发明公开
EP1728510A2 Treating cancer by increasing intracellular malonyl coA levels 审中-公开
Behandlung von Krebs durchErhöhungdes Malonyl-coA-Spiegels

Treating cancer by increasing intracellular malonyl coA levels
摘要:
This invention describes a method to kill cancer cells by acute elevation of cellular malonyl Coenzyme A (Malonyl CoA) which leads to apoptosis. Elevation of malonyl CoA may be induced by inhibition of fatty acid synthase (FAS), or by other manipulation of fatty acid metabolism tht does not involve inhibition of FAS. Alternatively, growth of tumor cells may be induced by a combination of effects including FAS inhibition in conjunction with other interventions which affect fatty acid metabolism, including inhibition of camitine palmitoyltransferase-1 (CPT-1). Any combination of drugs which produces an analogous physiologic effect(s) may be expected to lead to the same effect on susceptible tumor cells. For example, combination therapy with drug(s) that inhibit the fatty acid synthesis by inhibiting acetyl CoA carboxylase (the first enzyme in the fatty acid synthesis pathway) and drug(s) that inhibit CPT-1 may be expected to induce apoptosis in tumor cells. Therefore, this invention encompasses any method to systemically modify fatty acid metabolism in cancer cells including but not limited to direct inhibition of CPT-1 through small molecule inhibitors such as etomoxir, as well as inhibition of CPT-1 incidental to increasing the level of malonyl CoA in cancer cells.
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