ATP citrate lyase (ACLY), an important enzyme involved in lipid biogenesis linked with glucose
metabolism, catalyzes the conversion of citrate to oxaloacetic acid (OAA) and acetyl-CoA. The obtained
acetyl-CoA is required for lipid synthesis during membrane biogenesis, as well as for histone acetylation
reactions to regulate the expression of certain proteins in aberrantly proliferating cancer cells.
Studies have shown a role for ACLY in tumorigenesis whereby increased levels of the enzyme leads to
increased metabolic activity via activation of Akt signaling. Increasing lines of evidence suggest that enzymes
involved in lipid biogenesis play a significant role in cancer cell proliferation and progression. In many cancer
types such as glioblastoma, colorectal cancer, breast cancer, non-small cell lung cancer, hepatocellular carcinoma etc., the
level of ACLY has been found to be quite high as compared to normal cells. Cancer cell growth related to overexpression
of ACLY can be inhibited by using chemical inhibitors or by the knockdown of ACLY gene. Inhibition of ACLY leads to
changes in cancer cell metabolism that promotes tumor growth and proliferation. This review summarizes the role of
ACLY in cancer development and its inhibitors in cancer treatment.