Fatty acid addiction in cancer: A high-fat diet directly promotes tumor growth through fatty acid oxidation

Tumor growth promoted by a high-fat diet (HFD) was completely reversed by inhibiting fatty acid oxidation (FAO). The promotion of tumors by an HFD is known to result from the indirect effects of sex hormones, leptin, and adipokines such as insulin-like growth factor-1 (IGF-1) on cancer cells. However, even though HFD notably increased blood levels of IGF-1, knocking down the carnitine-acylcarnitine carrier (CAC) to inhibit FAO completely reversed the tumor-promoting effects in pancreatic cancer cells, accompanied by a significant decrease in ATP production. When ATP levels dropped due to FAO inhibition in cancer cells, mTOR - a key regulator of survival - became inactive, leading to reduced cell viability and increased cell death. This shows that HFD promotes cancer cell growth by supplying more calories through FAO, indicating that cancer is addicted to fatty acids. This review emphasizes the crucial role of cancer-specific FAO in tumor growth and proposes potential new therapeutic strategies targeting various FAO enzymes as innovative anti-cancer treatments.