Endocrinology

Paleontology

Polyunsaturated fatty acid

Insulin resistance

Fatty acid metabolism

Context (archaeology)

Lipid metabolism

Metabolism

Lipotoxicity

Cancer research

Fatty acid

Biochemistry

Medicine

Beta oxidation

Cancer cell

Nature reviews. Cancer

Fatty acid metabolism is known to support tumorigenesis and disease progression as well as treatment resistance through enhanced lipid synthesis, storage and catabolism. More recently, the role of membrane fatty acid composition, for example, ratios of saturated, monounsaturated and polyunsaturated fatty acids, in promoting cell survival while limiting lipotoxicity and ferroptosis has been increasingly appreciated. Alongside these insights, it has become clear that tumour cells exhibit plasticity with respect to fatty acid metabolism, responding to extratumoural and systemic metabolic signals, such as obesity and cancer therapeutics, to promote the development of aggressive, treatment-resistant disease. Here, we describe cellular fatty acid metabolic changes that are connected to therapy resistance and contextualize obesity-associated changes in host fatty acid metabolism that likely influence the local tumour microenvironment to further modify cancer cell behaviour while simultaneously creating potential new vulnerabilities. This Review discusses mechanistic links between fatty acid metabolism in cancer cells and disease behaviour and therapy resistance, integrating obesity-associated changes that modify cancer cell behaviour.

Tumour fatty acid metabolism in the context of therapy resistance and obesity