Cancer treatment including glycolytic inhibitors

Abstract

Glycolytic inhibitors are useful in the treatment of solid tumors by attacking anaerobic cells at the center on the tumor. 2-deoxyglucose, oxamate and various analogs thereof are identified as having a natural selective toxicity toward anaerobic cells, and will significantly increase the efficacy of standard cancer chemotherapeutic and radiation regiments as well as new protocols emerging with anti-angiogenic agents.

Description

FIELD AND BACKGROUND OF THE INVENTION The present invention relates, in general, to compositions and methods aimed at effectively treating anaerobic tumor cells with inhibitors of glycolysis. It also extends to novel and useful methods and compositions for treating aerobic tumor cells with inhibitors of oxidative phosphorylation in combination with glycolytic inhibitors. Inhibiting oxidative phosphorylation to convert aerobic tumor cells to anaerobic cells, hypersensitizes them to glycolytic inhibitors. U.S. patents that are relevant to the compositions and methods of the present invention are: U.S. Pat. Nos. 4,840,939 and 4,684,627, both for a treatment of cancer with phlorizin and its derivatives; U.S. Pat. No. 4,683,222 for N-glycosylated carboxamide derivatives and their use for influencing the body's inherent defenses; and U.S. Pat. No. 4,420,489 for sugars with sulfur replacing the ring oxygen atom as antiradiation agents. U.S. Pat. No. 4,840,939 is also relevant for its dis...

AI Technical Summary

Benefits of technology

The present invention is based on the discovery that glycolytic inhibitors and analogs thereof, are selectively toxic to tumor cells which are metabolizing anaerobically. Thus, in conjunction with standard chemotherapy and / or radiation which is focused on aerobic, fast-growing cells, which we will here refer to collectively and individually as “aerobic treatment”, use of these inhibitors will add to the efficacy of cancer treatment by selectively killing the anaerobically slow-growing tumor cells found at the inner core of solid tumors which are usually the most resistant and consequently the most difficult to eradicate using aerobic treatments.

Problems solved by technology

Although Warburg originally proposed that tumor cells depend less on mitochondrial function for ATP production and more on glycolysis than normal cells, there has been no definitive data to date to confirm this hypothesis.

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