The activation of the de novo fatty acid synthesis pathway is not only observed in tumors but also may be required for malignant progression (65, 72, 73). For example, elevated levels of FASN, the enzyme catalyzing the synthesis of palmitate and thereby required for long chain and unsaturated fatty acid synthesis, are correlated with poor prognosis in breast cancer patients (65, 72). Increases in FASN activity and expression are observed early in cancer development and correlate with cancer progression, while high FASN levels correlate with more aggressive malignant phenotypes (65). Inhibiting key enzymes involved in fatty acid synthesis, including FASN, ACC, and ACLY, with small molecules or knockdowns reduces cell proliferation, induces the apoptosis of cancer cells, and decreases the growth of human tumors grown as mouse xenografts (65, 71, 74–77).
