Modified fatty acids and their possible therapeutic targets in malignant diseases.
Fatty acids and other lipids have multiple roles in the cell, functioning as structural components, participating in intracellular signalling and serving as metabolic fuel. Various compounds that influence cellular lipid metabolism can reduce the growth of malignant cells, and dietary as well as pharmacological strategies for modulating lipid metabolism have therefore been suggested as possible approaches for cancer prevention and treatment. By chemically modifying fatty acids (e.g., butyrates, retinoids), new potential anticancer agents have been produced that possess increased metabolic stability and more specific and potent biological activity compared to the natural fatty acids. Possible therapeutic targets for such modified fatty acids include: i) Histone deacetylase; ii) nuclear hormone receptors (retinoid receptors), peroxisome proliferator-activated receptors; iii) cyclooxygenase-2; iv) intracellular signalling involving protein farnesylation and Ras activation; and v) various mitochondrial functions. Although several fatty acid derivatives have been thoroughly investigated in experimental models, clinical data on toxicity and pharmacological interactions are not available for the majority of these agents. However, several promising novel compounds are now being evaluated in preclinical and early clinical studies, and future research will hopefully reveal new formulations and therapy schedules that will improve the outcome of patients with malignant disorders.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002986:Clinical Trials as Topic; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D015777:Eicosanoids / Q000378:metabolism; D005227:Fatty Acids / Q000737:chemistry / Q000378:metabolism*; D011905:Genes, ras; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D008954:Models, Biological; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000517:prevention & control; D017368:Protein Prenylation / Q000187:drug effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000502:physiology
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D015777:Eicosanoids; D005227:Fatty Acids; D056572:Histone Deacetylase Inhibitors; D009363:Neoplasm Proteins; D018160:Receptors, Cytoplasmic and Nuclear