etc-1002 and Neoplasms

Cancer cells rely on several metabolic pathways such as lipid metabolism to meet the increase in energy demand, cell division, and growth and successfully adapt to challenging environments. Fatty acid synthesis is therefore commonly enhanced in many cancer cell lines. Thus, relevant efforts are being made by the scientific community to inhibit the enzymes involved in lipid metabolism to disrupt cancer cell proliferation. We review the rapidly expanding body of inhibitors that target lipid metabolism, their side effects, and current status in clinical trials as potential therapeutic approaches against cancer. We focus on their molecular, biochemical and structural properties, selectivity and effectiveness and discuss their potential role as antitumor drugs.

Topics: Antineoplastic Agents; Azetidines; Dicarboxylic Acids; Enzyme Inhibitors; Fatty Acid Synthases; Fatty Acids; Humans; Lipid Metabolism; Lipogenesis; Neoplasms; Nitriles; Pyrazoles

ATP citrate lyase is an enzyme in the cholesterol-biosynthesis pathway upstream of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the target of statins. Whether the genetic inhibition of ATP citrate lyase is associated with deleterious outcomes and whether it has the same effect, per unit decrease in the low-density lipoprotein (LDL) cholesterol level, as the genetic inhibition of HMGCR is unclear.. We constructed genetic scores composed of independently inherited variants in the genes encoding ATP citrate lyase (. A total of 654,783 participants, including 105,429 participants who had major cardiovascular events, were included in the study. The. Genetic variants that mimic the effect of ATP citrate lyase inhibitors and statins appeared to lower plasma LDL cholesterol levels by the same mechanism of action and were associated with similar effects on the risk of cardiovascular disease per unit decrease in the LDL cholesterol level. (Funded by Esperion Therapeutics and others.).

Topics: ATP Citrate (pro-S)-Lyase; Cardiovascular Diseases; Cholesterol, LDL; Diabetes Mellitus; Dicarboxylic Acids; Fatty Acids; Female; Genetic Predisposition to Disease; Humans; Hydroxymethylglutaryl CoA Reductases; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Hypolipidemic Agents; Lipoproteins; Male; Membrane Proteins; Membrane Transport Proteins; Mendelian Randomization Analysis; Middle Aged; Neoplasms; Odds Ratio; Risk; Triglycerides